PROG:
 
1
UNIQUE IDENTIFIER         NIH/00632
PROTOCOL ID NUMBERS       NINDS 93 N-30
PROTOCOL TITLE            The Efficacy of Oral Levocarnitine
                          (L-Carnitine) Therapy on Zidovudine-Induced
                          Myopathy: A Double-Blind, Placebo-Controlled
                          Trial.
VERSION NUMBER & DATE     (940520)
TRIAL CATEGORY            Neurologic Manifestations
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Dulakas M
PROTOCOL CHAIRS           CO-CHAIR  Cupler E
GENERAL DESCRIPTION       PURPOSE: To evaluate the effects of
                          levocarnitine (L-carnitine) on zidovudine
                          (AZT)-induced myopathy in patients currently
                          receiving AZT therapy for HIV infection.
GENERAL DESCRIPTION       RATIONALE: Some HIV-infected patients
                          receiving AZT therapy develop a
                          medication-induced muscle disease called
                          myopathy. Current recommendations usually are
                          to decrease or discontinue AZT therapy, but
                          since AZT is the most effective treatment of
                          HIV infection currently available, a therapy
                          for the side effect of muscle disease would
                          be highly beneficial.
GENERAL DESCRIPTION       METHODOLOGY: Patients who are receiving AZT
                          and experiencing myopathy are randomized to
                          receive either oral L-carnitine or placebo
                          thrice daily for 6 months. Patients will
                          undergo two muscle biopsies in addition to
                          EMG and nerve conduction studies, blood
                          studies, and muscle strength and function
                          assessments. A total of five clinic visits
                          (visits for screening, for the initial
                          biopsy, and at months 2, 4, and 6) will be
                          required. Patients will also need to complete
                          questionnaires at home every 2 weeks. At the
                          end of 6 months, patients on the placebo arm
                          may receive 6 months of L-carnitine on an
                          optional basis, provided benefit was shown.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940520)
DISEASE STUDIED           Myopathy.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Current AZT therapy for HIV
                          infection and intending to remain on AZT
                          therapy for the duration of the study. 2.
                          Biopsy-proven AZT-induced myopathy. Clinical
                          signs of AZT-induced myopathy may include
                          muscle weakness, muscle shrinkage, fatigue,
                          decreased endurance, muscle pain, abnormal
                          elevation of creatine kinase, or evidence of
                          muscle disease by EMG.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: OPEN patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 6
                          months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Current AZT therapy for HIV
                          infection. 2. Diagnosis of AZT-induced
                          myopathy. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Prior AZT.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: AZT.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0211  Levocarnitine
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Drug or placebo
                          thrice daily for at least 6 months
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 months.
SUPPORTING AGENCY         National Institute of Neurological Disorders
                          & Stroke.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Carnitine/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Muscles/DRUG EFFECTS/*PATHOLOGY
MESH HEADING              Muscular Diseases/*CHEMICALLY INDUCED/
                          COMPLICATIONS/PATHOLOGY
MESH HEADING              Zidovudine/ADVERSE EFFECTS
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940520
ENTRY MONTH               9406
MARYLAND                  National Institute of Neurological Disorders
                          & Stroke 9000 Rockville Pike / Bldg 10 Room
                          4N248 Bethesda, MD 20892 Contact: Dr Edward
                          Cupler (301) 402-1931 OPEN / USA Accrual
                          940520.
 
2
UNIQUE IDENTIFIER         NIH/00600
PROTOCOL ID NUMBERS       NIAID WIHS
PROTOCOL TITLE            Women's Interagency HIV Study (WIHS).
VERSION NUMBER & DATE     (940621)
TRIAL CATEGORY            Epidemiology
GENERAL DESCRIPTION       PURPOSE: To define, in women, the following:
                          the spectrum and course of HIV infection; the
                          pattern and rate of change of immunologic
                          markers in women and the relationship of
                          these changes to other immunologic and
                          virologic parameters and to the clinical
                          manifestations of HIV; and the various
                          factors that may influence HIV disease
                          progression. Methodology: Study visits are
                          scheduled for every 6 months.
GENERAL DESCRIPTION       METHODOLOGY: Study visits are scheduled for
                          every 6 months.
PROTOCOL PHASE            Epidemiology
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (940930)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Participants must meet the following
                          criteria: o HIV-infected women OR o
                          HIV-uninfected women who are at high risk for
                          HIV because of multiple sexual partners,
                          injection of drugs, or has a sex partner who
                          is at high risk, either through multiple sex
                          partners or injection of drugs.
ELIGIBILITY               HIV Seropositive. HIV Seronegative.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Prospective
PROTOCOL DETAILS          STUDY INTENT: Epidemiology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 2500 patients. (2000
                          HIV-positive women; 500 HIV-seronegative
                          women).
PROTOCOL DETAILS          STUDY DURATION: 4 years (until July 1997).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants meet
                          the following criteria: 1. HIV infected women
                          OR uninfected women who are at high risk for
                          HIV. 2. Willing to be retested for HIV
                          infection for this study. 3. Able to complete
                          interview in English or Spanish. 4. Able to
                          travel to and from site clinic and
                          participate in a baseline visit as an
                          outpatient. 5. Willing to have blood drawn.
                          NOTE: Patients must be 18 years of age for
                          enrollment at certain sites. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: Non-applicable percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: Non-applicable g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: Non-applicable cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: Non-applicable platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CD4/CD8 RATION: Non-applicable.
PATIENT INCLUSION CRIT.   BILIRUBIN: Non-applicable mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): Non-applicable.
PATIENT INCLUSION CRIT.   SGPT(ALT): Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE: Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: Non-applicable ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: Non-applicable.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   SEX: MALE
SUPPORTING AGENCY         NIAID Epidemiology Branch.
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Human
MESH HEADING              Middle Age
LAST REVISION DATE        940930
ENTRY MONTH               9410
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          940303 ACTU: 1201.
CALIFORNIA                University of California / San Francisco Box
                          1352 / 400 Parnassus Avenue / AC-16 San
                          Francisco, CA 94143-0422 Contact: Rose Katsis
                          (415) 476-9356 OPEN 940303.
DISTRICT OF COLUMBIA      Georgetown University Medical Center 110
                          Kober-Cogan Bldg / 3800 Reservoir Road N.W.
                          Washington, DC 20007 Contact: Barbara Lewis
                          (202) 784-2687 OPEN 940303.
ILLINOIS                  Chicago Consortium 1835 West Harrison / CCSN
                          Room 1245 Chicago, IL 60612 Contact: Kathleen
                          Weber (312) 572-3715 Contact: Dr Mardge Cohen
                          OPEN 940303.
NEW YORK                  Bronx - Lebanon Hospital Center 1309 Fulton
                          Avenue / 4th Floor Bronx, NY 10456 Contact:
                          Sara Back (718) 901-8980 OPEN 940303.
NEW YORK                  SUNY at Brooklyn 450 Clarkson Avenue
                          Brooklyn, NY 11203 Contact: Susan Holman
                          (718) 270-1819 OPEN 940303.
 
3
UNIQUE IDENTIFIER         NIH/00615
PROTOCOL ID NUMBERS       NIAID VEU 018
PROTOCOL TITLE            A Phase I Safety and Immunogenicity Trial of
                          UBI Microparticulate Monovalent HIV-1 MN
                          Peptide Immunogen in HIV-1 Seronegative Human
                          Subjects.
VERSION NUMBER & DATE     (940912)
TRIAL CATEGORY            Vaccines
TRIAL CATEGORY            HIV Negative
PROTOCOL CHAIRS           CHAIR  Lambert J
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and
                          immunogenicity of a new microparticulate
                          formulation of an HIV-1 MN PND peptide for
                          oral administration in healthy, HIV-1
                          seronegative adult volunteers at low risk for
                          infection.
GENERAL DESCRIPTION       RATIONALE: Vaccine formulations of synthetic
                          peptides adsorbed to alum may not provide
                          other requisite characteristics of an
                          effective HIV vaccine, such as induction of
                          mucosal immunity, production of cytotoxic T
                          cells, and ease of administration. An oral
                          microparticulate vaccine containing a
                          prototype synthetic peptide has been
                          developed. The microparticles can be degraded
                          over time, inducing both secretory and
                          systemic immune responses.
GENERAL DESCRIPTION       METHODOLOGY: Twelve volunteers per dose
                          regimen will receive oral microparticulate
                          multivalent HIV-1 peptide vaccine at months
                          0, 1, and 6, either as 1 mg daily for 3 days
                          or 3 mg in a single dose. Additionally, four
                          volunteers per regimen will receive placebo.
                          Volunteers are followed for 1 year. They will
                          be contacted once or twice yearly for 5 years
                          to check on health status.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Healthy.
DISEASES STATUS           Subjects have the following conditions: 1.
                          Normal history and physical exam. 2. HIV
                          negative by ELISA within 8 weeks of study
                          entry. 3. Absolute CD4 count >= 400
                          cells/mm3. 4. Normal urine dipstick with
                          esterase and nitrite. 5. Lower or
                          intermediate risk sexual behavior.
ELIGIBILITY               HIV Seronegative.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled
PROTOCOL DETAILS          STUDY INTENT: Vaccine prophylaxis,
                          Immunology, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 32 patients. (16 vaccinees
                          at each of two participating sites)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 52 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 26/32 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Subjects must
                          have: 1. Normal history and physical exam. 2.
                          HIV negativity by ELISA within 8 weeks of
                          study entry. 3. Absolute CD4 count >= 400
                          cells/mm3. 4. Normal urine dipstick with
                          esterase and nitrite. 5. Lower or
                          intermediate risk sexual behavior. NOTE: No
                          more than 10 percent of subjects may be over
                          50 years of age. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 34 percent. (women); >= 38
                          percent (men).
PATIENT INCLUSION CRIT.   PLATELET COUNT: 150000 - 550000
                          platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3. ( 400
                          - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 1.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: WBC >= 3500 cells/mm3 with normal
                          differential. Total lymphocytes >= 800
                          cells/mm3.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Subjects with the
                          following prior conditions are excluded: 1.
                          History of immunodeficiency, chronic illness,
                          or autoimmune disease. 2. History of
                          anaphylaxis or other serious reactions to
                          vaccines. 3. History of inflammatory
                          gastrointestinal disease, celiac disease, or
                          intestinal malignancy. 4. History of acute
                          gastroenteritis within the past month or
                          gastrointestinal surgery within the past
                          year. 5. History of cancer unless there has
                          been surgical excision with reasonable
                          assurance of cure. 6. History of serious
                          allergic reaction. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Identifiable higher risk
                          behavior for HIV infection, including the
                          following: 1. History of injection drug use
                          within the past 12 months. 2. Higher risk
                          sexual behavior as defined by the AVEG.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Blood products or
                          immunoglobulin within the past 6 months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. History of
                          immunosuppressive medications. 2. Live
                          attenuated vaccines within 60 days prior to
                          study entry (NOTE: Medically indicated
                          subunit or killed vaccines, e.g., influenza
                          or pneumococcal, are not exclusionary, but
                          should not be given within 2 weeks of HIV
                          immunization). 3. Experimental agents within
                          30 days prior to study entry. 4. Prior HIV
                          vaccines.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Subjects with the following
                          symptoms or conditions are excluded: 1.
                          Positive hepatitis B surface antigen. 2.
                          Medical or psychiatric condition (such as
                          psychosis or suicidal tendencies) or
                          occupational responsibilities that preclude
                          study compliance. 3. Active syphilis. NOTE:
                          Subjects whose serology is documented to be a
                          false positive or due to a remote (> 6
                          months) treated infection are eligible. 4.
                          Active tuberculosis. NOTE: Subjects with a
                          positive PPD and normal chest x-ray showing
                          no evidence of TB and not requiring isoniazid
                          therapy are eligible.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unavailable for 52 weeks of
                          follow-up.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0212  Microparticulate Monovalent
                          HIV-1 Peptide Vaccine
MANUFACTURERS             Drug 1: United Biomedical Inc 25 Davids Drive
                          Hauppauge, NY 11788 Contact: Dr Bruce Forrest
                          (516) 273-2828.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 mg daily for 3
                          days OR 3 mg in a single dose (or placebo) at
                          months 0, 1, and 6
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 1 mg vials
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (VEU), United Biomedical Inc.
MESH HEADING              Administration, Oral
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              HIV Infections/*PREVENTION & CONTROL
MESH HEADING              HIV-1/*IMMUNOLOGY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Vaccines, Synthetic/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/IMMUNOLOGY
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
LAST REVISION DATE        941207
ENTRY MONTH               9407
MARYLAND                  Johns Hopkins University / Center for
                          Immunization Research Hampton House / 624
                          North Broadway Baltimore, MD 21205 Contact:
                          Dr Jack Lambert (410) 955-7283 OPEN 940629.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 575 Elmwood Avenue Rochester, NY 14642
                          Contact: Unspecified (716) 275-5744 Contact:
                          (716) 275-6561 OPEN 940629.
 
4
UNIQUE IDENTIFIER         NIH/00635
PROTOCOL ID NUMBERS       NIAID VEU 016A
PROTOCOL TITLE            A Phase I, Multicenter, Randomized,
                          Double-Blind, Placebo-Controlled HIV-1
                          Vaccine Trial to Evaluate the Safety and
                          Immunogenicity of MN Recombinant Soluble
                          gp120/HIV-1 (rsgp120/HIV-1) (Genentech) in
                          Combination With QS21 Adjuvant and/or Alum in
                          Healthy Adults.
VERSION NUMBER & DATE     (940610)
TRIAL CATEGORY            Vaccines
TRIAL CATEGORY            HIV Negative
PROTOCOL CHAIRS           CHAIR  McElrath J
GENERAL DESCRIPTION       PURPOSE: To extend the evaluation of safety
                          and immunogenicity of MN recombinant soluble
                          gp120/HIV-1 (MN rsgp120/HIV-1) in combination
                          with QS21 with or without alum and on two
                          different vaccination schedules.
GENERAL DESCRIPTION       RATIONALE: Recent animal studies indicate
                          that immunizing with MN rsgp120/HIV-1 in
                          combination with QS21 on a 0, 1, 2 month
                          schedule results in a more rapid rise in
                          binding and neutralizing antibody response
                          than on a 0, 1, 6 month schedule. Such an
                          effect may be particularly desirable in
                          vaccine delivery. This study compares these
                          two delivery schedules using the unadjuvanted
                          vaccine formulation rsgp120/HIV-1 with or
                          without addition of alum.
GENERAL DESCRIPTION       METHODOLOGY: Healthy volunteers (20 per
                          group) receive MN rsgp120/HIV-1 (300 or 0
                          mcg) in combination with QS21 (100 mcg),
                          either with or without alum, at 0, 1, and 2
                          months or 0, 1, and 6 months. For both
                          vaccination schedules, an additional five
                          volunteers receive only vehicle with alum.
                          The 0 mcg antigen groups are included
                          primarily as negative controls. Subjects may
                          be contacted for follow-up on health status
                          once or twice yearly for at least 5 years.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Healthy.
DISEASES STATUS           Subjects have the following conditions: 1.
                          Normal history and physical exam, with no
                          significant abnormalities. 2. Negative for
                          HIV by ELISA within 8 weeks of immunization.
                          3. Absolute CD4 count >= 400 cells/mm3. 4.
                          Normal urine dipstick with esterase and
                          nitrite.
ELIGIBILITY               HIV Seronegative.
OTHER PROTOCOL NUMBERS    IND BB5045
STUDY DESIGN              Randomized; Double-Blind; Multicenter;
                          Placebo-Controlled; Drug Tolerance; Dose
                          Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Vaccine
                          prophylaxis, Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: VEU 017 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately
                          12 months, with possible follow-up once or
                          twice yearly for at least 5 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 110/VEU 017 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Subjects must
                          have: 1. Normal history and physical exam. 2.
                          HIV negative by ELISA within 8 weeks of
                          immunization. 3. Absolute CD4 count >= 400
                          cells/mm3. 4. Normal urine dipstick with
                          esterase and nitrite. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 34 percent. (women); >= 38
                          percent (men).
PATIENT INCLUSION CRIT.   PLATELET COUNT: 150000 - 550000
                          platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3. ( 400
                          - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 1.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: WBC >= 3500 cells/mm3 with normal
                          differential. Total lymphocytes >= 800
                          cells/mm3.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Subjects with the
                          following prior conditions are excluded: 1.
                          History of immunodeficiency, autoimmune
                          disease, or use of immunosuppressive
                          medications. 2. History of anaphylaxis or
                          other serious adverse reactions to vaccines.
                          3. History of allergy to thimersol. 4.
                          History of serious allergic reaction to any
                          substance, requiring hospitalization or
                          emergent medical care (e.g., Steven-Johnson
                          syndrome, bronchospasm, or hypotension). 5.
                          Prior psychiatric condition (such as history
                          of suicide attempts or past psychosis) that
                          precludes compliance. 6. History of cancer
                          unless there has been surgical excision that
                          is considered to have achieved cure. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Subjects are NOT excluded on
                          the basis of HIV risk behaviors, but
                          AVOIDANCE of any activity that may expose
                          subject to HIV (e.g., unprotected sex or
                          needle sharing) is STRONGLY RECOMMENDED.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Receipt of blood
                          products or immunoglobulin within the past 6
                          months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Live
                          attenuated vaccines within 60 days prior to
                          study entry. (NOTE: Medically indicated
                          subunit or killed vaccines, such as influenza
                          or pneumococcal, are allowed but should be
                          given at least 2 weeks prior to HIV
                          immunizations.) 2. Experimental agents within
                          30 days prior to study entry. 3. Prior HIV
                          vaccines.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Subjects with the following
                          symptoms or conditions are excluded: 1.
                          Hepatitis B surface antigen. 2. Medical or
                          psychiatric condition (such as recent
                          suicidal ideation or present psychosis) that
                          precludes compliance. 3. Occupational
                          responsibilities that preclude compliance. 4.
                          Active syphilis. NOTE: Subjects with serology
                          documented to be false positive or due to a
                          remote (> 6 months) treated infection are
                          eligible. 5. Active tuberculosis. NOTE:
                          Subjects with a positive PPD and normal chest
                          x-ray showing no evidence of TB and not
                          requiring isoniazid therapy are eligible.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unavailable for 18 months of
                          follow-up.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0153  rgp120/HIV-1MN
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0178  QS-21
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0172  Aluminum hydroxide
MANUFACTURERS             Drug 1: Genentech Incorporated 460 Point San
                          Bruno Boulevard South San Francisco, CA 94080
                          Contact: Professional Services (800)
                          821-8590.
MANUFACTURERS             Drug 2: Genentech Incorporated 460 Point San
                          Bruno Boulevard South San Francisco, CA 94080
                          Contact: Professional Services (800)
                          821-8590.
MANUFACTURERS             Drug 3: Genentech Incorporated 460 Point San
                          Bruno Boulevard South San Francisco, CA 94080
                          Contact: Professional Services (800)
                          821-8590.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 0 or 300 mcg at
                          months 0, 1, and 2 or months 0, 1, and Drug
                          2: 0 or 100 mcg at months 0, 1, and 2 or
                          months 0, 1, and Drug 3: Administered with
                          vaccine in selected subject cohorts amonths
                          0, 1, and 2 or months 0, 1, and 6
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Intramuscular. Drug 3: Intramuscular
OTHER TREATMENT INFO.     END POINT: Safety, immunogenicity.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (VEU).
MESH HEADING              Adjuvants, Immunologic
MESH HEADING              Adult
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Envelope Protein gp120/*IMMUNOLOGY
MESH HEADING              HIV Infections/*PREVENTION & CONTROL
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Vaccines, Synthetic
CAS REGISTRY NUMBER       0 (HIV Envelope Protein gp120)
CAS REGISTRY NUMBER       0 (Adjuvants, Immunologic)
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
LAST REVISION DATE        941207
ENTRY MONTH               9406
MARYLAND                  Johns Hopkins University / Center for
                          Immunization Research Hampton House Rm 125 /
                          624 North Broadway Baltimore, MD 21205
                          Contact: Karen Charron (410) 955-7283 OPEN
                          940504 ACTU: 6002.
MISSOURI                  St Louis University School of Medicine / Sec
                          Inf Dis 1402 South Grand Boulevard St Louis,
                          MO 63104 Contact: Dr Robert B Belshe (314)
                          577-8648 Contact: Heidi Israel (314) 577-8649
                          OPEN 940602 ACTU: 6007.
NEW YORK                  University of Rochester Medical Center Box
                          689 / Room 36209 / 601 Elmwood Avenue
                          Rochester, NY 14642 Contact: Dr Michael
                          Keefer (716) 275-0810 OPEN 940602 ACTU: 6005.
 
5
UNIQUE IDENTIFIER         NIH/00490
PROTOCOL ID NUMBERS       NIAID VEU 014
PROTOCOL TITLE            A Multicenter, Randomized,
                          Placebo-Controlled, Double-Blind Trial to
                          Evaluate the Safety and Immunogenicity of a
                          Recombinant Vaccinia-HIV-1 IIIB Env/Gag/Pol
                          Vaccine (TBC-3B).
VERSION NUMBER & DATE     (940601)
TRIAL CATEGORY            Vaccines
TRIAL CATEGORY            HIV Negative
PROTOCOL CHAIRS           CHAIR  Keefer M
GENERAL DESCRIPTION       PURPOSE: To evaluate, in healthy HIV-1
                          seronegative vaccinia-immune and
                          vaccinia-naive volunteers, the safety and
                          immunogenicity of an HIV-1 candidate vaccine
                          (TBC-3B) consisting of a live recombinant
                          vaccinia virus expressing the env, gag, and
                          pol genes of HIV-1 IIIB strain. To evaluate
                          the potential of boosting with one of a
                          variety of HIV-1 recombinant subunit,
                          peptide, or pseudovirion vaccines, if
                          available, to augment the immune responses of
                          the vaccinees.
GENERAL DESCRIPTION       RATIONALE: Antigenic drift, defined as the
                          genetic variation of the HIV-1 envelope gene
                          that results in antigenic variation during
                          natural infection, may confound attempts to
                          achieve protective immunity using a vaccine
                          based solely on HIV-1 envelope proteins.
                          Inclusion of conserved core and polymerase
                          proteins along with envelope protein in a
                          candidate vaccine may address some of the
                          problems with antigenic variability. A
                          prime-boost immunization approach using a
                          novel priming immunogen expressing env, gag,
                          and pol genes of the HIV-1 IIIB strain will
                          be attempted in this study.
GENERAL DESCRIPTION       METHODOLOGY: In Part I, vaccinia-immune
                          volunteers are randomized to one of two
                          regimens. Group A receives priming with
                          TBC-3B on days 1 and 56, followed by boosting
                          on day 224 (8 months) with one of the
                          following: TBC-3B, an alternative immunogen
                          such as pseudovirion particles or a
                          recombinant HIV-1 subunit or peptide vaccine,
                          or placebo. Group B receives priming with
                          control vaccine (DryVax), followed by
                          boosting with an appropriate placebo. At
                          least 50 percent of subjects in Part I will
                          be observed for a minimum of 8 weeks before
                          subsequent volunteers are enrolled in Part
                          II. In Part II, vaccinia-naive volunteers are
                          randomized to one of three regimens. Group C
                          receives TBC-3B on day 0 and saline placebo
                          on day 56. Group D receives TBC-3B on days 0
                          and 56. Both Group C and D receive boosting
                          with TBC-3B or an alternative immunogen on
                          day 224. Group E receives control vaccine
                          (DryVax) on days 0 and 56, followed by
                          appropriate placebo on day 224. Per 06/10/94
                          addendum, volunteers will be contacted once
                          or twice per year for at least 5 years to
                          check on health status.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940427)
DISEASE STUDIED           Healthy.
DISEASES STATUS           Subjects have the following conditions: 1.
                          Negative for HIV-1 by ELISA and Western blot
                          within 6 weeks prior to immunization. 2.
                          Normal history and physical exam. 3. History
                          of smallpox vaccination at least 5 years
                          prior to study entry (Part I) OR no prior
                          smallpox vaccination (Part II). 4. Absolute
                          CD4 count >= 400 cells/mm3. 5. Normal
                          urinalysis.
ELIGIBILITY               HIV Seronegative.
OTHER PROTOCOL NUMBERS    IND BB4930
STUDY DESIGN              Multicenter; Randomized; Placebo-Controlled;
                          Double-Blind
PROTOCOL DETAILS          STUDY INTENT: Immunology, Drug safety,
                          Vaccine prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 50 patients. (18 patients
                          in Part I; 32 patients in Part II)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 18 months, with
                          follow-up once or twice yearly for at least 5
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 18/50 (941109).
PROTOCOL DETAILS          STUDY DURATION: 1.5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Subjects must
                          have: 1. Negative ELISA and Western blot for
                          HIV-1 within 6 weeks prior to immunization.
                          2. Normal history and physical exam. 3.
                          History of smallpox vaccination at least 5
                          years prior to study entry (Part I) OR no
                          prior smallpox vaccination (Part II). 4.
                          Absolute CD4 count >= 400 cells/mm3. 5.
                          Normal urinalysis. NOTE: No more than 10
                          percent of volunteers in both Parts I and II
                          may be over 50 years of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 34 percent. (women); >= 38
                          percent (men).
PATIENT INCLUSION CRIT.   PLATELET COUNT: 150000 - 550000
                          platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3. ( 400
                          - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 1.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Total lymphocytes >= 800 cells/mm3.
                          WBC >= 3500 cells/mm3 with normal
                          differential.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Subjects with the
                          following prior conditions are excluded: 1.
                          History of immunodeficiency, chronic illness,
                          autoimmune disease, or use of
                          immunosuppressive medications. 2. History of
                          anaphylaxis or other serious adverse
                          reactions to vaccines. 3. Eczema within the
                          past year. 4. History of serious allergic
                          reaction to any substance, requiring
                          hospitalization or emergent medical care
                          (e.g., Steven-Johnson syndrome, bronchospasm,
                          or hypotension). 5. Prior psychiatric
                          condition (such as history of suicide
                          attempts or past psychosis) that precludes
                          compliance. 6. History of cancer unless there
                          has been surgical excision that is considered
                          to have achieved cure. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: It is STRONGLY RECOMMENDED
                          that any activity that might expose subject
                          to HIV (unprotected sex or needle sharing) be
                          avoided.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Receipt of blood
                          products or immunoglobulins within the past 6
                          months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior HIV
                          vaccines. 2. Live attenuated vaccines within
                          the past 60 days. NOTE: Medically indicated
                          subunit or killed vaccines (e.g., influenza,
                          pneumococcal) do not exclude but should be
                          administered at least 2 weeks prior to HIV
                          immunizations. 3. Experimental agents within
                          the past 30 days.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Subjects with the following
                          symptoms or conditions are excluded: 1.
                          Positive hepatitis B surface antigen. 2.
                          Medical or psychiatric condition (such as
                          recent suicidal ideation or present
                          psychosis) that precludes compliance. 3.
                          Occupational responsibilities that preclude
                          compliance. 4. Active syphilis. NOTE:
                          Subjects with serology documented to be a
                          false positive or due to a remote (> 6
                          months) treated infection are eligible. 5.
                          Active tuberculosis. NOTE: Subjects with a
                          positive PPD and a normal chest x-ray showing
                          no evidence of TB and not requiring isoniazid
                          therapy are eligible. 6. Eczema. 7. Household
                          contact with persons meeting any of the
                          following criteria: pregnancy, less than 12
                          months of age, eczema, immunodeficiency
                          disease, or use of immunosuppressive
                          medications.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unavailable for 18 months of
                          follow-up.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0089  Smallpox vaccine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0206  TBC-3B Vaccine
TRADE NAME OF SUBSTANCE   Drug 1 DryVax
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Therion Biologics Corporation 76
                          Rogers Street Cambridge, MA 02142 Contact: Dr
                          Dennis Panicali (617) 876-7779 Contact: Gail
                          Mazzara (617) 876-7779.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Groups B and E:
                          Administered on days 0 and 56, followedby
                          boost with same control vaccine or placebo on
                          day 224. Drug 2: Groups A and D: Administered
                          on days 0 and 56, with boousing the candidate
                          vaccine, other immunogen, or placebo on
                          dayGroup C: Administered on day 0, with
                          placebo given on day 56, followed by boost
                          using the candidate vaccine, other
                          immunogen,placebo on day 224
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Scarification using
                          bifurcated needle. Drug 2: Scarification
                          using bifurcated needle
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (VEU).
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              HIV Infections/*PREVENTION & CONTROL
MESH HEADING              HIV-1/*IMMUNOLOGY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Smallpox Vaccine
MESH HEADING              Vaccines, Synthetic
MESH HEADING              Vaccinia Virus/*IMMUNOLOGY
MESH HEADING              Viral Vaccines
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
CAS REGISTRY NUMBER       0 (Smallpox Vaccine)
CAS REGISTRY NUMBER       0 (Viral Vaccines)
LAST REVISION DATE        940427
ENTRY MONTH               9404
MARYLAND                  Johns Hopkins University / Center for
                          Immunization Research Hampton House Rm 125 /
                          624 North Broadway Baltimore, MD 21205
                          Contact: Karen Charron (410) 955-7283 OPEN
                          941110 ACTU: 6002.
MISSOURI                  St Louis University School of Medicine / Sec
                          Inf Dis 1402 South Grand Boulevard St Louis,
                          MO 63104 Contact: Dr Robert B Belshe (314)
                          577-8648 Contact: Heidi Israel (314) 577-8649
                          OPEN 940411 ACTU: 6007.
NEW YORK                  University of Rochester Medical Center Box
                          689 / Room 36209 / 601 Elmwood Avenue
                          Rochester, NY 14642 Contact: Dr Michael
                          Keefer (716) 275-0810 OPEN 940328 ACTU: 6005.
 
6
UNIQUE IDENTIFIER         NIH/00512
PROTOCOL ID NUMBERS       NIAID VEU 013B
PROTOCOL TITLE            A Phase I, Multicenter, Clinical Trial to
                          Evaluate the Safety and Immunogenicity of
                          Vaccinia-Derived MN HIV-1 Recombinant
                          Envelope Glycoprotein (rgp160) of Human
                          Immunodeficiency Virus in Combination With
                          Recombinant Vaccinia-HIV-1 LAV Envelope
                          Vaccine (HIVAC-1e): Part B.
VERSION NUMBER & DATE     (930210)
TRIAL CATEGORY            Vaccines
TRIAL CATEGORY            HIV Negative
PROTOCOL CHAIRS           CHAIR  Gorse G
GENERAL DESCRIPTION       PURPOSE: To determine in healthy volunteers
                          the safety and immunogenicity of two
                          immunizations of MN rgp160 vaccine
                          (Immuno-AG) in combination with a live
                          recombinant vaccinia virus LAV HIV-1 gp160
                          vaccine (HIVAC-1e) versus DryVax (the
                          standard smallpox vaccine that was used for
                          many years) control in combination with
                          placebo.
GENERAL DESCRIPTION       RATIONALE: A gp160 vaccine derived from the
                          MN strain, the most prevalent strain of HIV-1
                          in the United States, has been developed. A
                          previous study showed that a combination
                          vaccine strategy, consisting of priming with
                          HIVAC-1e followed by boosting with a gp160
                          subunit vaccine, resulted in humoral and
                          cellular immune responses of greater and
                          longer duration than either vaccine alone.
                          Thus, a live vector/subunit boost approach
                          using the MN rgp160 vaccine merits
                          investigation.
GENERAL DESCRIPTION       METHODOLOGY: Volunteers are randomized to
                          receive either HIVAC-1e on days 0 and 56
                          followed by immunization with MN rgp160
                          vaccine on days 224 and 364, or DryVax
                          control on days 0 and 56 followed by placebo
                          on days 224 and 364. Ten volunteers are
                          entered on the MN rgp160 vaccine arm and two
                          volunteers on the placebo arm.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (940615)
DISEASE STUDIED           Healthy.
DISEASES STATUS           Subjects have the following conditions: 1.
                          Normal history and physical exam. 2. Negative
                          for HIV by ELISA within 6 weeks prior to
                          immunization. 3. Negative for HIV by Western
                          blot (i.e., no reactivity at gp160, gp120,
                          and gp41). Exceptions may be made if patients
                          have a p24 band on Western blot and other
                          tests are negative. 4. CD4 count >= 400
                          cells/mm3. 5. No history of smallpox
                          vaccination. 6. Normal urine dipstick with
                          esterase and nitrate. 7. No history of
                          immunodeficiency, chronic illness, autoimmune
                          disease, or use of immunosuppresssive
                          medications.
ELIGIBILITY               HIV Seronegative.
OTHER PROTOCOL NUMBERS    IND BB4949
STUDY DESIGN              Multicenter; Randomized; Placebo-Controlled
PROTOCOL DETAILS          STUDY INTENT: Vaccine prophylaxis, Drug
                          safety, Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 16 patients.
PROTOCOL DETAILS          STUDY DURATION: 18 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Subjects must
                          have: 1. Normal history and physical exam. 2.
                          Negative test for HIV by ELISA within 6 weeks
                          prior to immunization. 3. Negative test for
                          HIV by Western blot. 4. CD4 count >= 400
                          cells/mm3. 5. No history of smallpox
                          vaccination. 6. Normal urine dipstick with
                          esterase and nitrate. 7. No history of
                          immunodeficiency, chronic illness, autoimmune
                          disease, or use of immunosuppresssive
                          medications. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 34 percent. (women); >= 38
                          percent (men).
PATIENT INCLUSION CRIT.   PLATELET COUNT: 150000 - 550000
                          platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3. ( 400
                          - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 1.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: White blood cell count >= 3500
                          cells/mm3 with normal differential. Total
                          lymphocyte count >= 800 cells/mm3.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Subjects with the
                          following prior conditions are excluded: 1.
                          History of anaphylaxis or other serious
                          adverse reactions to vaccines. 2. Eczema
                          within the past year. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Higher risk behavior for HIV
                          infection as determined by screening
                          questionnaire, including: 1. History of
                          injection drug use within 12 months prior to
                          study entry. 2. Higher or intermediate risk
                          sexual behavior.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Blood products or
                          immunoglobulin within the past 6 months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior HIV
                          vaccines. 2. Live attenuated vaccines within
                          the past 60 days. NOTE: Medically indicated
                          subunit or killed vaccines (e.g., influenza,
                          pneumococcal) do not exclude but should be
                          administered at least 2 weeks prior to HIV
                          immunizations. 3. Experimental agents within
                          the past 30 days.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Subjects with the following
                          conditions are excluded: 1. Positive for
                          hepatitis B surface antigen. 2. Medical or
                          psychiatric condition or occupational
                          responsibilities that preclude compliance. 3.
                          Active syphilis (NOTE: If serology is
                          documented to be a false positive or due to a
                          remote (> 6 months) infection, subject is
                          eligible). 4. Active tuberculosis (NOTE:
                          Subjects with a positive PPD and normal x-ray
                          showing no evidence of TB and who do not
                          require INH therapy are eligible). 5. Eczema.
                          6. Household contact with persons meeting any
                          of the following criteria: pregnancy, < 12
                          months of age, eczema, or immunodeficiency
                          disease or use of immunosuppressive
                          medications.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unavailable for 18 months of
                          follow-up.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0162  gp160 Vaccine (Immuno-AG)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0059  HIVAC-1e
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0089  Smallpox vaccine
TRADE NAME OF SUBSTANCE   Drug 3 DryVax
MANUFACTURERS             Drug 1: Immuno-US Incorporated / Media
                          Information Office c/o Cooney/Waters Group /
                          99 Park Avenue / Suite 25 New York, NY 10016
                          Contact: Sherri Michelstein (212) 557-7111.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Jennifer Jackson (203)
                          284-6172.
MANUFACTURERS             Drug 3: Wyeth-Ayerst Research PO Box 8299
                          Philadelphia, PA 19101 Contact: Dr Gary
                          Horwith (610) 341-5770.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mcg (or placebo)
                          on days 224 and 364. Drug 2: Administered on
                          days 0 and 56. Drug 3: Administered on days 0
                          and 56
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intramuscular
                          injection. Drug 2: Scarification using
                          bifurcated needle. Drug 3: Scarification
                          using bifurcated needle
OTHER TREATMENT INFO.     END POINT: Vaccine safety, immunogenicity.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (VEU).
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              Gene Products, env/*IMMUNOLOGY
MESH HEADING              HIV Infections/*PREVENTION & CONTROL
MESH HEADING              HIV-1/*IMMUNOLOGY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Protein Precursors/*IMMUNOLOGY
MESH HEADING              Smallpox Vaccine
MESH HEADING              Vaccines, Synthetic
MESH HEADING              Vaccinia Virus/*IMMUNOLOGY
MESH HEADING              Viral Vaccines
CAS REGISTRY NUMBER       0 (HIV envelope protein gp160)
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
CAS REGISTRY NUMBER       0 (Smallpox Vaccine)
CAS REGISTRY NUMBER       0 (Viral Vaccines)
LAST REVISION DATE        940615
ENTRY MONTH               9304
MISSOURI                  St Louis University School of Medicine / Sec
                          Inf Dis 1402 South Grand Boulevard St Louis,
                          MO 63104 Contact: Dr Robert B Belshe (314)
                          577-8648 Contact: Heidi Israel (314) 577-8649
                          OPEN 930420 ACTU: 6007.
 
7
UNIQUE IDENTIFIER         NIH/00519
PROTOCOL ID NUMBERS       NIAID DATRI 008
PROTOCOL TITLE            A Pilot Study of Methodology to Rapidly
                          Evaluate Drugs for Bactericidal Activity,
                          Tolerance, and Pharmacokinetics in the
                          Treatment of Pulmonary Tuberculosis Using
                          Isoniazid and Levofloxacin.
VERSION NUMBER & DATE     3 (940819)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the methodology for
                          rapidly determining the early bactericidal
                          activity (EBA), tolerance, and
                          pharmacokinetics of isoniazid and
                          levofloxacin in the treatment of pulmonary
                          tuberculosis (TB).
GENERAL DESCRIPTION       RATIONALE: Traditionally, in trials for
                          treatment of TB, a new drug is administered
                          in combination with two or more other
                          antituberculous agents of known effectiveness
                          over a long period of time. In this setting,
                          it is difficult to determine the effect of
                          any single drug or dose level. Development of
                          new agents for the treatment of TB may be
                          accelerated by a methodology in which a new
                          agent could be evaluated for activity by
                          administering it as a single agent over a
                          short time period. This study utilizes a
                          method to measure the amount of bacteria
                          present each day in the lungs.
GENERAL DESCRIPTION       METHODOLOGY: An initial cohort of patients
                          receive isoniazid (with pyridoxine) daily for
                          5 days. Sputum samples are collected daily
                          for determination of the EBA (decline in
                          colony-forming units/ml sputum). If the
                          methodology is validated, additional patients
                          are randomized to receive one of two doses of
                          levofloxacin daily for 5 days, with
                          determination of EBA. All patients are
                          hospitalized for 2 days of baseline
                          evaluation and 5 days of treatment.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Tuberculosis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Presumptive active pulmonary
                          TB as evidenced by a sputum smear positive
                          for acid-fast bacilli (AFB) AND a chest
                          radiograph and other clinical signs and
                          symptoms compatible with active pulmonary TB.
                          2. Either HIV positive or HIV negative. 3. No
                          clinical evidence of central nervous system
                          or miliary tuberculosis.
ELIGIBILITY               AIDS. HIV Seronegative / OTHER.
OTHER PROTOCOL NUMBERS    IND 42,061
STUDY DESIGN              Pilot Study; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug tolerance,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 44 patients. (At least 24
                          patients in the isoniazid pilot; at least 20
                          patients in the levofloxacin portion of the
                          study).
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 7 days.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 17/44 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 9 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Presumptive active pulmonary TB. 2.
                          No clinical evidence of central nervous
                          system or miliary tuberculosis. NOTE: Both
                          HIV-positive and HIV-negative patients are
                          eligible. NOTE: Pregnant women may be
                          enrolled in the isoniazid cohort only. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl. (men); >= 8.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min.
                          (levofloxacin cohort); >= 40 ml/min
                          (isoniazid cohort).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 5 x ULN.
                          Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   WEIGHT: 40 kg.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed in all
                          patients: Antacids if administered more than
                          2 hours before or after study drug. Allowed
                          in isoniazid patients: Anticonvulsant therapy
                          if blood levels are monitored. Allowed in
                          levofloxacin patients: 1. Acceptable
                          medications other than antacids if
                          administered at least 2 hours before or 1
                          hour after study drug. 2. Anticonvulsant
                          therapy, theophylline, or warfarin if doses
                          are monitored.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of treatment-limiting intolerance or
                          known hypersensitivity to isoniazid (in
                          patients receiving isoniazid) or to
                          quinolones (in patients receiving
                          levofloxacin). 2. Vomiting or diarrhea >=
                          grade 2 at screening or within 2 days prior
                          to screening. 3. History of drug-resistant TB
                          (in patients receiving isoniazid). [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: No abstinence or no
                          agreement to use barrier methods of birth
                          control / contraception during the study.
PATIENT EXCLUSION CRIT.   WEIGHT: < 40 kg.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Known risk factors for
                          multi-drug resistant (MDR) TB, including: o
                          Domicile, shelter, or prison exposure to a
                          known case of MDR TB within the past 6
                          months. o Residence in a specific domicile,
                          shelter, or prison cell block within 6 months
                          of a known outbreak of MDR TB. o
                          Hospitalization, within the past 6 months, on
                          a medical service
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any prior
                          treatment or prophylaxis for TB if enrolling
                          on the isoniazid cohort. 2. Any anti-TB drug
                          within the past 12 weeks, including standard
                          drugs against TB as well as clofazimine,
                          rifabutin, and all quinolones and
                          aminoglycosides. 3. Corticosteroids,
                          pentoxifylline, colony-stimulating factors,
                          interferons, or interleukins within the past
                          12 weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. All
                          standard TB therapies. 2. Clofazimine. 3.
                          Rifabutin. 4. Quinolones. 5. Aminoglycosides.
                          6. Corticosteroids. 7. Pentoxifylline. 8.
                          Colony-stimulating factors. 9. Interferons.
                          10. Interleukins. 11. Disulfiram (patients
                          receiving isoniazid).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active or suspected MAI infection. 2. Active
                          or suspected hepatitis. 3. Any other serious
                          acute infection, diabetes, chronic
                          obstructive pulmonary disease, malignancy
                          requiring chemotherapy, or major organ
                          dysfunction. 4. Extreme illness or toxic
                          appearance. 5. Pregnancy (if entering the
                          levofloxacin portion of the study).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0123  Isoniazid
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0125  Pyridoxine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0129  Levofloxacin
MANUFACTURERS             Drug 1: Barr Laboratories Incorporated 2
                          Quaker Road PO Box D-2900 Pomona, NY 10970
                          Contact: Unspecified (914) 362-1100.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Ortho Pharmaceutical Corporation
                          Route 202 / PO Box 300 Raritan, NJ 08869-0602
                          Contact: Dr Vincent Ahonkha (908) 704-4991.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 300 mg daily for 5
                          days. Drug 2: 50 mg daily for 5 days (with
                          isoniazid). Drug 3: 500 or 750 mg daily for 5
                          days
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 300 mg. Drug 2: 50 mg.
                          Drug 3: 500 or 750 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 300 mg tablets.
                          Drug 2: Oral, 50 mg tablets. Drug 3: Oral,
                          125 and 500 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 5 days.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Significant
                          toxicity. 2. Significant clinical
                          deterioration or disease progression. 3.
                          Further participation deemed detrimental to
                          patient's health or well-being. 4. Production
                          of sputum inadequate to complete laboratory
                          evaluations. 5. Inability to continue study
                          drug. 6. Indication for systemic cytotoxic
                          therapy for a newly diagnosed malignancy. 7.
                          Major protocol violation. 8. At the request
                          of the patient.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (DATRI).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Colony Count, Microbial
MESH HEADING              Drug Evaluation
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Isoniazid/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Ofloxacin/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/PHARMACOKINETICS/*THERAPEUTIC USE
MESH HEADING              Opportunistic Infections/COMPLICATIONS/*DRUG
                          THERAPY/MICROBIOLOGY
MESH HEADING              Pyridoxine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Sputum/*MICROBIOLOGY
MESH HEADING              Tuberculosis, Pulmonary/COMPLICATIONS/*DRUG
                          THERAPY/MICROBIOLOGY
CAS REGISTRY NUMBER       54-85-3 (Isoniazid)
CAS REGISTRY NUMBER       65-23-6 (Pyridoxine)
CAS REGISTRY NUMBER       82419-36-1 (Ofloxacin)
LAST REVISION DATE        941207
ENTRY MONTH               9308
ALABAMA                   University of Alabama at Birmingham 619 South
                          19th Street Birmingham, AL 35233-6505
                          Contact: Penny Phillips (205) 975-5748
                          Contact: FAX (205) 934-1721 OPEN 931222.
CALIFORNIA                UCLA School of Medicine 10833 LeConte Ave Los
                          Angeles, CA 90024-1793 Contact: Dr David
                          Hardy (310) 206-5427 OPEN 940218.
CALIFORNIA                Harbor UCLA Medical Center 1124 West Carson /
                          N-24 Torrance, CA 90502 Contact: Sally Kruger
                          (310) 222-3848 OPEN 931006.
FLORIDA                   University of Miami / Jackson Memorial
                          Hospital 1611 NW 12th Avenue Miami, FL 33101
                          Contact: Portia James (305) 585-7223 OPEN
                          940615.
FLORIDA                   Broward General Medical Center 1600 South
                          Andrews Avenue Ft. Lauderdale, FL 33316
                          Contact: Tim Palmer-Pattison (305) 467-3006
                          Contact: (305) 355-5560 OPEN 930818.
ILLINOIS                  University of Illinois 833 S Wood Street M/C
                          886 Chicago, IL 60622 Contact: Dr Jenny
                          Colombo (312) 996-2133 OPEN 940629.
LOUISIANA                 Tulane U School of Medicine \ General
                          Clinical Research Ctr 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Dana Wineski
                          (504) 585-4020 OPEN 930818.
 
8
UNIQUE IDENTIFIER         NIH/00501
PROTOCOL ID NUMBERS       NIAID DATRI 007
PROTOCOL TITLE            The Effect of Therapy on the Tissue Burden of
                          Disseminated MAC Infection as Measured by
                          Quantitative Bone Marrow Culture and
                          Correlation With Quantitative Blood Culture
                          in HIV-Infected Patients.
VERSION NUMBER & DATE     4 (940119)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To assess the feasibility of using
                          culture and staining techniques to quantify
                          tissue Mycobacterium avium Complex (MAC)
                          burden in bone marrow. To correlate and
                          compare changes in MAC bone marrow burden
                          with quantitative MAC blood culture results
                          at baseline and after 4 and 8 weeks of
                          treatment.
GENERAL DESCRIPTION       RATIONALE: MAC is easiest to detect in the
                          blood, although doctors generally believe
                          that MAC in blood is just spill-over from
                          infection of other parts of the body.
                          Traditionally, studies of potential
                          treatments for MAC focus only on MAC changes
                          in the blood. This study compares MAC changes
                          in blood to those in bone marrow, which is
                          another tissue where MAC is often found.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive both
                          clarithromycin and ethambutol for 48 weeks;
                          those who become intolerant to the study
                          drugs may receive suggested substitute drugs
                          (azithromycin and rifabutin). Patients
                          receive a bone marrow biopsy at baseline and
                          at either 4 or 8 weeks. Patients are
                          evaluated at weeks 1, 2, 4, 6, 8, 12, 24, 36,
                          and 48.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by a
                          clinical history compatible with HIV disease
                          or by ELISA confirmed by Western blot,
                          positive HIV culture, positive HIV antigen,
                          plasma viremia, or a second antibody test
                          positive by a method other than ELISA. 2.
                          Confirmed MAC bacteremia.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 41,772
STUDY DESIGN              Open Label; Randomized; Pilot Study; Drug
                          Combination
PROTOCOL DETAILS          STUDY INTENT: Combination pharmacokinetics,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 14/24 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Confirmed MAC
                          bacteremia. 3. Consent of parent or guardian
                          if less than 18 years of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 3.0 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Any
                          antiretroviral therapy that is approved or is
                          available through an FDA-sanctioned treatment
                          IND or treatment protocol. 2. Primary or
                          secondary PCP prophylaxis with TMP/SMX,
                          dapsone, or aerosolized pentamidine, as well
                          as approved therapies for other AIDS-related
                          opportunistic infections not otherwise
                          excluded. 3. Erythromycin, interferon-alpha,
                          and supportive care for any therapy-related
                          toxicities as necessary.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of treatment-limiting intolerance or
                          hypersensitivity to the study drugs or other
                          macrolides. 2. Changes on chest radiograph
                          within 7 days prior to study entry, that are
                          consistent with acute Pneumocystis carinii
                          pneumonia, pulmonary tuberculosis, or other
                          acute respiratory infection. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Clarithromycin, azithromycin, or ethambutol
                          for more than 10 consecutive days within the
                          8 weeks prior to study entry OR between the
                          time an initial AFB positive blood sample was
                          collected and study entry. 2. Cytokines
                          (other than erythropoietin and
                          interferon-alpha) within 8 weeks prior to
                          study entry. 3. Steroids within 8 weeks prior
                          to study entry. 4. Cytotoxic chemotherapy
                          within 8 weeks prior to study entry. 5. Acute
                          therapy for an AIDS-related opportunistic
                          infection or malignancy, or other acute
                          medical illness or infection within 4 weeks
                          prior to study entry. 6. Rifabutin
                          monotherapy if initiated for MAC prophylaxis
                          between the time an initial AFB positive
                          blood sample was collected and study entry.
                          7. Aminoglycosides, quinolones, clofazimine,
                          or rifamycins IF ADMINISTERED IN ANY
                          COMBINATION within 7 days prior to study
                          entry OR between the time an initial AFB
                          positive blood sample was collected and study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. MAC
                          inhibitors, including aminoglycosides,
                          quinolones, clofazimine, azithromycin (except
                          when administered as a substitute drug), and
                          rifamycins, during the first 24 weeks of the
                          study. 2. Immunomodulators (including
                          colony-stimulating cytokines such as GM-CSF
                          and G-CSF) other than those that are
                          specifically allowed. 3. Steroids in excess
                          of physiologic replacement doses. 4.
                          Cytotoxic chemotherapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0099  Clarithromycin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0111  Ethambutol
TRADE NAME OF SUBSTANCE   Drug 1 Biaxin
TRADE NAME OF SUBSTANCE   Drug 2 Myambutol
MANUFACTURERS             Drug 1: Abbott Laboratories One Abbott Park
                          Road Abbott Park, IL 60064 Contact: Dr J Carl
                          Craft (708) 937-8147.
MANUFACTURERS             Drug 2: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 500 mg BID for 48
                          weeks. Drug 2: 15 mg/kg (to a maximum of 1200
                          mg) daily for 48 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1000 mg. Drug 2: 15
                          mg/kg (to a maximum of 1200 mg)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 500 mg tablets.
                          Drug 2: Oral, 100 and 400 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Quantitative changes in blood and
                          bone marrow MAC load after 4 and 8 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Development of
                          an AIDS-related opportunistic infection or
                          malignancy, or other medical condition
                          requiring the use of non-permitted or
                          contraindicated medications. 2. Drug-related,
                          dose-limiting toxicity. 3.
                          Physician-documented clinical failure after 8
                          weeks of study therapy. 4.
                          Physician-documented significant clinical
                          deterioration at any time. 5. Failure to
                          achieve at least a one log decrease in total
                          colony-forming units (CFU) of MAC from a
                          blood sample at week 8 of study. 6. Desire of
                          patient to withdraw from study.
OTHER TREATMENT INFO.     MODIFICATION: For reduced color
                          differentiation or significant loss of visual
                          acuity: Discontinue ethambutol permanently
                          unless another cause has been identified. For
                          severe or life threatening nausea, vomiting,
                          diarrhea, or other adverse reactions or for
                          bilirubin > 2.5 x ULN or LFTs > 5 x ULN: Hold
                          study drugs for up to 3 days until symptoms
                          resolve, then restart study therapies (at
                          initial doses) in a step-wise manner,
                          allowing 48-72 hours between the start of
                          each drug.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (DATRI).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Clarithromycin/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       81103-11-9 (Clarithromycin)
LAST REVISION DATE        941207
ENTRY MONTH               9307
ARIZONA                   University of Arizona / Section of Infectious
                          Diseases 1501 North Campbell Avenue Tucson,
                          AZ 85724 Contact: Joel Gray (602) 626-2533
                          OPEN 930804.
MARYLAND                  University of Maryland 22 South Greene Street
                          P O Box 243 Baltimore, MD 21201 Contact:
                          Troylynn Maupin (410) 328-3588 OPEN 931222.
NEW JERSEY                University of Med and Dentistry of New Jersey
                          / Cooper 401 Haddon Avenue / Dept of Medicine
                          Room 277 Camden, NJ 08103 Contact: Barbara
                          McCall (609) 963-3833 OPEN 930630.
NEW YORK                  SUNY at Stony Brook Health Sciences Center /
                          Div Infect Dis HSC T 15 Room 080 Stony Brook,
                          NY 11794-8153 Contact: Ruth Ann Burk (516)
                          444-1658 OPEN 930901.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 931006 ACTU: 7401.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn / Suite 770 Portland, OR 97210
                          Contact: Sue Peterson (503) 795-6639 Contact:
                          FAX (503) 274-4892 OPEN 930630.
 
9
UNIQUE IDENTIFIER         NIH/00453
PROTOCOL ID NUMBERS       NIAID DATRI 002
PROTOCOL TITLE            Pilot Study to Evaluate the Efficacy of
                          Zidovudine in Preventing CD4+ Lymphocyte
                          Decline in Patients With Primary HIV
                          Infection. (One treatment arm receives
                          placebo.)
VERSION NUMBER & DATE     4 (940803)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and efficacy
                          of early treatment with zidovudine for
                          preventing a decline in CD4+ lymphocyte
                          counts in patients with primary HIV
                          infection. To determine the natural history
                          of virologic and immunologic changes in
                          primary HIV infection.
GENERAL DESCRIPTION       RATIONALE: Previous studies indicate that
                          intervention with zidovudine during primary
                          HIV infection could reduce the initial viral
                          burden and subsequent decline in immune
                          functions, and could prolong not only the
                          time to development of AIDS but also the time
                          to initiation of chronic antiretroviral
                          therapy.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either zidovudine (1000 mg) or
                          placebo daily for 24 weeks. Patients are
                          followed until development of an AIDS-related
                          opportunistic infection or malignancy. After
                          week 24, patients meeting standard
                          prescribing criteria may start FDA-approved
                          anti-HIV therapies. After study week 48,
                          patients may co-enroll on another clinical
                          trial to receive experimental therapy.
PROTOCOL PHASE            Phase I / Pilot Study
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: Asymptomatic or symptomatic
                          primary HIV infection, plus one of the
                          following two criteria- 1) p24 antigenemia
                          documented within 1 month prior to study
                          entry and either HIV enzyme immunoassay (IA)
                          negative or HIV IA positive with Western blot
                          negative/indeterminate, within 1 month prior
                          to study entry. 2) Documented seroconversion
                          within 1 month prior to study entry and
                          Western blot negative/indeterminate.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    IND 28,972
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Pilot Study; 2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 80 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Patients
                          receive treatment on study for 24 weeks.
                          Following treatment, patients continue to be
                          followed until development of an AIDS-related
                          opportunistic infection or malignancy.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 17/80 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 9 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic or symptomatic primary
                          HIV infection, plus one of the following two
                          criteria- a) p24 antigenemia documented
                          within 1 month prior to study entry and
                          either HIV enzyme immunoassay (IA) negative
                          or HIV IA positive with Western blot
                          negative/indeterminate, within 1 month prior
                          to study entry. b) Documented seroconversion
                          within 1 month prior to study entry and
                          Western blot negative/indeterminate. 2.
                          Consent of parent or guardian if less than 18
                          years of age. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl. (men); >= 8.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          during the study and for 90 days after.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Medications
                          for nausea, vomiting, analgesia, or anxiety.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 90 days after.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Chronic
                          steroid use. 2. Immunomodulators. 3.
                          Myelosuppressive agents. 4. Other
                          antiretroviral agents or experimental
                          therapies (NOTE: FDA-approved therapies
                          permitted in patients who qualify after week
                          24; experimental therapies permitted after
                          study week 48).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          condition are excluded: poor venous access.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or placebo)
                          5x daily for 24 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1000 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Acute medical
                          conditions that necessitate use of excluded
                          medications. 2. Unacceptable toxicity.
OTHER TREATMENT INFO.     MODIFICATION: Dose reductions, with or
                          without dose interruption, are permitted.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (DATRI), Burroughs Wellcome.
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY/IMMUNOLOGY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        941207
ENTRY MONTH               9301
CALIFORNIA                Cedars-Sinai Medical Center 8700 Beverly
                          Boulevard / Becker 226 Los Angeles, CA 90048
                          Contact: Cyndi Frank (310) 855-3755 Contact:
                          Eric Daar (310) 855-3896 OPEN 930203.
CALIFORNIA                Veterans Administration Medical Center Palo
                          Alto 3801 Miranda Ave / Suite 119 Palo Alto,
                          CA 94304 Contact: Larry Mole (415) 493-5000 X
                          469OPEN 921230.
FLORIDA                   Broward General Medical Center 1600 South
                          Andrews Avenue Ft. Lauderdale, FL 33316
                          Contact: Tim Palmer-Pattison (305) 467-3006
                          Contact: (305) 355-5560 OPEN 930428.
ILLINOIS                  University of Illinois / Section of
                          Infectious Diseases 840 South Wood Street /
                          Room 908 Chicago, IL 60612 Contact: Dr Luis
                          Moriera (312) 996-7870 Contact: Beeper (312)
                          996-7000 X 730OPEN 930901.
MARYLAND                  Johns Hopkins University School of Medicine
                          600 North Wolfe Street / Marburg B-186
                          Baltimore, MD 21287-2080 Contact: Judy Shahan
                          (410) 955-8708 OPEN 930721.
NEW YORK                  Bellevue Hospital / NYU 462 East 27th Street
                          New York, NY 10016 Contact: Richard Hutt
                          (212) 561-3906 OPEN 930818.
RHODE ISLAND              Miriam Hospital / Brown University 164 Summit
                          Avenue Providence, RI 02906 Contact: Dr
                          Josiah Rich (401) 331-8500 X 715OPEN 930127.
 
10
UNIQUE IDENTIFIER         NIH/00470
PROTOCOL ID NUMBERS       NIAID CPCRA 022
PROTOCOL TITLE            The Efficacy of a Standardized Acupuncture
                          Regimen and Amitriptyline Compared With
                          Placebo as a Treatment for Pain Caused by
                          Peripheral Neuropathy in HIV-Infected
                          Patients.
VERSION NUMBER & DATE     4 (941027)
TRIAL CATEGORY            Neurologic Manifestations
PROTOCOL CHAIRS           CHAIR  Shlay J
PROTOCOL CHAIRS           CO-CHAIR  Flaws B
GENERAL DESCRIPTION       PURPOSE: To evaluate the separate and
                          combined efficacy of a standardized
                          acupuncture regimen and amitriptyline on the
                          relief of pain due to peripheral neuropathy
                          and on the quality of life of HIV-infected
                          patients.
GENERAL DESCRIPTION       RATIONALE: Both amitriptyline, an
                          antidepressant, and acupuncture, a Chinese
                          medical approach that uses needles to relieve
                          pain, have been used successfully to reduce
                          pain in some people. It is not known how
                          effectively these approaches relieve or
                          reduce pain in patients with peripheral
                          neuropathy secondary to HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either standardized point acupuncture
                          or alternate point acupuncture treatment
                          twice weekly for the first 6 weeks, then once
                          weekly for the next 8 weeks, plus either oral
                          amitriptyline or placebo daily for the entire
                          14 weeks. Acupuncture points are located on
                          the lower leg. Patients are evaluated at
                          weeks 6 and 14 and are asked to keep a daily
                          pain diary.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Peripheral neuropathy.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Working diagnosis of HIV
                          infection, based on medical history, clinical
                          signs and symptoms, or results of laboratory
                          tests. 2. Lower extremity peripheral
                          neuropathy secondary to HIV infection. 3.
                          Pain for at least 2 weeks prior to study
                          entry.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 41,279
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Multicenter; 4-Arm
PROTOCOL DETAILS          STUDY INTENT: Combination modality therapy,
                          Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 260 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 16 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 80/260 (941207).
PROTOCOL DETAILS          STUDY DURATION: 3.5 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Lower extremity
                          peripheral neuropathy secondary to HIV
                          infection. 3. Pain for at least 2 weeks prior
                          to study entry. 4. Life expectancy of at
                          least 6 months. NOTE: Co-enrollment in other
                          experimental protocols is permitted as long
                          as dual participation is allowed in those
                          protocols. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Required: Acupuncture.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Antiretroviral
                          therapy.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral therapy. 2. Nonsystemic
                          treatment of Kaposi's sarcoma. 3. Maintenance
                          with an existing regimen of analgesic
                          medication or herbal treatment.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded (not
                          applicable for patients at sites using an
                          acupuncture only study design): 1. History of
                          cardiac disease. 2. History of seizure
                          disorder. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 weeks
                          prior to study entry: 1. MAO inhibitors. 2.
                          Tricyclic antidepressants.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Active
                          treatment for an acute opportunistic
                          infection or malignancy (nonsystemic
                          treatment of Kaposi's sarcoma is permitted).
                          2. Other tricyclic antidepressants. 3. MAO
                          inhibitors.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          allergy to amitriptyline (not applicable for
                          patients at sites using an acupuncture only
                          study design). 2. EKG indicating malignant
                          arrhythmia or cardiac conduction disturbances
                          (not applicable for patients at sites using
                          an acupuncture only study design). 3. Prison
                          incarceration.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0169  Amitriptyline hydrochloride
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 25 mg (or placebo)
                          daily as initial dose, with escalatiq 2-3
                          days until 75 mg daily is reached, continuing
                          for 14 weekthen tapering to discontinuation
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 25 mg initial dose,
                          with escalation q 2-3 days up to 75mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 25 mg capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 14 weeks.
OTHER TREATMENT INFO.     END POINT: Primary: Change in pain intensity
                          after 6 and 14 weeks of treatment. Secondary:
                          Change in quality of life and neurological
                          status during treatment, change in pain
                          intensity during a 4-week follow-up period,
                          treatment failure.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Acute illness
                          (e.g., opportunistic infection requiring
                          treatment). 2. Extreme pain that necessitates
                          discontinuation.
OTHER TREATMENT INFO.     MODIFICATION: Patients unable to tolerate 75
                          mg/day amitriptyline may have dose reduced to
                          50 or 25 mg/day or, if necessary, to 25 mg
                          every 2-3 days. For adverse effects caused by
                          acupuncture: Hold acupuncture until the
                          primary physician permits resumption.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (CPCRA).
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Acupuncture Therapy
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Amitriptyline/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pain/*THERAPY
MESH HEADING              Peripheral Nervous System Diseases/
                          *COMPLICATIONS
CAS REGISTRY NUMBER       50-48-6 (Amitriptyline)
LAST REVISION DATE        941207
ENTRY MONTH               9304
CALIFORNIA                Community Consortium of San Francisco 3180
                          18th Street Suite 201 San Francisco, CA 94110
                          Contact: Thomas Mitchell (415) 476-9554 OPEN
                          930427.
COLORADO                  Denver / CPCRA 605 Bannock Street Denver, CO
                          80204-4507 Contact: Jack Rouff (303) 436-7184
                          Contact: (303) 436-7224 OPEN 930427.
NEW YORK                  Harlem AIDS Treatment Group Harlem Hospital /
                          Women's Pavilion Room 126 New York, NY 10037
                          Contact: Joshua Standig (212) 939-2951 OPEN
                          930420.
NEW YORK                  Clinical Directors Network of Region II 5601
                          2nd Avenue #3 Brooklyn, NY 11220 Contact:
                          Linda Podhurst (212) 255-3841 OPEN 930511.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn / Suite 770 Portland, OR 97210
                          Contact: Joyce St Arnaud (503) 229-8428 OPEN
                          930427.
 
11
UNIQUE IDENTIFIER         NIH/00441
PROTOCOL ID NUMBERS       NIAID CPCRA 006
PROTOCOL TITLE            A Randomized, Comparative, Prospective Study
                          of Daily Trimethoprim / Sulfamethoxazole
                          (TMS) and Thrice Weekly TMS for Prophylaxis
                          Against PCP in HIV-Infected Patients.
VERSION NUMBER & DATE     3 (940701)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  El-Sadr W
PROTOCOL CHAIRS           CO-CHAIR  Luskin-Hawk R
GENERAL DESCRIPTION       PURPOSE: To compare the safety and efficacy
                          of two dosage regimens (daily and thrice
                          weekly) of trimethoprim / sulfamethoxazole
                          (TMP/SMX; TMS) in the prevention of
                          Pneumocystis carinii pneumonia (PCP) in
                          high-risk HIV-infected patients.
GENERAL DESCRIPTION       RATIONALE: Previous tests have shown that TMP
                          / SMX given daily is effective in preventing
                          recurrence of PCP and may be effective in
                          preventing PCP in patients who have never
                          developed it. Because TMP / SMX can cause
                          side effects, this study will attempt to
                          determine the safest and most effective dose
                          of this combination.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive TMP / SMX
                          orally on a daily or thrice weekly basis.
                          Patients are clinically evaluated every 4
                          months. Patients on daily TMP / SMX who
                          develop a drug-related toxicity may be
                          switched to thrice-weekly TMP / SMX. Duration
                          of follow-up is 12 months.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Working diagnosis of HIV
                          infection based on patient's medical history,
                          behavioral history, clinical signs and
                          symptoms, and results of laboratory tests. 2.
                          CD4 count <= 200 cells/mm3 or <= 15 percent
                          of total lymphocyte count OR a history of
                          prior PCP. 3. No active pneumocystosis.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Multicenter; Prospective; Randomized;
                          Comparative; 2-Arm; Open Label
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug safety,
                          Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 2500 patients. (1250 on
                          each of two treatment arms)
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1897/2500 (941207).
PROTOCOL DETAILS          STUDY DURATION: Approximately 37 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 19 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count <= 200
                          cells/mm3 OR a history of prior PCP. 3. No
                          active pneumocystosis. Patients or their
                          guardians must sign informed consent.
                          Pregnant patients are eligible at the
                          clinician's discretion. Patients who do not
                          meet required laboratory values may be
                          eligible at the discretion of the clinician.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          Patients with no prior episodes of
                          Pneumocystis carinii pneumonia must have a
                          CD4 count <= 200 cells/mm3 ( 0 - 100 - 200 )
                          or <= 15 percent of total lymphocyte count.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Other PCP
                          prophylaxis or medication with anti-PCP
                          activity.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: Known
                          treatment-limiting reaction to sulfonamides
                          or trimethoprim.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0031  Sulfamethoxazole
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0030  Trimethoprim
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Arm I: 1 DS tablet
                          daily. Arm II: 1 DS tablet 3 times weekly
                          (MWF). Drug 2: Arm I: 1 (double strength) DS
                          tablet daily. Arm II: 1 Dtablet 3 times
                          weekly (MWF)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     END POINT: Primary: Occurrence/recurrence of
                          morphologically or histologically confirmed
                          or probable PCP. Secondary: Development of
                          confirmed or probable toxoplasmosis,
                          development of confirmed or probable
                          extrapulmonary pneumocystosis, drug
                          intolerance/toxicity, and death.
OTHER TREATMENT INFO.     DISCONTINUE: Treatment is temporarily
                          discontinued for the following reasons: 1.
                          Toxicity. 2. Pregnancy. 3. Acute
                          opportunistic or bacterial infection. 4.
                          Opportunistic malignancy. Treatment is
                          permanently discontinued for the following
                          reasons: 1. Severe toxicity that precludes
                          further treatment. 2. Development of illness
                          requiring > 4 weeks of medication with
                          potential anti-PCP activity or that may
                          interact with study drug. 3. Continuation of
                          therapy not considered in the best interest
                          of patient. 4. Refusal of patient to continue
                          study therapy.
OTHER TREATMENT INFO.     MODIFICATION: Patients on daily TMP / SMX may
                          be temporarily or permanently reduced to
                          thrice weekly TMP / SMX if toxicity occurs.
                          If toxicity necessitates interruption of
                          study therapy for more than 4 weeks, the
                          clinician will determine whether study drug
                          may be resumed or permanently discontinued.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (CPCRA), Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *PREVENTION & CONTROL
MESH HEADING              Trimethoprim-Sulfamethoxazole Combination/
                          ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       8064-90-2 (Trimethoprim-Sulfamethoxazole
                          Combination)
LAST REVISION DATE        941207
ENTRY MONTH               9210
CALIFORNIA                Community Consortium of San Francisco 3180
                          18th Street Suite 201 San Francisco, CA 94110
                          Contact: Thomas Mitchell (415) 476-9554 OPEN
                          920924.
COLORADO                  Denver / CPCRA 605 Bannock Street Denver, CO
                          80204-4507 Contact: Jack Rouff (303) 436-7184
                          Contact: (303) 436-7224 OPEN 920731.
DISTRICT OF COLUMBIA      Washington Regional AIDS Program 50 Irving St
                          N W / Room ID-151B Washington, DC 20422
                          Contact: John Scott (202) 745-8695 OPEN
                          921001.
DELEWARE                  Delaware / CPCRA 501 West 14th Street
                          Wilmington, DE 19899 Contact: Arlene Bincsik
                          (302) 428-2538 OPEN 930112.
GEORGIA                   Atlanta AIDS Research Consortium Incorporated
                          131 Ponce deLeon Suite 220 Atlanta, GA 30308
                          Contact: Amy Morris (404) 876-2317 OPEN
                          930127.
ILLINOIS                  Chicago CPCRA 711 West North Avenue Suite 201
                          Chicago, IL 60610 Contact: Jeffrey Zurlinden
                          (312) 266-0227 OPEN 930203.
LOUISIANA                 Louisiana Community AIDS Research Program
                          1430 Tulane Avenue New Orleans, LA 70112
                          Contact: Ermelle Martinez Laurent (504)
                          584-1971 OPEN 921021.
MICHIGAN                  Comprehensive AIDS Alliance of Detroit 4160
                          John R / Harper Hospital Prof Bldg / Suite
                          202 Detroit, MI 48201 Contact: Constance
                          Rowley (313) 993-0934 OPEN 920723.
MICHIGAN                  Henry Ford Hospital 2799 West Grand Boulevard
                          Detroit, MI 48202 Contact: Diane Mastro-Polak
                          (313) 876-7664 OPEN 920910.
NEW JERSEY                North Jersey Community Research Initiative
                          657 King Boulevard Newark, NJ 07102 Contact:
                          Victoria Taylor (201) 648-0350 OPEN 921029.
NEW YORK                  Harlem AIDS Treatment Group Harlem Hospital /
                          Women's Pavilion Room 126 New York, NY 10037
                          Contact: Joshua Standig (212) 939-2951 OPEN
                          920709.
NEW YORK                  Bronx-Lebanon Hospital Center 1309 Fulton
                          Avenue Bronx, NY 10456 Contact: Cathy Pollard
                          (718) 293-2593 Contact: (718) 901-8916 OPEN
                          920918.
NEW YORK                  Addiction Research And Treatment Corporation
                          22 Chapel Street Brooklyn, NY 11201 Contact:
                          Dr Robert Sawyer (718) 260-2917 OPEN 920924.
NEW YORK                  Addiction Research and Treatment Corporation
                          22 Chapel Street Brooklyn, NY 11201 Contact:
                          Robert C Sawyer (718) 260-2917 OPEN 920924.
NEW YORK                  Clinical Directors Network of Region II 5601
                          2nd Avenue #3 Brooklyn, NY 11220 Contact:
                          Linda Podhurst (212) 255-3841 OPEN 921009.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn / Suite 770 Portland, OR 97210
                          Contact: Joyce St Arnaud (503) 229-8428 OPEN
                          940908.
OREGON                    The Research and Education Group 2701
                          Northwest Vaughn / Suite 770 Portland, OR
                          97210-9951 Contact: Robert Forrest, Admin
                          Director (503) 229-8428 Contact: Fax (503)
                          227-0902 OPEN 941123.
 
12
UNIQUE IDENTIFIER         NIH/00235
PROTOCOL ID NUMBERS       NIAID CPCRA 004
PROTOCOL TITLE            Prophylaxis Against Tuberculosis (TB) in
                          Patients With Human Immunodeficiency Virus
                          (HIV) Infection and Confirmed Latent
                          Tuberculous Infection.
VERSION NUMBER & DATE     4 (940630)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Gordin F
PROTOCOL CHAIRS           CO-CHAIR  Brown LS
GENERAL DESCRIPTION       PURPOSE: To evaluate and compare the
                          effectiveness of a 2-month regimen of
                          rifampin and pyrazinamide versus a 1-year
                          course of isoniazid (INH) to prevent the
                          development of tuberculosis in patients who
                          are coinfected with HIV and latent
                          Mycobacterium tuberculosis (MTb).
GENERAL DESCRIPTION       RATIONALE: Current guidelines recommend 6 to
                          12 months of treatment with INH for purified
                          protein derivative (PPD)-positive
                          individuals. Problems with this treatment
                          include compliance, adverse reaction, and the
                          possibility of not preventing disease due to
                          INH-resistant organisms. Studies suggest that
                          two or three months of rifampin and
                          pyrazinamide may be more effective than
                          longer courses of INH. A two month prevention
                          course should help to increase compliance. In
                          addition, the use of two drugs (rifampin and
                          pyrazinamide) may help overcome problems with
                          drug resistance.
GENERAL DESCRIPTION       METHODOLOGY: After baseline screening,
                          patients are randomized to one of two
                          treatment arms and are evaluated by means of
                          clinic visits monthly for the first three
                          months, then every three months for the first
                          year (there are additional clinic visits for
                          INH patients). Patients are then evaluated
                          every six months. One group of patients takes
                          INH, 300 mg/day, and vitamin B6, 50 mg/day,
                          for 12 months. The other group of patients
                          takes rifampin 450 or 600 mg/day (dose
                          depends on patients' weight) plus
                          pyrazinamide 20 mg/kg/day (maximum 3,000
                          mg/day) in 3-4 divided doses for 60 days.
PROTOCOL PHASE            Unspecified
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Tuberculosis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection evidenced by
                          documented positive serology for HIV, OR
                          documented history of any opportunistic
                          infection or malignancy indicative of AIDS by
                          CDC definition, OR a working diagnosis of HIV
                          infection based on the patient's medical
                          history, behavioral history, clinical signs
                          and symptoms, and results of other laboratory
                          tests. 2. Positive PPD (purified protein
                          derivative) skin test WITHOUT evidence of
                          active clinical tuberculosis. (A positive PPD
                          skin test is defined as >= 5 mm induration to
                          5 TU of PPD using the Mantoux method; the
                          optimal time for reading the reaction is
                          between 48 and 72 hours after application,
                          although a positive reaction read beyond 72
                          hours is allowed.) OR Documented history of a
                          positive PPD skin test without subsequent
                          treatment or prophylaxis for more than one
                          month with any antituberculous medication.
ELIGIBILITY               AIDS. ASYM. ARC.
OTHER PROTOCOL NUMBERS    TB/PPD+. IND 37,315
STUDY DESIGN              Prospective; Multicenter; Randomized; Open
                          Label; 2-Arm; Comparative
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination drug therapy, Drug prophylaxis,
                          Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 2000 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 - 6 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1089/2000 (941207).
PROTOCOL DETAILS          STUDY DURATION: Possibly 6 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 24 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Signed informed
                          consent. 3. Reasonably good health at time of
                          study entry. 4. Perceived life expectancy of
                          at least six months. Allowed: Participation
                          in other clinical trials as long as there is
                          no potential activity of other study drugs
                          against Mycobacterium tuberculosis (MTb),
                          additive toxicities between study agents, or
                          known possible drug interactions between
                          study drugs. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. ULN = upper limit of
                          normal.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophil count > 750
                          cells/mm3. Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study. Not pregnant. Negative
                          pregnancy test within 30 days of study entry.
OTHER PATIENT INCL. CH.   RISK BEHAVIOR: Willing and able, in the
                          clinician's opinion, to comply with the
                          treatment and clinical management issues.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Treatment with
                          quinolones, fluoroquinolones,
                          aminoglycosides, or other agents with known
                          or potential activity against M.
                          tuberculosis.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Antiretroviral treatment. Pneumocystis
                          carinii pneumonia prophylaxis. Treatment for
                          acute opportunistic infection/malignancy.
                          Aminoglycosides, quinolones or
                          fluoroquinolones such as ciprofloxacin or
                          ofloxacin for < 14 days for treatment of
                          intercurrent infection.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients may not
                          have: 1. Current active tuberculosis. 2.
                          Acute hepatitis. 3. Peripheral neuropathy of
                          grade 3 or grade 4. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: No abstinence or no
                          agreement to use effective method of birth
                          control / contraception during the study.
                          Pregnant. Positive pregnancy test within 30
                          days of study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: History of
                          treatment for > 2 months with agents that
                          have known or potential antituberculous
                          activity other than those specifically
                          allowed. Agents with potential or known
                          antituberculous activity include the
                          following: 1. Aminoglycosides such as
                          amikacin 2. Aminosalicylic acid salts 3.
                          Capreomycin 4. Ciprofloxacin 5. Clofazimine
                          6. Cycloserine 7. Ethambutol 8. Ethionamide
                          9. Isoniazid 10. Kanamycin 11. Ofloxacin 12.
                          Pyrazinamide 13. Quinolones or
                          fluoroquinolones 14. Rifabutin 15. Rifampin
                          16. Streptomycin 17. Thiacetazone.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Quinolones,
                          fluoroquinolones, or aminoglycosides with
                          antituberulous activity (may be used for up
                          to 14 days for treatment of intercurrent
                          infection). Other agents with known or
                          potential antituberculosis activity should be
                          avoided, including the following: 1.
                          Aminosalicylic acid salts 2. Capreomycin 3.
                          Clofazimine 4. Cycloserine 5. Ethambutol 6.
                          Ethionamide 7. Isoniazid 8. Kanamycin 9.
                          Pyrazinamide 10. Rifabutin 11. Rifampin 12.
                          Streptomycin 13. Thiacetazone.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions or symptoms are excluded: 1.
                          Current active tuberculosis (confirmed or
                          suspected). 2. Sensitivity or intolerance to
                          study medication. 3. Acute hepatitis. 4.
                          Evidence of peripheral neuropathy, i.e.,
                          signs or symptoms of paresis, paresthesias,
                          neuromotor abnormalities, or neurosensory
                          deficits of grade 3 or worse. 5. Inability to
                          have concomitant medications changed to avoid
                          serious interaction with study drug.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0109  Rifampin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0124  Pyrazinamide
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0123  Isoniazid
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0125  Pyridoxine
TRADE NAME OF SUBSTANCE   Drug 1 Rifadin
MANUFACTURERS             Drug 1: Marion Merrell Dow Medical
                          Information / PO Box 9627 Kansas City, MO
                          64134-0627 Contact: Medical Information (800)
                          633-1610.
MANUFACTURERS             Drug 2: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
MANUFACTURERS             Drug 3: Barr Laboratories Incorporated 2
                          Quaker Road PO Box D-2900 Pomona, NY 10970
                          Contact: Harold Cohen (914) 362-1100 X 2823.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 450 mg (if 25-49 kg)
                          or 600 mg (if 50 kg or greater) daily x 60
                          days. Drug 2: 20 mg/kg (maximum 3000 mg)
                          daily in 3-4 divided doses fdays. Drug 3: 300
                          mg daily for 12 months. Drug 4: 50 mg daily
                          for 12 months
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 450 or 600 mg. Drug 2:
                          20 mg/kg. Drug 3: 300 mg. Drug 4: 50 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 150 and 300 mg
                          capsules. Drug 2: Oral, 500 mg tablets. Drug
                          3: Oral, 300 mg tablets. Drug 4: Oral, 50 mg
                          tablets
OTHER TREATMENT INFO.     END POINT: Primary end point: Time to
                          development of confirmed active pulmonary or
                          extrapulmonary tuberculosis, supported by
                          more inclusive analyses using probable
                          tuberculosis with confirmed tuberculosis.
                          Secondary end point: Combined end point of
                          death and confirmed or probable active
                          tuberculosis, toxicity from treatment, and
                          laboratory findings.
OTHER TREATMENT INFO.     DISCONTINUE: Patients will be removed from
                          the study for the following reasons: 1. Grade
                          4 toxicity at the discretion of the primary
                          physician. 2. Development of any confirmed or
                          probable active pulmonary or extrapulmonary
                          tuberculosis. 3. Development of severe
                          clinical hepatitis due to study drug. 4.
                          Development of Mycobacterium avium infection
                          requiring continuous, chronic, or recurrent
                          treatment with agents active in the treatment
                          of tuberculosis at the discretion of the
                          investigator. 5. Persistent or recurring
                          serious study drug toxicity despite temporary
                          drug discontinuation. 6. Pregnancy (ONLY if
                          on the rifampin/pyrazinamide arm).
OTHER TREATMENT INFO.     MODIFICATION: For grade 2 toxicities, study
                          drugs may be temporarily withheld at the
                          investigator's discretion. For grade 3
                          toxicity that is possibly related to study
                          drug, withhold study drug. Depending on the
                          nature and severity of the toxicity, the
                          degree to which it resolved, and/or the
                          emergence of alternative explanations for the
                          toxicity or the patient's deterioration, the
                          study drug may be restarted at the discretion
                          of the primary physician. For any grade 4
                          toxicity, the study drug will be temporarily
                          withheld and may be permanently stopped at
                          the discretion of the primary physician.
                          Study drug will be temporarily withheld for:
                          1. Development of mild to moderate toxicity.
                          2. Development of moderate clinical hepatitis
                          due to study drug (rechallenge of study drug
                          will occur at the discretion of the
                          investigator). 3. Development of clinical
                          hepatitis due to reasons other than study
                          drug. 4. Treatment for acute opportunistic
                          infection or malignancy requiring temporary
                          cessation of study medication at the
                          investigator's discretion.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (CPCRA).
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antitubercular Agents/ADMINISTRATION & DOSAGE/
                          *THERAPEUTIC USE
MESH HEADING              Drug Evaluation
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Isoniazid/ADMINISTRATION & DOSAGE/THERAPEUTIC
                          USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Multicenter Studies
MESH HEADING              Opportunistic Infections/COMPLICATIONS/
                          PREVENTION & CONTROL
MESH HEADING              Pyrazinamide/ADMINISTRATION & DOSAGE/
                          THERAPEUTIC USE
MESH HEADING              Pyridoxine/ADMINISTRATION & DOSAGE/
                          THERAPEUTIC USE
MESH HEADING              Rifampin/ADMINISTRATION & DOSAGE/*THERAPEUTIC
                          USE
MESH HEADING              Tuberculosis/COMPLICATIONS/*PREVENTION &
                          CONTROL
CAS REGISTRY NUMBER       0 (Antitubercular Agents)
CAS REGISTRY NUMBER       13292-46-1 (Rifampin)
CAS REGISTRY NUMBER       54-85-3 (Isoniazid)
CAS REGISTRY NUMBER       65-23-6 (Pyridoxine)
CAS REGISTRY NUMBER       98-96-4 (Pyrazinamide)
LAST REVISION DATE        941207
ENTRY MONTH               9111
CALIFORNIA                Community Consortium of San Francisco 3180
                          18th Street Suite 201 San Francisco, CA 94110
                          Contact: Thomas Mitchell (415) 476-9554 OPEN
                          911202.
COLORADO                  Denver / CPCRA 605 Bannock Street Denver, CO
                          80204-4507 Contact: Jack Rouff (303) 436-7184
                          Contact: (303) 436-7224 OPEN 911202.
CONNECTICUT               Hill Health Corporation 400-428 Columbus
                          Avenue New Haven, CT 06519 Contact: Adrienne
                          Joy Burns (203) 776-9594 OPEN 911202.
DISTRICT OF COLUMBIA      Washington Regional AIDS Program 50 Irving St
                          N W / Room ID-151B Washington, DC 20422
                          Contact: John Scott (202) 745-8695 OPEN
                          911202.
DELEWARE                  Delaware / CPCRA 501 West 14th Street
                          Wilmington, DE 19899 Contact: Arlene Bincsik
                          (302) 428-2538 OPEN 911202.
GEORGIA                   Atlanta AIDS Research Consortium Incorporated
                          131 Ponce deLeon Suite 220 Atlanta, GA 30308
                          Contact: Amy Morris (404) 876-2317 OPEN
                          930203.
ILLINOIS                  Chicago Department of Health / Speciality STD
                          Clinic 1306 South Michigan Avenue Chicago, IL
                          60605 Contact: James R. Dickes (312) 747-0120
                          OPEN 930414.
ILLINOIS                  Chicago CPCRA 711 West North Avenue Suite 201
                          Chicago, IL 60610 Contact: Jeffrey Zurlinden
                          (312) 266-0227 OPEN 911202.
LOUISIANA                 Louisiana Community AIDS Research Program
                          1430 Tulane Avenue New Orleans, LA 70112
                          Contact: Ermelle Martinez Laurent (504)
                          584-1971 OPEN 911202.
MASSACHUSETTS             Boston Department of Health and Hospitals
                          1010 Massachusetts Avenue / Second Floor
                          Boston, MA 02118 Contact: Dr Hermide Pierre
                          Mercier (617) 534-5916 OPEN 930513.
MARYLAND                  Brazil / Johns Hopkins University 615 North
                          Wolfe Street / Room 5515 Baltimore, MD 21205
                          Contact: Dr Mauro Schecter (410) 955-6964
                          OPEN 930408.
MARYLAND                  Johns Hopkins University / School of Hygiene
                          & Public Hlth 615 North Wolfe Street / Room
                          5515 Baltimore, MD 21205-2179 Contact:
                          Jacqueline S. Coberly (410) 955-7767 Contact:
                          (410) 955-6964 OPEN 930423.
MICHIGAN                  Comprehensive AIDS Alliance of Detroit 4160
                          John R / Harper Hospital Prof Bldg / Suite
                          202 Detroit, MI 48201 Contact: Constance
                          Rowley (313) 993-0934 OPEN 911202.
MICHIGAN                  Henry Ford Hospital 2799 West Grand Boulevard
                          Detroit, MI 48202 Contact: Diane Mastro-Polak
                          (313) 876-7664 OPEN 920210.
NEW JERSEY                Community Research Initiative of North Jersey
                          393 Central Avenue Newark, NJ 07102 Contact:
                          William Orr (201) 648-0350 Contact: Vicki
                          Taylor Contact: Dr George Perez OPEN 911202.
NEW JERSEY                Saint Michaels Medical Center 267 Martin
                          Luther King Boulevard / c/o OCRE / mailstop
                          73B Newark, NJ 07102 Contact: Sung Poblete
                          (201) 877-2960 OPEN 930408.
NEW JERSEY                North Jersey Community Research Initiative
                          657 King Boulevard Newark, NJ 07102 Contact:
                          Victoria Taylor (201) 648-0350 OPEN 920706.
NEW JERSEY                W C Lattimore Comprehensive Pulmonary Disease
                          Clinic Martland Building / GA 43 / 65 Bergen
                          Street Newark, NJ 07103 Contact: Sandi Barnes
                          (201) 982-6232 OPEN 930420.
NEW YORK                  Beth Israel Medical Center / MMTP / Tb
                          Interim Clinic / Third Floor / 103 East 125th
                          Street New York, NY 10035 Contact: Sara Back
                          (212) 427-9541 X 206OPEN 930408.
NEW YORK                  Harlem AIDS Treatment Group Harlem Hospital /
                          Women's Pavilion Room 126 New York, NY 10037
                          Contact: Joshua Standig (212) 939-2951 OPEN
                          911202.
NEW YORK                  Bronx-Lebanon Hospital Center 1309 Fulton
                          Avenue Bronx, NY 10456 Contact: Cathy Pollard
                          (718) 293-2593 Contact: (718) 901-8916 OPEN
                          920511.
NEW YORK                  Addiction Research And Treatment Corporation
                          22 Chapel Street Brooklyn, NY 11201 Contact:
                          Dr Robert Sawyer (718) 260-2917 OPEN 911202.
NEW YORK                  Clinical Directors Network of Region II 5601
                          2nd Avenue #3 Brooklyn, NY 11220 Contact:
                          Linda Podhurst (212) 255-3841 OPEN 911202.
 
13
UNIQUE IDENTIFIER         NIH/00626
PROTOCOL ID NUMBERS       NIAID ACTG 281
PROTOCOL TITLE            HPMPC ( Cidofovir ) Peripheral CMV Retinitis
                          Trial Protocol.
VERSION NUMBER & DATE     1 (940316)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate short-term and long-term
                          safety and efficacy of intravenous cidofovir
                          (HPMPC) for treatment of small peripheral
                          cytomegalovirus (CMV) retinitis lesions. To
                          provide data on the relative safety and
                          efficacy of 3 mg/kg versus 5 mg/kg HPMPC as
                          maintenance regimens. Methodology: In Stage
                          1, up to 30 patients are randomized to either
                          observation with deferral of treatment until
                          the retinitis progresses (observation group),
                          or to intravenous HPMPC at 5 mg/kg for two
                          consecutive weekly induction doses, followed
                          by 3 mg/kg every other week for maintenance.
                          In Stage 2, up to 70 patients are randomized
                          to observation or to HPMPC at 5 mg/kg for two
                          consecutive weekly induction doses followed
                          by either 3 or 5 mg/kg every other week for
                          maintenance, for a total of three treatment
                          groups. Concomitant saline hydration and
                          probenecid are administered to patients
                          receiving HPMPC.
GENERAL DESCRIPTION       METHODOLOGY: In Stage 1, up to 30 patients
                          are randomized to either observation with
                          deferral of treatment until the retinitis
                          progresses (observation group), or to
                          intravenous HPMPC at 5 mg/kg for two
                          consecutive weekly induction doses, followed
                          by 3 mg/kg every other week for maintenance.
                          In Stage 2, up to 70 patients are randomized
                          to observation or to HPMPC at 5 mg/kg for two
                          consecutive weekly induction doses followed
                          by either 3 or 5 mg/kg every other week for
                          maintenance, for a total of three treatment
                          groups. Concomitant saline hydration and
                          probenecid are administered to patients
                          receiving HPMPC.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS by CDC criteria. 2. CMV
                          retinitis as determined by a SOCA-certified
                          ophthalmologist, with small lesions involving
                          < 25 percent of the total area of the retina
                          and confined to the periphery of the retina,
                          located at least 1500 microns from the margin
                          of the optic disc and 3000 microns from the
                          center of the fovea (entirely in zones 2 or
                          3). 3. At least one lesion whose size is
                          one-quarter disc area or greater that can be
                          photographed. 4. Visual acuity in an affected
                          eye of three or more lines on the ETDRS
                          (Early Treatment Diabetic Retinopathy Study)
                          chart at 1 meter distance (Snellen equivalent
                          8/200). 5. NO retinal detachment in the
                          affected eye(s). 6. NO extraocular CMV
                          disease. 7. NO media opacity that precludes
                          visualization of the fundus of both eyes.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    FDA 231A. GS-93-105
STUDY DESIGN              2-Stage; Randomized
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS by CDC criteria. 2. CMV
                          retinitis as determined by a SOCA-certified
                          ophthalmologist, with lesion size, location,
                          and severity as specified in the Disease
                          Status field. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          < 1+ proteinuria on urinalysis.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prophylaxis with
                          anti-CMV agents.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Oral
                          trimethoprim/sulfamethoxazole. 2. Aerosolized
                          pentamidine. 3. Dapsone. 4. Fluconazole. 5.
                          Ketoconazole. 6. Itraconazole. 7. Rifabutin.
                          8. Filgrastim (G-CSF). 9. Antiretroviral
                          agents.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of renal disease or renal dialysis.
                          2. History of clinically significant cardiac
                          disease, including symptoms of ischemia,
                          congestive heart failure, or arrhythmia. 3.
                          History of clinically significant probenecid
                          allergy. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control during study and for 90 days
                          after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Drug or alcohol abuse
                          sufficient to hinder compliance with study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior therapy
                          for CMV disease with ganciclovir, foscarnet,
                          CMV hyperimmune immunoglobulin, or other
                          investigational agents with anti-CMV
                          activity. 2. Therapy with nephrotoxic drugs
                          within the past 7 days, including
                          amphotericin B, aminoglycoside antibiotics,
                          vidarabine, and intravenous pentamidine.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Ongoing
                          therapy for CMV disease with ganciclovir,
                          foscarnet, CMV hyperimmune immunoglobulin, or
                          other investigational agents with anti-CMV
                          activity. 2. Therapy with nephrotoxic drugs,
                          including amphotericin B, aminoglycoside
                          antibiotics, vidarabine, and intravenous
                          pentamidine.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0145  HPMPC
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0053  Probenecid
TRADE NAME OF SUBSTANCE   Drug 1 GS-0504
MANUFACTURERS             Drug 1: Gilead Sciences Incorporated 353
                          Lakeside Drive Foster City, CA 94404 Contact:
                          Dr Robert Stagg (415) 572-6566.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 5 mg/kg for two
                          consecutive weekly induction doses, followed
                          by 3 or 5 mg/kg every other week for
                          maintenance. Drug 2: Administered
                          concurrently with HPMPC
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Gilead Sciences
                          Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Cytosine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Organophosphorus Compounds/ADMINISTRATION &
                          DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       113852-37-2
                          (1-(3-hydroxy-2-phosphonylmethoxypropyl)cytos-
                          ine)
LAST REVISION DATE        941207
ENTRY MONTH               9405
MARYLAND                  Johns Hopkins University / SOCA 615 North
                          Wolfe Street Room 5010 Baltimore, MD 21205
                          Contact: Janet Holbrook (410) 955-8175
                          Contact: (410) 955-0930 OPEN 940506.
 
14
UNIQUE IDENTIFIER         NIH/00643
PROTOCOL ID NUMBERS       NIAID ACTG 277
PROTOCOL TITLE            A Randomized, Comparative Study of Daily
                          Dapsone and Daily Atovaquone for Prophylaxis
                          Against PCP in HIV-Infected Patients Who Are
                          Intolerant of Trimethoprim and/or
                          Sulfonamides.
VERSION NUMBER & DATE     2 (940701)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  El-Sadr W
PROTOCOL CHAIRS           CO-CHAIR  Luskin-Hawk R, Murphy R
GENERAL DESCRIPTION       PURPOSE: To compare the efficacy and safety
                          of dapsone versus atovaquone in preventing or
                          delaying the onset of histologically proven
                          or probable pneumocystis carinii pneumonia in
                          HIV-infected patients with CD4 counts <= 200
                          cells/mm3 or <= 15 percent of the total
                          lymphocyte count who are intolerant to
                          trimethoprim and/or sulfonamides.
GENERAL DESCRIPTION       RATIONALE: Trimethoprim/sulfamethoxazole
                          (TMP/SMX), which is effective for secondary
                          PCP prophylaxis, is associated with allergic
                          manifestations and side effects that limit
                          its use. Patients who are intolerant of
                          TMP/SMX require an effective alternative.
                          Dapsone and atovaquone have both shown
                          promise as PCP prophylactic agents.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either dapsone or atovaquone daily,
                          with follow-up at the clinic every 4 months.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Working diagnosis of HIV
                          infection based on medical history,
                          behavioral history, clinical signs and
                          symptoms, or laboratory test results. 2. CD4
                          count <= 200 cells/mm3 or <= 15 percent of
                          total lymphyocyte count at any time in the
                          past OR a history of PCP. 3. History of
                          intolerance of trimethoprim and/or
                          sulfonamides that required permanent
                          discontinuation.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    CPCRA 034. IND 45,799
STUDY DESIGN              Randomized; Comparative; Multicenter; 2-Arm;
                          Drug Comparison; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug safety,
                          Drug efficacy, Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 700 patients. (350
                          patients per treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 20
                          months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 269/700 (941207).
PROTOCOL DETAILS          STUDY DURATION: 32 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 74 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Working diagnosis of HIV infection.
                          2. CD4 count <= 200 cells/mm3 or <= 15
                          percent of total lymphyocyte count at any
                          time in the past OR a history of PCP. 3.
                          History of intolerance of trimethoprim and/or
                          sulfonamides that required permanent
                          discontinuation. NOTE: Pregnant patients are
                          eligible at the clinician's discretion.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 200 cells/mm3. OR <=
                          fifteen percent of the total lymphocyte count
                          at any time in the past. ( 0 - 100 - 200 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          Adequate G6PD (normal or elevated).
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior PCP
                          prophylaxis.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Strongly recommended:
                          Pyrimethamine (50 mg) and folinic acid (15
                          mg) weekly in patients receiving dapsone who
                          have CD4 count < 100 cells/mm3 and are
                          toxoplasmosis seropositive.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Known treatment-limiting reaction to dapsone
                          or atovaquone. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: PCP
                          prophylaxis (other than study drug) or any
                          medication with potential anti-PCP activity.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Active
                          pneumocystosis.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0036  Dapsone
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0084  Atovaquone
MANUFACTURERS             Drug 1: Jacobus Pharmaceutical Company PO Box
                          5290 / 37 Cleveland Lane Princeton, NJ 08540
                          Contact: Dr David Jacobus (609) 921-7447
                          Contact: Dr Neil Lewis (609) 921-7447.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 mg daily. Drug
                          2: 1500 mg daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 100 mg. Drug 2: 1500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 25 and 100 mg
                          tablets. Drug 2: Oral, 750 mg/5 ml foil
                          sachets
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 20 months.
OTHER TREATMENT INFO.     END POINT: Primary: Occurrence/recurrence of
                          morphologically or histologically proven PCP
                          or probable PCP. Secondary: Toxicity;
                          incidence of PCP, extrapulmonary
                          pneumocystosis, and death; development of
                          toxoplasmosis; death.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity to the assigned study drug, with
                          inability of patient to switch over to the
                          alternate regimen. 2. Development of
                          toxoplasmosis. 3. Patient has reached a
                          switchpoint but has exhausted switchover
                          alternatives. 4. Deemed in the best interest
                          of patient to discontinue study therapy. 5.
                          Refusal of patient to continue therapy. 6.
                          Termination of the study.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Dapsone/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Naphthoquinones/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *PREVENTION & CONTROL
CAS REGISTRY NUMBER       80-08-0 (Dapsone)
CAS REGISTRY NUMBER       94015-53-9 (atovaquone)
LAST REVISION DATE        941207
ENTRY MONTH               9410
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 941201 ACTU: 5801.
ALABAMA                   Dr John Dunkel 101-A Bob Wallace Avenue
                          Huntsville, AL 35801 Contact: Dr John Dunkel
                          (205) 533-6558 OPEN 941020.
CALIFORNIA                Children's Hospital of Los Angeles /
                          Children's AIDS Center 4650 Sunset Blvd /
                          Mail Stop #54 Los Angeles, CA 90027 Contact:
                          Antonieta Sosa (213) 669-2180 OPEN 941110
                          ACTU: 9916.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          941116 ACTU: 1201.
CALIFORNIA                USC Univ Hosp & Ambulatory Health Care Center
                          2020 Zonal Avenue / Room 309 Los Angeles, CA
                          90033-1079 Contact: Luis Mendez (213)
                          343-8288 OPEN 941116 ACTU: 1204.
CALIFORNIA                University of California San Diego 9500
                          Gilman Drive / Clinical Sciences Bldg
                          LaJolla, CA 92093-0672 Contact: Candace
                          McIvor (619) 534-7170 OPEN 941103 ACTU: 0701.
CALIFORNIA                AIDS Community Research Consortium 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harris (415) 364-5653 OPEN
                          941017 ACTU: 0505.
CALIFORNIA                Santa Clara Valley Med Ctr / ACRC 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harriss (415) 364-5653 OPEN
                          941017 ACTU: 0506.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840OPEN 941103 ACTU: 0801.
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 941205 ACTU: 0808.
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          941104 ACTU: 0802.
CALIFORNIA                Community Consortium of San Francisco 3180
                          18th Street Suite 201 San Francisco, CA 94110
                          Contact: Thomas Mitchell (415) 476-9554 OPEN
                          941019.
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 941014
                          ACTU: 0501.
CALIFORNIA                Merrit-Peralta Medical Ctr/Adult Immunology
                          Clinic U of CA 450 30th Street Oakland, CA
                          94609 Contact: Bruce Ross (510) 273-8200
                          Contact: David Greenberg OPEN 941123 ACTU:
                          0804.
COLORADO                  Denver / CPCRA 605 Bannock Street Denver, CO
                          80204-4507 Contact: Jack Rouff (303) 436-7184
                          Contact: (303) 436-7224 OPEN 941031.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 941003 ACTU:
                          6101.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941024 ACTU:
                          6104.
COLORADO                  Kaiser Permanente Franklin Med Cntr / Univ
                          Col Hlth Sci Cntr 4200 East Ninth Avenue /
                          Colorado ACTU / Campus Box B-163 Denver, CO
                          80262 Contact: Graham Ray (303) 270-8551
                          Contact: FAX (303) 270-6102 OPEN 941003 ACTU:
                          6103.
COLORADO                  Denver Department of Health and Hospitals /
                          Univ of CO Colorado ACTU / Campus Box B 163 /
                          4200 East Ninth Avenue Denver, CO 80262
                          Contact: M Graham Ray (303) 270-8551 OPEN
                          941003 ACTU: 6102.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 941123 ACTU: 5701.
DISTRICT OF COLUMBIA      HIV Center - DC General Hospital / Georgetown
                          Univ Med Ctr Kober-Cogan 110 / 3800 Reservoir
                          Road NW Washington, DC 20007-2197 Contact:
                          Karen Gammon (202) 687-1079 Contact: Fax
                          (202) 687-6476 OPEN 941122 ACTU: 5703.
DISTRICT OF COLUMBIA      Whitman-Walker Clinic / Georgetown Univ
                          Medical Center Kober-Cogan 110 / 3800
                          Reservoir Road NW Washington, DC 20007-2197
                          Contact: Karen Gammon (202) 687-1079 Contact:
                          Fax (202) 687-6476 OPEN 941207 ACTU: 5702.
DISTRICT OF COLUMBIA      Washington Regional AIDS Program 50 Irving St
                          N W / Room ID-151B Washington, DC 20422
                          Contact: John Scott (202) 745-8695 OPEN
                          941011.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 941006
                          ACTU: 0901.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          deLeon Suite 220 Atlanta, GA 30308 Contact:
                          Amy Morris (404) 577-2311 OPEN 941123.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 941117
                          ACTU: 5201.
ILLINOIS                  Chicago CPCRA 711 West North Avenue Suite 201
                          Chicago, IL 60610 Contact: Jeffrey Zurlinden
                          (312) 266-0227 OPEN 941017.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940923 ACTU: 2701.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 941104 ACTU: 2702.
ILLINOIS                  Cook County Hospital Passavant Pavilion /
                          Room 823 / 303 East Superior Chicago, IL
                          60611 Contact: Baiba L Berzins (312) 908-9636
                          OPEN 941205 ACTU: 2705.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941017 ACTU: 2708.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 941007 ACTU: 2601.
LOUISIANA                 Louisiana Community AIDS Research Program
                          Tulane University Medical Center / 1430
                          Tulane Avenue, HC28 New Orleans, LA 70112
                          Contact: Janice Walker (504) 584-1971
                          Contact: Fax (504) 584-1972 OPEN 941123.
MASSACHUSETTS             Massachusetts General Hospital / Harvard 55
                          Fruit Street Gray 5 Boston, MA 02114 Contact:
                          Ellen Godfrey (617) 726-5598 OPEN 941205
                          ACTU: 0101.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02115 Contact: Sheila Hussey (617)
                          735-4103 OPEN 941123 ACTU: 0102.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 941018 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 941115 ACTU:
                          0202.
MICHIGAN                  Henry Ford Hospital 2799 West Grand Boulevard
                          Detroit, MI 48202 Contact: Diane Mastro-Polak
                          (313) 876-7664 OPEN 941121.
MINNESOTA                 St Paul-Ramsey Medical Center 640 Jackson
                          Street St Paul, MN 55101 Contact: Ray Nelson
                          (612) 221-1280 OPEN 941031 ACTU: 1503.
MINNESOTA                 Hennepin County Med Clinic / Univ of
                          Minnesota Hosp Clinic 420 Delaware Street SE
                          / Room G255 Mayo Building Minneapolis, MN
                          55415 Contact: Renee St Jacques (612)
                          373-1810 OPEN 941014 ACTU: 1502.
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 941014 ACTU:
                          1501.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 941003 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 941003
                          ACTU: 2102.
NORTH CAROLINA            Moses H Cone Memorial Hospital / University
                          North Carolina 1200 North Elm Street
                          Greensboro, NC 27401 Contact: Pam Mentley
                          (910) 574-7888 OPEN 941017 ACTU: 3203.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          940923 ACTU: 3201.
NORTH CAROLINA            Wake County Department of Health Hosp South
                          Room 0207 Box 3284 Durham, NC 27710 Contact:
                          Kelley Rayle (919) 250-1035 OPEN 941103 ACTU:
                          3206.
NORTH CAROLINA            Carolinas Medical Center / Department of
                          Internal Medicine 1000 Blythe Blvd AHEC Room
                          507 Charlotte, NC 28203 Contact: Joan Connell
                          (704) 355-5292 Contact: (704) 355-3165 OPEN
                          941007 ACTU: 3204.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Frances Tennant (402) 559-5750 OPEN
                          941104 ACTU: 1505.
NEW JERSEY                North Jersey Community Research Initiative
                          657 King Boulevard Newark, NJ 07102 Contact:
                          Victoria Taylor (201) 648-0350 OPEN 941031.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 941017 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 941003 ACTU: 0401.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          941031 ACTU: 1801.
NEW YORK                  Harlem AIDS Treatment Group / Harlem Hospital
                          Center Womens Pavilion Room 126 / 506 Lenox
                          Avenue New York, NY 10037 Contact: Luis
                          Fuentes (212) 649-4343 OPEN 941026.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 941007
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 941007 ACTU: 1901.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 941116 ACTU: 1903.
NEW YORK                  Bronx Veterans Administration Medical Center
                          130 West Kingsbridge Road Bronx, NY 10468
                          Contact: Nancy Ostrow (718) 584-9000 X
                          667Contact: (718) 584-9000 X 667OPEN 941201
                          ACTU: 1804.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          941005 ACTU: 7403.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 941005 ACTU: 7401.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          941005 ACTU: 7402.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 941123 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941003 ACTU: 1102.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 941031 ACTU: 1101.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941013
                          ACTU: 2301.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940930 ACTU: 2501.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn / Suite 770 Portland, OR 97210
                          Contact: Joyce St Arnaud (503) 229-8428 OPEN
                          941101.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 941018 ACTU: 6201.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 941104 ACTU: 6202.
SOUTH CAROLINA            Medical University of SC / Infect Diseases
                          Division 807 CSB 171 Ashley Avenue
                          Charleston, SC 29425 Contact: Denise Taylor
                          (803) 782-6174 OPEN 941024 ACTU: 3205.
 
15
UNIQUE IDENTIFIER         NIH/00671
PROTOCOL ID NUMBERS       NIAID ACTG 275
PROTOCOL TITLE            A Phase II Randomized, Double-Blind,
                          Placebo-Controlled Trial of the Virologic
                          Effect of Two Different Nucleoside Treatment
                          Strategies (Zidovudine Versus Zidovudine in
                          Combination With Didanosine) for HIV
                          Infection in Subjects With CD4+ Counts >= 550
                          Cells/mm3.
VERSION NUMBER & DATE     1 (940922)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Erice A
PROTOCOL CHAIRS           CO-CHAIR  Balfour H, Carey J, Henr
GENERAL DESCRIPTION       PURPOSE: To determine the effects of
                          zidovudine (AZT) alone and in combination
                          with didanosine (ddI) on viral load in the
                          lymphoid tissue and blood of
                          antiretroviral-naive, HIV-infected patients
                          with CD4 counts >= 550 cells/mm3.
GENERAL DESCRIPTION       RATIONALE: Recent studies have shown that
                          during the asymptomatic phase (clinical
                          latency) of HIV infection, there is an
                          extraordinarily large number of infected CD4+
                          lymphocytes and macrophages throughout the
                          lymphoid system, both in latent and
                          productive states. These findings support the
                          belief that early intervention therapy with
                          reverse transcriptase inhibitors could
                          prolong the clinical latency period.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive AZT alone, AZT plus ddI, or no
                          therapy (placebo) daily for 48 weeks.
                          Patients are followed at weeks 2, 4, and 8,
                          and then every 8 weeks thereafter until week
                          48.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA
                          confirmed by a) Western blot, positive HIV
                          antigen, or positive HIV culture; or b) a
                          second antibody test other than ELISA. 2. CD4
                          count >= 550 cells/mm3 within 30 days prior
                          to study entry. 3. Asymptomatic by CDC
                          criteria.
ELIGIBILITY               ASYM.
OTHER PROTOCOL NUMBERS    IND 35,208
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Multicenter; 3-Arm; Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Combination and
                          single drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 105 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 50 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. CD4 count >=
                          550 cells/mm3. 3. No ARC or AIDS conditions
                          by CDC criteria. 4. Consent of parent or
                          guardian if less than 18 years of age. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 12 g/dl. (men); >= 11.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 550 cells/mm3. ( 600
                          - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 75 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. Alkaline phosphatase <= 5 x ULN.
                          Total serum amylase <= 1.5 x ULN (if serum
                          amylase > 1.5 x ULN, then lipase <= 1.5 x ULN
                          or pancreatic amylase <= 1.5 x ULN is
                          acceptable).
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: 1. Radiation
                          therapy to local lesion only. 2. Acupuncture.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antibiotics for bacterial infections as
                          clinically indicated. 2. Recombinant
                          erythropoietin (EPO) and G-CSF as clinically
                          indicated for grade 3 or worse anemia and
                          neutropenia, respectively. 3. Antipyretics.
                          4. Analgesics. 5. Allergy medications. 6.
                          Oral contraceptives. 7. Nonprescription
                          medications such as vitamins or herbal
                          therapies.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of chronic diarrhea, defined as more
                          than four loose or watery stools on average
                          daily for the past month. 2. History of grade
                          2 or worse peripheral neuropathy. 3. History
                          of pancreatitis. 4. Bacterial infection
                          requiring antibiotics within 14 days prior to
                          study entry. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse or
                          alcoholism.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 2 weeks
                          prior to study entry: Transfusion.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy except to local lesion.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Prior HIV therapy
                          with antiretrovirals or systemic
                          immunomodulators.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          antiretrovirals or systemic immunomodulators.
                          2. Systemic corticosteroids. 3. Systemic
                          cytotoxic chemotherapy. 4. Intravenous
                          pentamidine.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Presence of factors predisposing to
                          pancreatitis such as active alcoholism. 2.
                          Other medical conditions that would interfere
                          with study compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 Videx
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or placebo)
                          TID for 48 weeks. Drug 2: 200 mg (or placebo)
                          BID for 48 weeks (125 mg BID if les60 kg body
                          weight)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 400 mg
                          (250 mg if less than 60 kg body weight)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules.
                          Drug 2: Oral; 25, 50, and 100 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Virologic and immunologic
                          parameters.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Decrease in CD4 count to <= 50
                          percent of baseline on repeat testing. 3.
                          Development of AIDS-indicator conditions. 4.
                          Pregnancy. 5. Further participation
                          considered detrimental to patient's health or
                          well-being. 6. Requirement for medications
                          not allowed on this study. 7. Patient
                          noncompliance or refusal of further
                          treatment.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 drug-related
                          toxicity other than myositis,
                          hyperamylasemia, anemia, neutropenia, or
                          peripheral neuropathy: Hold study drugs until
                          toxicity resolves to grade 2 or better, then
                          resume at 50 percent dose. For grade 4
                          toxicity other than myositis,
                          hyperamylasemia, anemia, or neutropenia: Hold
                          study drugs until toxicity resolves to grade
                          3 or better, then resume at reduced dose
                          following consultation with an ACTG
                          physician, patient, study chair, and
                          patient's personal physician. For grade 2 or
                          3 peripheral neuropathy: Hold study drugs
                          until toxicity resolves to grade 1 or better,
                          then resume AZT at full dose and ddI at 50
                          percent dose. For grade 3 or 4 myositis,
                          hyperamylasemia, anemia, or neutropenia:
                          Depending on specific toxicity, hold one or
                          both study drugs until toxicity resolves to
                          acceptable levels, then resume at full or
                          reduced dose.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9412
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 941118 ACTU:
                          1501.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 941123 ACTU: 2501.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 941205 ACTU: 6202.
 
16
UNIQUE IDENTIFIER         NIH/00657
PROTOCOL ID NUMBERS       NIAID ACTG 269
PROTOCOL TITLE            Phase II Evaluation of Low-Dose Oral
                          Etoposide for the Treatment of Relapsed or
                          Progressed AIDS-Related Kaposi's Sarcoma
                          After Systemic Chemotherapy.
VERSION NUMBER & DATE     1 (940819)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Von Roenn JH
PROTOCOL CHAIRS           CO-CHAIR  Paredes J
GENERAL DESCRIPTION       PURPOSE: To assess the toxicity, tumor
                          response rate, and effect on quality of life
                          of daily low-dose etoposide administered for
                          7 consecutive days every other week in
                          patients with AIDS-related Kaposi's sarcoma
                          that has relapsed or progressed after
                          systemic chemotherapy.
GENERAL DESCRIPTION       RATIONALE: Etoposide may be at least as, or
                          even more, effective and less myelotoxic when
                          given in low doses over prolonged periods of
                          time.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive low-dose (50
                          mg) oral etoposide on days 1 through 7 of
                          every 2-week cycle. Patients who achieve a
                          complete or partial response after two cycles
                          and have no toxicity greater than grade 2 may
                          have their dose escalated to 100 mg for
                          subsequent cycles. If there are no responses
                          to therapy among the first 14 evaluable
                          patients, the study will close; if there is
                          at least one objective response to therapy
                          among the first 14 evaluable patients,
                          enrollment will continue until all 41
                          patients are enrolled. Patients continue
                          therapy until maximal tumor response (either
                          stable disease or complete response) is
                          achieved or disease progression occurs.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (941207)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot. 2. Biopsy-proven
                          Kaposi's sarcoma that has relapsed or
                          progressed following non-investigational
                          systemic chemotherapy with at least two
                          agents. 3. Mucocutaneous lesions (15 or more)
                          and/or symptomatic mucosal lesions and/or
                          visceral Kaposi's sarcoma (symptomatic
                          lymphadema qualifies patients in the absence
                          of these three conditions). 4. NO active
                          acute opportunistic infections requiring
                          treatment with myelosuppressive antibiotics
                          (maintenance for OIs is permitted).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 34,080
STUDY DESIGN              Open Label; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 41 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least two
                          cycles.
PROTOCOL DETAILS          STUDY DURATION: Indefinite.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Kaposi's sarcoma
                          that has relapsed or progressed. 3.
                          Mucocutaneous lesions (15 or more) and/or
                          symptomatic mucosal lesions and/or visceral
                          Kaposi's sarcoma (symptomatic lymphadema
                          qualifies patients in the absence of these
                          three conditions). 4. NO active acute
                          opportunistic infections requiring treatment
                          with myelosuppressive antibiotics
                          (maintenance for OIs is permitted). 5.
                          Consent of parent or guardian if less than 18
                          years of age. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 5 x ULN.
                          Absolute neutrophils >= 1000 cells/mm3.
PATIENT AGE               AGE: 12 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Maintenance
                          therapy for opportunistic infections.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          Neuropsychiatric history. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 11 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Continued alcohol consumption
                          or continued intravenous drug use that would
                          impair ability to comply with study
                          requirements.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 7 days prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          etoposide. 2. Any other anti-KS drugs within
                          14 days prior to study entry. 3. Any
                          investigational drug other than
                          antiretrovirals within 14 days prior to study
                          entry. 4. Any prior investigational agent, if
                          given as the ONLY prior treatment for KS.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Other
                          active malignancies except basal cell
                          carcinoma of the skin, or carcinoma in situ
                          of the cervix. 2. Grade 3 or worse peripheral
                          neuropathy. 3. Altered mental status that
                          would prevent informed consent or prevent
                          study compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0081  Etoposide
MANUFACTURERS             Drug 1: Bristol-Myers Squibb Company PO Box
                          4500 Princeton, NJ 08543-4500 Contact: Sharon
                          Duncan (609) 897-2126.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 50 mg daily on days
                          1 through 7 every 2 weeks for a minimum of 2
                          cycles, with escalation to 100 mg in
                          subsequent cyif patient achieves partial or
                          complete response with no toxicigrade 2
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 50 or 100 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 50 mg capsules
OTHER TREATMENT INFO.     END POINT: Complete and partial response
                          rates.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Development of opportunistic
                          infection that precludes further treatment on
                          study. 3. Development of other malignancies
                          requiring radiation or systemic therapy. 4.
                          Granulocytes < 1000 cells/mm3 or platelets <
                          75000 cells/mm3 persisting for more than 2
                          weeks after study therapy is held for
                          hematologic toxicity. 5. Progressive disease
                          after two cycles. 6. Considered to have
                          reached maximal tumor response. 7. Study drug
                          is held for more than 21 days. 8. Pregnancy.
                          9. Patient noncompliance or desire of patient
                          to withdraw. 10. Further study therapy deemed
                          detrimental to patient's health.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 or 4 hematologic
                          toxicity: Hold study drug until toxicity
                          resolves to grade 1, then resume at 50 mg
                          daily on days 1 through 4 every 2 weeks (in
                          patients on the 50 mg dose) or at 50 mg daily
                          on days 1 through 7 every 2 weeks (in
                          patients on the 100 mg dose). If grade 3 or 4
                          hematologic toxicity recurs, discontinue
                          study drug permanently. For grade 3
                          nonhematologic toxicity: Hold study drug
                          until toxicity resolves to grade 1 or better,
                          then resume at reduced dose. For recurrent
                          grade 3 or any occurrence of grade 4
                          nonhematologic toxicity, discontinue study
                          drug permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Bristol-Myers Squibb
                          Company.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Etoposide/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       33419-42-0 (Etoposide)
LAST REVISION DATE        941207
ENTRY MONTH               9410
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 941123 ACTU:
                          6101.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 941102
                          ACTU: 0901.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 941101 ACTU: 2701.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 941004 ACTU:
                          2101.
NEW YORK                  St Clare's Hospital and Health Center 415
                          West 51st Street New York, NY 10019 Contact:
                          Phyllis Ristau (212) 459-8449 OPEN 941031
                          ACTU: 2204.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941116 ACTU: 1102.
 
17
UNIQUE IDENTIFIER         NIH/00681
PROTOCOL ID NUMBERS       NIAID ACTG 268
PROTOCOL TITLE            Gradual Initiation of
                          Trimethoprim/Sulfamethoxazole as Primary
                          Pneumocystis carinii Pneumonia Prophylaxis.
VERSION NUMBER & DATE     1 (941013)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Para MF
PROTOCOL CHAIRS           CO-CHAIR  Dohn MN, Frame P
GENERAL DESCRIPTION       PURPOSE: To determine whether gradual
                          initiation of trimethoprim/sulfamethoxazole
                          (TMP/SMX) reduces the incidence of
                          treatment-limiting adverse reactions compared
                          to the routine initiation of the drugs for
                          Pneumocystis carinii pneumonia (PCP)
                          prophylaxis in HIV-infected patients.
GENERAL DESCRIPTION       RATIONALE: Although a number of clinical
                          trials have demonstrated the superiority of
                          TMP/SMX for PCP prophylaxis, the incidence of
                          adverse reactions to this medication is high.
                          In a pilot study in which patients were
                          initiated with TMP/SMX prophylaxis by
                          gradually increasing the dose over 2 weeks,
                          no significant adverse reactions have
                          occurred.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either gradually increasing doses of
                          TMP/SMX suspension or routine daily
                          initiation of TMP/SMX double strength (DS)
                          tablets for 2 weeks. All patients will then
                          be switched over to receive open-label
                          TMP/SMX DS tablets daily for 10 weeks.
PROTOCOL PHASE            Phase IV
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA,
                          Western blot, HIV serum p24 antigen, or a
                          positive HIV culture. 2. CD4 count <= 250
                          cells/mm3 OR history or presence of thrush
                          regardless of CD4 count. 3. NO history of
                          confirmed or probable pneumocystosis.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 46,533
STUDY DESIGN              Randomized; Double-Blind; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 370 patients. (185
                          patients on each of two treatment arms)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 3/370 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count <= 250
                          cells/mm3 OR history or presence of thrush.
                          3. NO history of confirmed or probable
                          pneumocystosis. NOTE: Pregnant women are not
                          excluded, but safety issues should be
                          discussed with patient prior to enrollment.
                          NOTE: This study is appropriate for prisoner
                          participation. NOTE: Coenrollment in ongoing
                          ACTG antiretroviral studies is permitted
                          provided no new study drugs are added to the
                          patient's drug regimen for 4 weeks before or
                          after initiation of TMP/SMX. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.2 g/dl. (men); >= 8.5 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 250 cells/mm3. OR a
                          presence of thrush regardless of CD4 count. (
                          0 - 100 - 200 ).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not breast-feeding.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior aerosolized
                          pentamidine and dapsone for primary PCP
                          prophylaxis.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed if clinically
                          indicated: Recombinant erythropoietin (rEPO)
                          and G-CSF. Allowed for symptomatic treatment
                          of mild study drug toxicity: 1. Antipyretics
                          and analgesics (ibuprofen). 2. Antihistamines
                          (diphenhydramine HCl). 3. Terfenadine or
                          astemizole (but not allowed with concomitant
                          antifungal or macrolide use). 4. Systemic
                          steroids.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded at any time: Prior
                          TMP/SMX as primary PCP prophylaxis. Excluded
                          within 4 weeks prior to study entry: 1.
                          Initiation of antiretroviral agents. 2.
                          Initiation of anti-infective agents
                          (including TMP/SMX for another indication).
                          Excluded within 2 weeks prior to study entry:
                          1. Antihistamines. 2. Procysteine. 3.
                          Glutathione. 4. N-acetylcysteine (NAC). 5.
                          Systemic corticosteroids (unless used for
                          replacement purposes). 6. Leucovorin calcium.
                          7. TMP and sulfa drugs separately.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Procysteine. 2. Glutathione. 3.
                          N-acetylcysteine (NAC). 4. Antihistamines
                          (unless used for symptomatic treatment of
                          study drug toxicity). 5. Systemic
                          corticosteroids (unless used for replacement
                          purposes). 6. Leucovorin calcium (unless used
                          for symptomatic treatment of study drug
                          toxicity). 7. TMP or sulfa drugs outside of
                          the study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          adverse reactions to sulfa, trimethoprim, or
                          TMP/SMX. 2. Inability to comply with dosing
                          schedule or complete dosing record.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0030  Trimethoprim
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0031  Sulfamethoxazole
TRADE NAME OF SUBSTANCE   Drug 1 Septra (in combination with
                          sulfamethoxazole)
TRADE NAME OF SUBSTANCE   Drug 2 Septra (in combination with
                          trimethoprim)
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Arm I: 8, 16, 40,
                          80, and 160 mg in suspension daily given as
                          gradually increasing doses for 2 weeks (plus
                          tablet placebo), followed by 160 mg in tablet
                          daily for 10 weeks. Arm II: 160 mg in tablet
                          daily for 2 weeks (plus suspension
                          plafollowed by 160 mg in tablet daily for 10
                          weeks. Drug 2: Arm I: 40, 80, 200, 400, and
                          800 mg in suspension dailyas gradually
                          increasing doses for 2 weeks (plus tablet
                          placebo)followed by 800 mg in tablet daily
                          for 10 weeks. Arm II: 800 mg in tablet daily
                          for 2 weeks (plus suspension plafollowed by
                          800 mg in tablet daily for 10 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Tablet: 160 mg.
                          Suspension: 8, 16, 40, 80, and 160 mg. Drug
                          2: Tablet: 800 mg. Suspension: 40, 80, 200,
                          400, and 800 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 160 mg tablets
                          and 40 mg/5 ml suspension. Drug 2: Oral, 800
                          mg tablets and 200 mg/5 ml suspension
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 weeks.
OTHER TREATMENT INFO.     END POINT: Development of treatment-limiting
                          adverse effects.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Development of an intercurrent
                          illness such as major opportunistic
                          infection, new AIDS-defining illness,
                          generalized debilitation, or mental
                          incapacity that would preclude informed
                          consent. 3. Futher participation deemed
                          detrimental to patient's health or
                          well-being. 4. Patient noncompliance or
                          request of patient to withdraw from
                          treatment.
OTHER TREATMENT INFO.     MODIFICATION: No dose modification will be
                          allowed.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *PREVENTION & CONTROL
MESH HEADING              Trimethoprim-Sulfamethoxazole Combination/
                          *ADMINISTRATION & DOSAGE/ADVERSE EFFECTS
CAS REGISTRY NUMBER       8064-90-2 (Trimethoprim-Sulfamethoxazole
                          Combination)
LAST REVISION DATE        941207
ENTRY MONTH               9412
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 941123 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 941123 ACTU:
                          0202.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 941130 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 941130
                          ACTU: 2102.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941130 ACTU: 1102.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941123
                          ACTU: 2301.
 
18
UNIQUE IDENTIFIER         NIH/00627
PROTOCOL ID NUMBERS       NIAID ACTG 262
PROTOCOL TITLE            Methadone Effects on Zidovudine (AZT)
                          Disposition.
VERSION NUMBER & DATE     2 (940912)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Jatlow P
PROTOCOL CHAIRS           CO-CHAIR  Rainey P
GENERAL DESCRIPTION       PURPOSE: To determine whether methadone
                          maintenance alters the pharmacokinetics of
                          zidovudine (AZT). To determine whether any
                          such effect of methadone on disposition of
                          AZT is time dependent and whether a metabolic
                          interaction between AZT and methadone exists.
GENERAL DESCRIPTION       RATIONALE: Injection drug users represent an
                          increasing proportion of HIV-infected
                          persons. Since daily methadone maintenance is
                          the major chemical treatment for injection
                          drug abuse, it is important to determine the
                          impact of methadone on AZT absorption,
                          distribution, and elimination.
GENERAL DESCRIPTION       METHODOLOGY: After 6 days of inpatient
                          detoxification with clonidine, patients
                          addicted to opiates are randomized to receive
                          either oral or intravenous AZT for the first
                          dose, followed by determination of plasma and
                          urine pharmacokinetics. On the second day of
                          AZT dosing, the alternate form of
                          administration will be used for the first
                          dose. On both days, all other doses are given
                          orally. Patients then begin methadone
                          maintenance in combination with AZT for 7
                          days of inpatient treatment, with further
                          pharmacokinetic sampling. After
                          hospitalization for 16 days total, patients
                          continue AZT/methadone treatment on an
                          outpatient basis, and then 2 months later are
                          readmitted as inpatients for 5 days for
                          further pharmacokinetic sampling. Control
                          patients who are not addicted to opiates are
                          hospitalized for 3 days at study entry and
                          are randomized for AZT treatment and
                          pharmacokinetic sampling in the same manner
                          as the first group, although they will not
                          receive methadone treatment. Control patients
                          are readmitted for 2 days after 1 week of AZT
                          treatment and then again after 59 days of AZT
                          treatment.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           All patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot. 2. CD4 count 100 -
                          500 cells/mm3. 3. No active opportunistic
                          infection or wasting syndrome. Methadone
                          recipients only: Opiate addiction or previous
                          enrollment in a methadone treatment program
                          with eligibility for long-term methadone
                          maintenance and AZT therapy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 28,972
STUDY DESIGN              Controlled; Open Label; Pharmacokinetic; Drug
                          Combination
PROTOCOL DETAILS          STUDY INTENT: Combination and single
                          pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 15 patients. (10
                          methadone-treated patients; 5 control
                          patients)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately
                          65 days.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1/15 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count 100 - 500 cells/mm3. 3. No active
                          opportunistic infection or wasting syndrome.
                          4. Opiate addiction or prior enrollment in a
                          methadone treatment program (methadone
                          recipients only). 5. Admission to General
                          Clinical Research Center at Yale-New Haven
                          Hospital for clonidine detoxification
                          (methadone recipients only). [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 100 - 500 cells/mm3. (
                          100 - 200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 75 ml/min. /1.73 m2.
PATIENT INCLUSION CRIT.   OTHER: PT < 2 seconds above control. Serum
                          albumin > 2.5 g/dl; no ascites.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Continued active drug or
                          alcohol abuse or dependence that would
                          decrease the probability of study completion.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: 1. Rifampin or its
                          derivatives. 2. Phenytoin. 3. Barbiturates.
                          4. Cimetidine. 5. Other drugs known to induce
                          or inhibit hepatic microsomal enzymes.
                          Excluded within 14 days prior to study entry:
                          1. Any other experimental drug. 2. Drugs with
                          known nephrotoxic potential. Excluded within
                          72 hours prior to study entry: Amiodarone.
                          Anesthetics, general. Azithromycin.
                          Carbamazepine. Ciprofloxacin. Clarithromycin.
                          Dexamethasone. Disulfiram. Erythromycin.
                          Fluoroquinolones. Fluoxetine. Gestodene.
                          Hydrochlorothiazide. Hypoglycemics, oral.
                          Isoniazid. Itraconazole. Ketoconazole.
                          Levomepromazine. MAO inhibitors. Methoxsalen.
                          Nafcillin. Narcotic analgesics. Naringenin.
                          Norethindrone. Omeprazole. Pentazocine.
                          Phenothiazines. Quinidine. Ranitidine.
                          Rifabutin. Sedative Hypnotics.
                          Sulfaphenazole. Tranquilizers (except at
                          discretion of investigator and protocol
                          chair). Tricyclic antidepressants.
                          Troleandomycin. Warfarin.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Amiodarone.
                          Anesthetics, general. Azithromycin.
                          Barbiturates. Carbamazepine. Cimetidine.
                          Ciprofloxacin. Clarithromycin. Dexamethasone.
                          Disulfiram. Erythromycin. Fluoroquinolones.
                          Fluoxetine. Gestodene. Hydrochlorothiazide.
                          Hypoglycemics, oral. Isoniazid. Itraconazole.
                          Ketoconazole. Levomepromazine. MAO
                          inhibitors. Methoxsalen. Nafcillin. Narcotic
                          analgesics. Naringenin. Norethindrone.
                          Omeprazole. Pentazocine. Phenothiazines.
                          Phenytoin. Quinidine. Ranitidine. Rifabutin.
                          Rifampin. Sedative Hypnotics. Sulfaphenazole.
                          Tranquilizers (except at discretion of
                          investigator and protocol chair). Tricyclic
                          antidepressants. Troleandomycin. Warfarin.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Inadequate IV access. 2. Benzodiazepine
                          abuse.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0023  Methadone
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Kathryn Pattishall (919) 315-4440 Contact: Dr
                          Andy Sopchak (919) 315-3891.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Oral dose: 200 mg
                          thrice daily. IV dose: 150 mg over 30
                          minutes. Drug 2: 30 mg on day 3, 40 mg on day
                          4, and 50 mg on day 5 and thereafter. (Per
                          09/12/94 amendment, dose may be increased to
                          7during the outpatient portion of the study,
                          if indicated.)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Oral dose: 600 mg. IV
                          dose: 150 mg. Drug 2: 30, 40, or 50 mg, or,
                          per 09/12/94 amendment, 75 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules
                          or 20 ml vials. Drug 2: Oral, 10 mg/ml stock
                          solution
OTHER TREATMENT INFO.     TREATMENT DURATION: 59 days.
OTHER TREATMENT INFO.     END POINT: Pharmacokinetic profile.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Completion of
                          three sets of pharmacokinetic studies. 2.
                          Unacceptable toxicity. 3. Use of any
                          prohibited medications. 4. Decision of
                          patient to withdraw from study. 5. Positive
                          urine drug abuse screen or serum alchol test
                          that reveals drug abuse or decreases
                          likelihood of study completion by patient.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Interactions
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Methadone/*ADVERSE EFFECTS/PHARMACOKINETICS/
                          THERAPEUTIC USE
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/*PHARMACOKINETICS/THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       76-99-3 (Methadone)
LAST REVISION DATE        941207
ENTRY MONTH               9406
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 940524 ACTU: 6401.
 
19
UNIQUE IDENTIFIER         NIH/00645
PROTOCOL ID NUMBERS       NIAID ACTG 261
PROTOCOL TITLE            A Phase II Double-Blind Study of Delavirdine
                          Mesylate ( U-90152 ) in Combination With
                          Zidovudine (AZT) and/or Didanosine (ddI)
                          Versus AZT and ddI Combination Therapy.
VERSION NUMBER & DATE     (940718)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Friedland G
PROTOCOL CHAIRS           CO-CHAIR  Fischl MA, Pollard R
GENERAL DESCRIPTION       PURPOSE: To determine the safety and anti-HIV
                          activity of delavirdine mesylate (U-90152) in
                          combination with zidovudine (AZT) and/or
                          didanosine (ddI) versus AZT/ddI combination.
GENERAL DESCRIPTION       RATIONALE: U-90152 has demonstrated anti-HIV
                          activity. Since the combination of this drug
                          with either AZT or ddI has synergistic
                          inhibitory activity against HIV-1 in vitro,
                          and triple therapy appears to have greater
                          inhibitory activity against HIV-1 in vitro
                          than dual therapy, the use of U-90152 in
                          combination with AZT and/or ddI may improve
                          the benefits of these drugs in persons with
                          HIV disease.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive U-90152/AZT/ddI, U-90152/AZT,
                          U-90152/ddI, or AZT/ddI for 48 weeks.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot, HIV antigen, HIV
                          culture, or a second antibody test other than
                          ELISA. 2. CD4 count 100 - 500 cells/mm3
                          within 60 days prior to study entry. 3. Prior
                          cumulative monotherapy of <= 6 months (may
                          have taken either AZT or ddI, but not both)
                          OR no prior antiretroviral therapy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 45,914
STUDY DESIGN              Randomized; Multicenter; Double-Blind; 4-Arm;
                          Drug Combination; Comparative
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy, Comparative drug
                          therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 471 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 106/471 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 46 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count 100 -
                          500 cells/mm3. 3. Prior cumulative
                          monotherapy of <= 6 months (may have taken
                          either AZT or ddI, but not both) OR no prior
                          antiretroviral therapy. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.2 g/dl. (men); >= 8.9 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 100 - 500 cells/mm3. (
                          100 - 200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN. Or <= 5 x ULN if liver
                          function abnormalities have been stable for 1
                          yea
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN. Or <= 5 x ULN if liver
                          function abnormalities have been stable for 1
                          year.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min. (If
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3. Serum
                          amylase <= 1.5 x ULN (higher value permitted
                          if both fractionated pancreatic amylase and
                          lipase are < 1.5 x ULN).
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed for cutaneous
                          Kaposi's sarcoma: 1. Localized radiation
                          therapy. 2. Limited intralesional therapy.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: PCP
                          prophylaxis for patients with CD4 count <=
                          300 cells/mm3. Allowed: 1. Topical antifungal
                          agents. 2. Oral ketoconazole, fluconazole,
                          and itraconazole for candidiasis or
                          disseminated fungal infections. 3. Isoniazid,
                          ethambutol, pyrazinamide, clofazimine,
                          ciprofloxacin, and clarithromycin for acute
                          or maintenance therapy for mycobacterial
                          disease. 4. Acute or maintenance therapy for
                          toxoplasmosis. 5. Acute or maintenance
                          therapy with acyclovir (no more than 1000
                          mg/day) for herpes simplex virus infection.
                          6. rEPO and rG-CSF. 7. Antibiotics for
                          bacterial infections (except rifampin and
                          rifabutin). 8. Antipyretics, analgesics,
                          nonsteroidal anti-inflammatory agents,
                          antiemetics, and methadone.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of intolerance to AZT at <= 600
                          mg/day or ddI at <= 400 mg/day or
                          discontinuation of either drug for toxicity.
                          2. History of pancreatitis. 3. History of
                          grade 2 or worse peripheral neuropathy. 4.
                          Unexplained temperature >= 38.5 C on any 7
                          days within the past 30 days. 5. Chronic
                          diarrhea on any 15 days during the past 30
                          days. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug or alcohol use.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          foscarnet as induction or maintenance
                          therapy. 2. Prior U-90152. 3. Prior ddC or
                          d4T. 4. Prior AZT/ddI in combination or taken
                          separately at different times. 5. Prior
                          nonnucleoside reverse transcriptase
                          inhibitors (nevirapine, atevirdine, etc.). 6.
                          HIV-1 vaccine within the past 90 days. 7.
                          Acute treatment for a serious infection or
                          for any opportunistic infection within the
                          past 14 days. Excluded within the past 30
                          days: 1. Interferon or interleukin. 2.
                          Rifampin. 3. Rifabutin. 4. Terfenadine. 5.
                          Astemizole. 6. Loratadine. 7.
                          Trifluoperazine. 8. Piperazine. 9.
                          Recombinant EPO or G-CSF. 10. Any other
                          investigational drug.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral therapies and biologic
                          response modifiers (except for study
                          medications, rEPO, and rG-CSF). 2. Rifampin.
                          3. Rifabutin. 4. Terfenadine. 5. Astemizole.
                          6. Loratadine. 7. Trifluoperazine. 8.
                          Piperazine. 9. Systemic corticosteroids for
                          more than 21 consecutive days. 10. Foscarnet.
                          11. Systemic cytotoxic chemotherapy for a
                          malignancy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy (other than basal or squamous cell
                          carcinoma of the skin, Stage 1 or 2 cervical
                          intraepithelial neoplasia, or minimal
                          Kaposi's sarcoma). 2. Considered to be
                          unlikely to comply with study requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0166  U-90152
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
TRADE NAME OF SUBSTANCE   Drug 3 Videx
MANUFACTURERS             Drug 1: The Upjohn Company 7000 Portage Road
                          Kalamazoo, MI 49001 Contact: James VanSweden
                          (616) 323-4696.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 3: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 400 mg (or placebo)
                          TID for 48 weeks. Drug 2: 200 mg (or placebo)
                          TID for 48 weeks. Drug 3: 200 mg (or placebo)
                          BID for 48 weeks (125 mg or placeboin
                          patients weighing < 60 kg)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1200 mg. Drug 2: 600
                          mg. Drug 3: 400 mg (or 250 mg in patients
                          weighing < 60 kg)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg tablets.
                          Drug 2: Oral, 100 mg capsules. Drug 3: Oral;
                          25, 50, and 100 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Efficacy, toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Development of a malignancy or
                          progressive Kaposi's sarcoma requiring
                          systemic therapy or radiation therapy. 3.
                          Termination of study by the FDA, NIAID DAIDS,
                          ACTG or pharmaceutical sponsors. 4. Pregnancy
                          or breast-feeding.
OTHER TREATMENT INFO.     MODIFICATION: Dose interruptions,
                          modifications, and discontinuations will be
                          made for all grade 3 and 4 toxicities
                          considered to be related to study drugs.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Didanosine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9409
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 941114 ACTU: 5801.
CALIFORNIA                Olive View Medical Center / Department of
                          Medicine 14445 Olive View Drive / 2B182 Olive
                          View Medical Center Sylmar, CA 91342 Contact:
                          Betsy Manchester (818) 364-3205 OPEN 941012
                          ACTU: 0602.
CALIFORNIA                Veterans Admin Hospital at San Diego / UCSD
                          Med Center 9500 Gilman Drive / # 0672 La
                          Jolla, CA 92093 Contact: Candace McIvor (619)
                          534-7170 OPEN 941110 ACTU: 0702.
CALIFORNIA                University of California San Diego 9500
                          Gilman Drive / Clinical Sciences Bldg
                          LaJolla, CA 92093-0672 Contact: Candace
                          McIvor (619) 534-7170 OPEN 941110 ACTU: 0701.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840OPEN 940919 ACTU: 0801.
CALIFORNIA                Merrit-Peralta Medical Ctr/Adult Immunology
                          Clinic U of CA 450 30th Street Oakland, CA
                          94609 Contact: Bruce Ross (510) 273-8200
                          Contact: David Greenberg OPEN 940919 ACTU:
                          0804.
COLORADO                  Denver Department of Health and Hospitals /
                          Univ of CO Colorado ACTU / Campus Box B 163 /
                          4200 East Ninth Avenue Denver, CO 80262
                          Contact: M Graham Ray (303) 270-8551 OPEN
                          940921 ACTU: 6102.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941026 ACTU:
                          6104.
COLORADO                  Kaiser Permanente Franklin Med Cntr / Univ
                          Col Hlth Sci Cntr 4200 East Ninth Avenue /
                          Colorado ACTU / Campus Box B-163 Denver, CO
                          80262 Contact: Graham Ray (303) 270-8551
                          Contact: FAX (303) 270-6102 OPEN 940921 ACTU:
                          6103.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 941005 ACTU: 6401.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 940916
                          ACTU: 0901.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 940921
                          ACTU: 5201.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 941005 ACTU: 7201.
MASSACHUSETTS             Massachusetts General Hospital / Harvard 55
                          Fruit Street Gray 5 Boston, MA 02114 Contact:
                          Ellen Godfrey (617) 726-5598 OPEN 941020
                          ACTU: 0101.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02115 Contact: Sheila Hussey (617)
                          735-4103 OPEN 940913 ACTU: 0102.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 OPEN 941020 ACTU: 0104.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 941011 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 941116 ACTU:
                          0202.
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 941012 ACTU:
                          1501.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 941031 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 941031
                          ACTU: 2102.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 941027 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 941024 ACTU: 0401.
NEW YORK                  Memorial Hospital / Memorial Sloan-Kettering
                          Cancer Center 1275 York Avenue New York, NY
                          10021 Contact: Gloria Gilbert (212) 639-7169
                          OPEN 941201 ACTU: 2202.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          941024 ACTU: 2201.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          941017 ACTU: 1801.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 941110 ACTU: 7502.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 941205 ACTU: 1906.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 941114
                          ACTU: 1902.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 941205 ACTU: 1903.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forcheimer - ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 Contact: FAX (718) 597-5814 OPEN
                          941205 ACTU: 1909.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 941205
                          ACTU: 1904.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 941114 ACTU: 1901.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 941003
                          ACTU: 5901.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          941005 ACTU: 7403.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          941005 ACTU: 7402.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 941005 ACTU: 7401.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 940921 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941017 ACTU: 1102.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 941017 ACTU: 1101.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941003
                          ACTU: 2301.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 941003 ACTU: 2501.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 941017 ACTU:
                          2401.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 941014
                          ACTU: 5401.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 941103 ACTU: 6202.
 
20
UNIQUE IDENTIFIER         NIH/00662
PROTOCOL ID NUMBERS       NIAID ACTG 260
PROTOCOL TITLE            Randomized, Phase I/II, Dose-Ranging,
                          Open-Label Trial of the Anti-HIV Activity of
                          Delavirdine Mesylate (DLV; U-90152S).
VERSION NUMBER & DATE     1 (940908)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To study the safety and
                          tolerance of delavirdine mesylate (U-90152)
                          monotherapy. To compare the anti-HIV activity
                          of three blood concentration levels of this
                          agent with nucleoside analog monotherapy,
                          either zidovudince (AZT) or didanosine (ddI),
                          based on the reduction of HIV viral burden.
                          SECONDARY: To use pharmacokinetic parameters
                          to assess the relationship between daily drug
                          exposure and antiviral activity and toxicity
                          of the U-90152, AZT, and ddI monotherapy. To
                          assess anti-HIV activity using other disease
                          markers.
GENERAL DESCRIPTION       RATIONALE: Data suggest that
                          bisheteroarylpiperazines (BHAPs) such as
                          delavirdine mesylate are potent and safe
                          anti-HIV agents and may have different
                          biological behavior than other currently
                          available nonnucleoside RT inhibitors.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive U-90152 at one of three doses
                          (treatment arms I through III) or either AZT
                          or ddI (treatment arm IV). Patients on arm IV
                          who are AZT-naive receive AZT; those who are
                          AZT-experienced receive ddI. Treatment
                          continues for 24 weeks.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 infection by ELISA
                          confirmed by Western blot, HIV antigen, HIV
                          culture, or a second antibody test by a
                          method other than ELISA. 2. CD4 count 200 -
                          500 cells/mm3 within 45 days prior to study
                          entry. 3. Either no prior antiretroviral
                          therapy or discontinued AZT monotherapy 3 or
                          more weeks prior to study entry. NOTE: Half
                          of patients should be antiretroviral naive.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 45,914
STUDY DESIGN              Randomized; Multicenter; Open Label; 4-Arm;
                          Drug Tolerance; Dose Ranging;
                          Pharmacokinetic; Comparative
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy, Pharmacokinetics, Comparative
                          toxicity, Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 120 patients. (30 patients
                          on each of four treatment arms)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 36/120 (941207).
PROTOCOL DETAILS          STUDY DURATION: 24 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 9 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection. 2. CD4 count 200 -
                          500 cells/mm3. 3. Either no prior
                          antiretroviral therapy or discontinued AZT
                          monotherapy 3 or more weeks prior to study
                          entry. NOTE: Half of patients should be
                          antiretroviral naive. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.2 g/dl. (men); >= 8.9 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3.0 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 75 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3. Serum
                          amylase <= 1.5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior AZT.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. PCP
                          prophylaxis. 2. Topical antifungal agents,
                          clotrimazole troches, nystatin oral
                          suspension, topical ketoconazole, and oral
                          fluconazole. 3. Acyclovir (<= 1000 mg/day) as
                          maintenance therapy for herpes simplex virus.
                          4. Recombinant erythropoietin and G-CSF. 5.
                          Antibiotics for bacterial infections, unless
                          specifically excluded. 6. Symptomatic
                          treatment such as antipyretics, analgesics,
                          nonsteroidal anti-inflammatory agents, and
                          antiemetics. 7. Antacids.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of pancreatitis (in patients who
                          received prior AZT). 2. History of grade 2 or
                          worse peripheral neuropathy (in patients who
                          received prior AZT). 3. History of
                          hypersensitivity to BHAP compounds (e.g.,
                          trifluoperazine - Stelazine, piperazine
                          citrate - Antepar). [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse
                          interfering with compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 30 days
                          prior to study entry: 1. Any investigational
                          medication. 2. Interferon. 3. Interleukin. 4.
                          Rifabutin. 5. Rifampin. 6. Terfenadine. 7.
                          Astemizole. 8. Loratadine. 9.
                          Trifluoperazine. 10. Piperazine citrate.
                          Excluded at any time: 1. Prior ddI, ddC, d4T,
                          or 3TC. 2. Prior foscarnet. 3. Prior BHAP
                          compound or other nonnucleoside RT inhibitor.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Rifabutin. 2. Rifampin. 3. Terfenadine. 4.
                          Astemizole. 5. Loratadine. 6.
                          Trifluoperazine. 7. Piperazine citrate. 8.
                          Any acute or chronic therapy for CMV, MAC,
                          toxoplasmosis, or disseminated fungal
                          infection. 9. Non-study antiretroviral
                          therapies, interferons, biologic response
                          modifiers, and HIV vaccines. 10. Systemic
                          corticosteroids for more than 21 consecutive
                          days. 11. Foscarnet. 12. Systemic cytotoxic
                          chemotherapy for a malignancy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded:
                          Malignancy other than minimal Kaposi's
                          sarcoma.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0166  U-90152
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
TRADE NAME OF SUBSTANCE   Drug 3 Videx
MANUFACTURERS             Drug 1: The Upjohn Company 7000 Portage Road
                          Kalamazoo, MI 49001 Contact: James VanSweden
                          (616) 323-4696.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 3: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200, 300, or 400 mg
                          TID as starting dose, with target trough
                          levels of 3-10, 11-30, or 31-50 micromolars,
                          respectivelDrug 2: 200 mg TID for 24 weeks.
                          Drug 3: 200 mg BID (125 mg BID if < 60 kg
                          body weight) for 24
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 600, 900, or 1200 mg.
                          Drug 2: 600 mg. Drug 3: 400 mg (250 mg if <
                          60 kg body weight)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 50 and 100 mg
                          tablets. Drug 2: Oral, 100 mg capsules. Drug
                          3: Oral; 25, 50, and 100 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Toxicity, efficacy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Indication for
                          systemic cytotoxic therapy for a newly
                          diagnosed malignancy or progressive Kaposi's
                          sarcoma. 2. Further participation deemed
                          detrimental to patient's health or
                          well-being. 3. Development of intercurrent
                          illness such as a major opportunistic
                          infection or new AIDS-defining illness (other
                          than Kaposi's sarcoma) or generalized
                          debilitation or mental incapacity that would
                          preclude informed consent. 4. Pregnancy. 5.
                          Patient non-compliance or desire of patient
                          to withdraw from study.
OTHER TREATMENT INFO.     MODIFICATION: Dose is held or reduced for
                          specific toxicities.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/PHARMACOKINETICS/THERAPEUTIC
                          USE
MESH HEADING              Didanosine/*ADVERSE EFFECTS/PHARMACOKINETICS/
                          THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/*ADVERSE EFFECTS/PHARMACOKINETICS/
                          THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9410
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 941017
                          ACTU: 0501.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 941013 ACTU:
                          6101.
COLORADO                  Kaiser Permanente Franklin Med Cntr / Univ
                          Col Hlth Sci Cntr 4200 East Ninth Avenue /
                          Colorado ACTU / Campus Box B-163 Denver, CO
                          80262 Contact: Graham Ray (303) 270-8551
                          Contact: FAX (303) 270-6102 OPEN 941013 ACTU:
                          6103.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941031 ACTU:
                          6104.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 941021
                          ACTU: 0901.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 941123 ACTU: 2701.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 941115 ACTU: 1103.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 941031 ACTU: 1101.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941013
                          ACTU: 2301.
 
21
UNIQUE IDENTIFIER         NIH/00579
PROTOCOL ID NUMBERS       NIAID ACTG 259
PROTOCOL TITLE            A Phase II Double-Blind Study of Two Doses of
                          SC-49483 in Combination With Zidovudine (AZT)
                          Versus AZT.
VERSION NUMBER & DATE     2 (940719)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Fischl MA
PROTOCOL CHAIRS           CO-CHAIR  Saag M
GENERAL DESCRIPTION       PURPOSE: To determine the safety and anti-HIV
                          activity of two doses of SC-49483 in
                          combination with zidovudine (AZT) versus AZT
                          alone. To determine the influences of viral
                          phenotype on the anti-HIV activity of these
                          treatment regimens.
GENERAL DESCRIPTION       RATIONALE: SC-49483 has no inherent activity
                          against HIV-1 but is converted in the
                          intestinal wall to SC-48334, which has
                          demonstrated anti-HIV activity. Since
                          SC-49483 causes significantly less
                          gastrointestinal toxicity than SC-48334, the
                          combination of SC-49483 with AZT may improve
                          the benefits of both drugs in patients with
                          HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive AZT alone or in combination with one
                          of two doses of SC-49483, administered three
                          times daily. Treatment continues for 16 to 24
                          weeks. Per 07/19/94 amendment: At the end of
                          24 weeks, blinded treatment continues for an
                          additional 4 weeks, at which time patients
                          may receive open-label drug on an optional
                          basis for 90 days.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA confirmed by Western blot, HIV antigen,
                          HIV culture, or a second antibody test by a
                          method other than ELISA. 2. Per 07/19/94
                          amendment, one of the following: - CD4 count
                          150 - 350 cells/mm3 within 60 days prior to
                          study entry AND prior AZT for no more than 12
                          months cumulative (given with or without ddI
                          or ddC). - CD4 count 50 - 350 cells/mm3
                          within 60 days prior to study entry AND no
                          prior antiretroviral therapy. 3. MT-2 cell
                          assay (to determine synctial vs. nonsynctial
                          viral phenotype) within 60 days prior to
                          study entry. NOTE: Minimal Kaposi's sarcoma
                          is permitted.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 44,154
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          3-Arm; Dose Comparison; Drug Tolerance;
                          Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination and single drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 210 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 16 - 24 weeks.
                          Per amendment, possibly extended for 118 days
                          after the 24th week.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 164/210 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 37 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. Per
                          07/19/94 amendment, one of the following: -
                          CD4 count 150 - 350 cells/mm3 within 60 days
                          prior to study entry AND prior AZT for no
                          more than 12 months cumulative (given with or
                          without ddI or ddC). - CD4 count 50 - 350
                          cells/mm3 within 60 days prior to study entry
                          AND no prior antiretroviral therapy. 3. MT-2
                          cell assay within 60 days prior to study
                          entry. NOTE: Minimal Kaposi's sarcoma is
                          permitted. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.2 g/dl. (men); >= 8.9 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 50 - 350 cells/mm3. (if
                          no prior antiretroviral therapy). OR 150 -
                          350 cells/mm3 (if prior antiretroviral
                          therapy). ( 100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3.0 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control /contraception during
                          the study and for 60 days after.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Localized
                          radiation therapy and limited intralesional
                          therapy for cutaneous Kaposi's sarcoma.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: PCP
                          prophylaxis (trimethoprim/sulfamethoxazole,
                          dapsone, or aerosolized pentamidine) in
                          patients with CD4 count <= 200 cells/mm3.
                          Allowed: 1. Topical antifungal agents,
                          ketoconazole, fluconazole, and itraconazole
                          for candidiasis or disseminated fungal
                          infections, as medically indicated. 2.
                          Maintenance therapy for Mycobacteria disease
                          with isoniazid, ethambutol, rifampin,
                          pyrazinamide, clofazimine, ciprofloxacin,
                          clarithromycin, or rifabutin. 3. Maintenance
                          therapy for toxoplasmosis with pyrimethamine,
                          sulfadiazine, or clindamycin. 4. Maintenance
                          therapy for herpes simplex virus with
                          acyclovir at <= 1000 mg/day. 5. Recombinant
                          erythropoietin and G-CSF, if indicated. 6.
                          Antibiotics for bacterial infections. 7.
                          Symptomatic treatment such as antipyretics,
                          analgesics, nonsteroidal anti-inflammatory
                          agents, and antiemetics.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of cataracts. 2. History of
                          intolerance to AZT at <= 600 mg/day. 3.
                          Unexplained temperature >= 38.5 degrees C
                          that persists for any 7 days within the 30
                          days prior to study entry. 4. Chronic
                          diarrhea (defined as >= 3 stools per day)
                          that persists for any 15 days within the 30
                          days prior to study entry. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 60 days after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than 6
                          months (more than 12 months per 07/19/94
                          amendment) cumulative prior therapy with AZT.
                          2. Prior induction or maintenance therapy
                          with foscarnet. 3. Any investigational drug
                          within 30 days prior to study entry. 4. Prior
                          SC-49483 or SC-48334. 5. Prior ddC, ddI, or
                          stavudine (d4T) as monotherapy. 6. Interferon
                          or interleukin within 30 days prior to study
                          entry. 7. Prior nonnucleoside reverse
                          transcriptase inhibitors (e.g., NVP, ATV). 8.
                          Systemic corticosteroids for > 21 consecutive
                          days. 9. Acute treatment for a serious
                          infection or any opportunistic infection
                          within 14 days prior to study entry. 10.
                          Prior combination therapy with AZT, ddI,
                          and/or ddC within 30 days prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral therapies (other than study
                          drug). 2. Biologic response modifiers. 3.
                          Systemic corticosteroids for > 21 consecutive
                          days. 4. Foscarnet. 5. Systemic cytotoxic
                          chemotherapy for a malignancy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          condition are excluded: Malignancy other than
                          minimal Kaposi's sarcoma.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0193  SC-49483
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle Park, NC 27709
                          Contact: Mary Maha Elkins (919) 248-3294.
MANUFACTURERS             Drug 2: G D Searle & Company 4901 Searle
                          Parkway Skokie, IL 60077 Contact: Susan Smith
                          (708) 982-8975.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg TID for 16-24
                          weeks. Drug 2: 3 or 5 g (or placebo) TID,
                          with food, for 16-24 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 9 or 15
                          g
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules.
                          Drug 2: Oral, 1 g capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 16 to 24 weeks. Per
                          amendment, possibly extended for 118 days
                          beyond week 24.
OTHER TREATMENT INFO.     END POINT: Quantitative PBMC HIV-1
                          microculture titer, changes in plasma HIV RNA
                          by PCR, change in CD4 count, toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Dose-limiting
                          toxicity. 2. Development of malignancy or
                          progressive Kaposi's sarcoma that requires
                          systemic therapy or radiation therapy. 3.
                          Pregnancy. 4. Decision of the patient to
                          withdraw from study.
OTHER TREATMENT INFO.     MODIFICATION: Dose is held or reduced for
                          grade 3 or worse toxicities related to study
                          drug.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Burroughs Wellcome, G D
                          Searle & Company.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        941207
ENTRY MONTH               9402
ALABAMA                   University of Alabama at Birmingham 933 19th
                          Street S/1917 Research Clinic Room 219
                          Birmingham, AL 35294-2041 Contact: Robin
                          Noles (205) 934-7349 OPEN 940228.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          940311 ACTU: 1201.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840OPEN 940228 ACTU: 0801.
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 940610 ACTU: 0808.
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          940311 ACTU: 0802.
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 941123
                          ACTU: 0501.
CALIFORNIA                Merrit-Peralta Medical Ctr/Adult Immunology
                          Clinic U of CA 450 30th Street Oakland, CA
                          94609 Contact: Bruce Ross (510) 273-8200
                          Contact: David Greenberg OPEN 940228 ACTU:
                          0804.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 941115 ACTU:
                          6101.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 940413 ACTU: 6401.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 940330 ACTU: 5701.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 940207
                          ACTU: 0901.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940207 ACTU: 2701.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941017 ACTU: 2708.
ILLINOIS                  Illinois Masonic Med Ctr / Northwestern Univ
                          Med Schl Passavant Pavilion Room 823 / 303
                          East Superior Chicago, IL 60611 Contact:
                          Baiba L Berzins (312) 908-9636 OPEN 941024
                          ACTU: 2707.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940228 ACTU: 2702.
ILLINOIS                  Cook County Hospital Passavant Pavilion /
                          Room 823 / 303 East Superior Chicago, IL
                          60611 Contact: Baiba L Berzins (312) 908-9636
                          OPEN 940422 ACTU: 2705.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940214 ACTU: 2601.
INDIANA                   Methodist Hospital Of Indiana 550 North
                          University Boulevard Room 5550 Indianapolis,
                          IN 46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940228 ACTU: 2602.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940208 ACTU:
                          2101.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          940503 ACTU: 3201.
NORTH CAROLINA            Wake County Department of Health Hosp South
                          Room 0207 Box 3284 Durham, NC 27710 Contact:
                          Kelley Rayle (919) 250-1035 OPEN 940502 ACTU:
                          3206.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 940228 ACTU:
                          1802.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940224 ACTU: 1801.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 940311 ACTU: 7501.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 940422 ACTU: 7502.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 940207 ACTU:
                          1905.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940207 ACTU: 1906.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940210
                          ACTU: 1902.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940210
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940210
                          ACTU: 1904.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940210 ACTU: 1901.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940210 ACTU: 1903.
NEW YORK                  North Central Bronx Hospital / Samaritan
                          Village Inc 418 Forchheimer ID / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940207 ACTU: 1907.
NEW YORK                  City Hospital at Elmhurst / Mt Sinai 79-01
                          Broadway Room D1-29 Elmhurst, NY 11373
                          Contact: Dinah Reitman (718) 334-3963 OPEN
                          940323 ACTU: 1803.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941110 ACTU: 1102.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 940311 ACTU:
                          2401.
 
22
UNIQUE IDENTIFIER         NIH/00634
PROTOCOL ID NUMBERS       NIAID ACTG 252
PROTOCOL TITLE            Phase II Trial of Sequential Chemotherapy and
                          Radiotherapy for AIDS-Related Primary Central
                          Nervous System Lymphoma.
VERSION NUMBER & DATE     (940517)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Krigel RL
PROTOCOL CHAIRS           CO-CHAIR  Von Roenn J
GENERAL DESCRIPTION       PURPOSE: To estimate the response rate,
                          overall and disease-free survival,
                          toxicities, factors associated with outcome,
                          and effect on quality of life in patients
                          with AIDS-related primary CNS lymphoma
                          treated with CHOD (cyclophosphamide,
                          doxorubicin, vincristine, and dexamethasone)
                          plus granulocyte-colony stimulating factor
                          (G-CSF) and external beam irradiation. To
                          determine other clinical markers present in
                          this patient population.
GENERAL DESCRIPTION       RATIONALE: Combined modality therapy may
                          prove of benefit for patients with
                          AIDS-related primary CNS lymphoma.
GENERAL DESCRIPTION       METHODOLOGY: Patients who upon staging workup
                          are found to be without systemic involvement
                          undergo one cycle of chemotherapy with
                          cyclophosphamide, doxorubicin, vincristine,
                          dexamethasone, and G-CSF. Cyclophosphamide,
                          doxorubicin, and vincristine are administered
                          intravenously on day 1. Dexamethasone is
                          administered intravenously on day 1 and then
                          orally thereafter with gradual
                          discontinuation. G-CSF is administered
                          subcutaneously daily beginning on day 2 and
                          continuing for a total of 10 days or until
                          blood counts have recovered to an acceptable
                          level. Patients with evidence of cancer cells
                          in their cerebrospinal fluid (CSF) will
                          receive chemotherapy with intrathecal
                          cytarabine twice weekly until no further
                          evidence of cancer cells is found in the CSF,
                          then once weekly for 6 weeks, and then
                          monthly for 10 months. Seven to ten days
                          following completion of one cycle of
                          chemotherapy, patients undergo radiotherapy
                          to the brain at a dose of 2.5 Gy daily for 5
                          days per week for approximately 4 weeks.
                          Total dose to the whole brain and meninges is
                          30.0 Gy in 12 fractions, and total dose to
                          the primary boost volume is 10.0 Gy in 4
                          fractions. During therapy, blood is drawn
                          weekly and brain scans are performed every
                          3-12 weeks. An initial CSF sample will be
                          obtained by lumbar puncture.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (941207)
DISEASE STUDIED           Lymphoma, primary CNS.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive confirmed by
                          Western blot. 2. Biopsy proven primary CNS
                          non-Hodgkin's lymphoma, intermediate or high
                          grade histology involving the parenchyma of
                          the brain. 3. No prior cranial radiotherapy
                          or chemotherapy unless given for Kaposi's
                          sarcoma (cranial radiotherapy to other sites
                          is acceptable). 4. Intracranial
                          space-occupying lesion as documented by
                          preoperative CT-head or MRI. 5. No prior
                          history of lymphoma. 6. No clinical evidence
                          of systemic (extracranial) lymphoma
                          (documented by abdominal and chest CT scan
                          and bilateral bone marrow biopsy. 7. No more
                          than 3 weeks post-surgery. NOTE: Patients
                          entering treatment must undergo a lumbar
                          puncture with evaluation of CSF, unless
                          contraindicated.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    ECOG E 1493
STUDY DESIGN              Drug Combination; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug tolerance,
                          Combination drug therapy, Combination
                          modality therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 10
                          months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Primary CNS
                          lymphoma with NO systemic involvement. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3.0 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 3.0 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: 0 - 3 (ECOG).
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3.
PATIENT AGE               AGE: 16 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior
                          corticosteroids.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: 1. PCP
                          prophylaxis with Bactrim, dapsone, or
                          aerosolized pentamidine. 2. Oral candidiasis
                          prophylaxis with fluconazole, ketoconazole,
                          or clotrimazole oral troches. 3.
                          Antiretroviral agent available by therapy
                          IND. 4. MAI prophylaxis with rifabutin (in
                          patients with CD4 counts < 100 cells/mm3).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          No prior malignancy other than Kaposi's
                          sarcoma, curatively treated carcinoma in situ
                          of the cervix, or squamous cell or basal cell
                          carcinoma of the skin. 2. No new infectious
                          complications within the past 2 weeks that
                          require a change in antibiotics. 3. History
                          of myocardial infarction within the past 3
                          months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 15 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Prior
                          chemotherapy other than for Kaposi's sarcoma.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Any
                          investigational agent other than
                          antiretroviral agents available by therapy
                          IND.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Concomitant malignancy other than Kaposi's
                          sarcoma, curatively treated carcinoma in situ
                          of the cervix, or squamous or basal cell
                          carcinoma of the skin. 2. Active uncontrolled
                          infection. 3. Renal failure, active
                          nonmalignant duodenal ulcer, uncontrolled
                          diabetes mellitus, or other serious medical
                          conditions that would preclude aggressive
                          cytotoxic chemotherapy administration. 4.
                          Active heart disease (congestive heart
                          failure or heart block greater than first
                          degree on EKG).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0048  Cyclophosphamide
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0047  Doxorubicin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0046  Vincristine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0013  Dexamethasone
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0086  Granulocyte
                          colony-stimulating factor
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0038  Cytarabine
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Merck and Company Incorporated
                          Professional Services West Point, PA 19486
                          Contact: Professional Information (215)
                          661-7300 Contact: Prof Info / Call Collect
                          (215) 652-3298.
MANUFACTURERS             Drug 5: Amgen Incorporated 1840 DeHavilland
                          Drive Thousand Oaks, CA 91320-1789 Contact:
                          Mark Davis (805) 499-5725 X 4142.
MANUFACTURERS             Drug 6: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 750 mg/m2 on day 1.
                          Drug 2: 50 mg/m2 on day 1. Drug 3: 1.4 mg/m2
                          (maximum 2.0 mg) on day 1. Drug 4: 16 mg IV
                          on day 1, then 16 mg PO or IV daily, with
                          tapeas tolerated. (Dexamethasone is
                          physically incompatible with doxorubicin.).
                          Drug 5: 5 mcg/kg daily beginning on day 2 for
                          a minimum of 10 dand until granulocytes are >
                          500 cells/mm3 for 2 days. Drug 6: 50 mg via
                          lumbar puncture or Ommaya reservoir,
                          administtwice daily until CSF is negative,
                          then weekly for 6 weeks, themonthly for 10
                          months (administered only in patients with
                          positCSF cytology)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 4: 16 mg. Drug 5: 5 mcg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV). Drug
                          2: Intravenous (IV). Drug 3: Intravenous
                          (IV). Drug 4: Intravenous (IV) and Oral. Drug
                          5: Subcutaneous. Drug 6: Intrathecal
OTHER TREATMENT INFO.     END POINT: Response rate, survival, toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Disease
                          progression.
OTHER TREATMENT INFO.     MODIFICATION: For bilirubin 2.0 - 3.0 mg/dl:
                          Reduce vincristine and doxorubicin doses by
                          50 percent. For unacceptable corticosteroid
                          toxicity: Modify or discontinue dexamethasone
                          dose at the discretion of the investigator.
                          For grade 3 major organ toxicity: Reduce
                          G-CSF dose by 50 percent. If grade 3 toxicity
                          persists for 7 days or advances to grade 4
                          toxicity, discontinue G-CSF permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents, Combined/*THERAPEUTIC
                          USE
MESH HEADING              Brain Neoplasms/*DRUG THERAPY/RADIOTHERAPY
MESH HEADING              Combined Modality Therapy
MESH HEADING              Cyclophosphamide/THERAPEUTIC USE
MESH HEADING              Cytarabine/THERAPEUTIC USE
MESH HEADING              Dexamethasone/THERAPEUTIC USE
MESH HEADING              Doxorubicin/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Granulocyte Colony-Stimulating Factor/
                          THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Lymphoma, High-Grade/*DRUG THERAPY/
                          RADIOTHERAPY
MESH HEADING              Lymphoma, Intermediate-Grade/*DRUG THERAPY/
                          RADIOTHERAPY
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Vincristine/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antineoplastic Agents, Combined)
CAS REGISTRY NUMBER       147-94-4 (Cytarabine)
CAS REGISTRY NUMBER       23214-92-8 (Doxorubicin)
CAS REGISTRY NUMBER       50-02-2 (Dexamethasone)
CAS REGISTRY NUMBER       50-18-0 (Cyclophosphamide)
CAS REGISTRY NUMBER       57-22-7 (Vincristine)
CAS REGISTRY NUMBER       62683-29-8 (Granulocyte Colony-Stimulating
                          Factor)
LAST REVISION DATE        941207
ENTRY MONTH               9406
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 940927 ACTU:
                          6101.
MASSACHUSETTS             ECOG Data Management Office 303 Boylston
                          Street Brookline, MA 02146 Contact:
                          Unspecified (PHYSICIANS ONLY) (617) 632-3610
                          OPEN / USA accrual 940602.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940912 ACTU:
                          2101.
 
23
UNIQUE IDENTIFIER         NIH/00572
PROTOCOL ID NUMBERS       NIAID ACTG 251
PROTOCOL TITLE            Thalidomide for Treatment of Oral and
                          Esophageal Aphthous Ulcers and HIV Viremia in
                          Patients With HIV Infection.
VERSION NUMBER & DATE     4 (940829)
PROTOCOL CHAIRS           CHAIR  Jacobson JM
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To evaluate the
                          effectiveness and safety of thalidomide for
                          treatment of oral and esophageal aphthous
                          ulcers (those unrelated to a known infection
                          or malignancy) in patients with advanced HIV
                          disease. To evaluate the effect of
                          thalidomide on HIV load in this patient
                          population. Per 06/28/94 amendment, to
                          evaluate the effectiveness of thalidomide in
                          preventing recurrences in patients whose
                          aphthae completely heal at the end of acute
                          treatment. SECONDARY: To evaluate the effect
                          of thalidomide on blood tumor necrosis factor
                          (TNF) levels and to obtain pharmacokinetic
                          data on the drug. Per 06/28/94 amendment, to
                          evaluate the safety of thalidomide.
GENERAL DESCRIPTION       RATIONALE: Aphthous ulcers of the mouth or
                          esophagus can interfere with eating,
                          resulting in malnutrition and wasting.
                          Thalidomide has been proposed as an effective
                          therapy for severe forms of aphthous
                          ulceration in AIDS patients.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive 4 weeks of either 200 mg thalidomide
                          or placebo orally, administered once daily.
                          Patients are followed weekly. Complete
                          responders after 4 weeks of acute treatment
                          enter a 24-week maintenance phase. A
                          pharmacokinetic substudy will be included.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Aphthous ulcers of mouth or esophagus.
DISEASES STATUS           Patients have the following symptoms and
                          conditions (Per amendment, patients initially
                          enter an acute treatment phase; those who
                          achieve complete response of aphthous healing
                          enter a maintenance phase): ACUTE TREATMENT
                          PHASE: 1. HIV infection documented by HIV
                          antibody, HIV p24 antigen, or isolation of
                          HIV in culture OR AIDS as defined by an
                          AIDS-defining opportunistic infection
                          confirmed by histology or culture. 2.
                          Biopsy-confirmed aphthous ulceration of the
                          mouth or esophagus lasting at least 2 weeks.
                          Biopsy should be performed within 8 weeks
                          prior to study entry and indicate no evidence
                          of a recognizable viral or fungal infection.
                          3. Negative culture of ulcer for Herpes
                          simplex within 8 weeks prior to study entry.
                          4. En face diameter of >= 5 mm for largest
                          aphthous ulcer. MAINTENANCE PHASE: Complete
                          response of oral and/or esophageal aphthae.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 43,791
STUDY DESIGN              Multicenter; Double-Blind; Randomized;
                          Placebo-Controlled; 2-Arm; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 164 patients. (80 patients
                          per treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 4
                          weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 20/164 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 30 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection or AIDS. 2.
                          Biopsy-confirmed aphthous ulceration of the
                          mouth or esophagus lasting at least 2 weeks.
                          3. Negative culture of ulcer for Herpes
                          simplex. 4. En face diameter of >= 5 mm for
                          largest aphthous ulcer. 5. Life expectancy of
                          at least 3 months. NOTE: This study is
                          approved for prisoner participation. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 5 x ULN.
                          Absolute neutrophils > 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 3 days prior to study
                          entry. Abstinence or effective method of
                          birth control / contraception during the
                          study and for 30 days after. Breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Anti-HIV
                          therapy provided therapy has remained
                          constant in the 4 weeks prior to study entry.
                          2. Narcotic analgesia after the first week of
                          treatment ONLY IF the patient is not
                          experiencing somnolence.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of grade 2 or worse bilateral
                          peripheral neuropathy. 2. Change in anti-HIV
                          therapy within 4 weeks prior to study entry.
                          3. Prior enrollment in ACTG 251 or prior
                          treatment of aphthous ulcers with
                          thalidomide. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 3 days prior to study
                          entry. No abstinence or no agreement to use
                          effective method of birth control during
                          study and for 30 days after. Not
                          breast-feeding.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation to
                          head and/or neck.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Systemic
                          and/or oral topical corticosteroids within 2
                          weeks prior to study entry. 2. Other putative
                          immunomodulators within 2 weeks prior to
                          study entry. 3. Prior thalidomide for
                          aphthous ulcers.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Acute
                          therapy for opportunistic infection. 2. ddC.
                          3. Pentoxifylline. 4. Methotrexate,
                          trimetrexate, alkylating agents. 5. Other
                          putative immunomodulators. 6. CNS depressants
                          and/or medications with sedative or hypnotic
                          effect. 7. Systemic and/or oral topical
                          corticosteroids. 8. Systemic chemotherapy for
                          Kaposi's sarcoma or other malignancies. 9.
                          Compounded antibacterial mouthwashes
                          containing anti-infective agents (such as
                          doxycycline, minocycline, tetracycline, or
                          nystatin).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          allergy to thalidomide. 2. Grade 2 or worse
                          bilateral peripheral neuropathy. EXCLUDED FOR
                          MAINTENANCE PHASE: Toxicity other than
                          somnolence in acute phase that required
                          discontinuation of drug.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0184  Thalidomide
MANUFACTURERS             Drug 1: Andrulis Pharmaceuticals Corporation
                          11800 Baltimore Avenue Beltsville, MD 20705
                          Contact: Dr Peter Andrulis (301) 419-2400.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Acute treatment
                          phase: 200 mg (or placebo) daily at bedtime
                          for 4 weeks. Maintenance phase: 100 mg (or
                          placebo) thrice weekly for 24 we
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Acute treatment phase:
                          200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 weeks.
OTHER TREATMENT INFO.     END POINT: Acute phase: Resolution of
                          aphthous ulcers, p24 antigen levels,
                          toxicity, pharmacokinetic profile.
                          Maintenance phase: Recurrence of aphthous
                          ulcers.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Dose-limiting
                          toxicity. 2. Pregnancy or unwillingness to
                          practice contraception. 3. Patient
                          noncompliance or desire to withdraw from
                          study.
OTHER TREATMENT INFO.     MODIFICATION: For somnolence persisting at
                          least 72 hours: Reduce daily dose by 50
                          percent. If somnolence persists for another
                          72 hours, then administer 50 percent dose
                          every other day. If somnolence persists
                          despite second dose reduction, then
                          discontiue drug permanently. For grade 2 or
                          worse peripheral neuropathy: Hold study drug
                          until toxicity resolves to grade 1 or better.
                          If toxicity resolves within 28 days, then
                          resume drug at 50 percent of daily dose. If
                          toxicity persists after 28 days of holding
                          drug and ulcer has not completely healed, or
                          if toxicity recurs on the reduced dose, then
                          discontinue drug permanently. For other grade
                          3 toxicities: Hold study drug until toxicity
                          resolves to grade 2 or better, then resume at
                          full dose. If grade 3 toxicity recurs, hold
                          study drug until toxicity resolves to grade 2
                          or better, then resume at 50 percent of daily
                          dose.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Andrulis Pharmaceuticals
                          Corporation.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Stomatitis, Aphthous/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Thalidomide/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       50-35-1 (Thalidomide)
LAST REVISION DATE        941207
ENTRY MONTH               9403
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          940606 ACTU: 1201.
CALIFORNIA                Harbor General / REI Lab / UCLA 1124 West
                          Carson Street Torrance, CA 90502 Contact:
                          Sally Kruger (310) 222-3848 Contact: Rick
                          Johnson OPEN 940308 ACTU: 0603.
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          940308 ACTU: 0802.
CALIFORNIA                Kaiser Permanente Medical Group / Stanford
                          University 2590 Geary Boulevard San
                          Francisco, CA 94115 Contact: Gretchen Van
                          Raalte (415) 202-3482 OPEN 941116 ACTU: 0502.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 940308 ACTU:
                          6101.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 940902
                          ACTU: 5201.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940303 ACTU: 2701.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940317 ACTU: 2702.
ILLINOIS                  Illinois Masonic Med Ctr / Northwestern Univ
                          Med Schl Passavant Pavilion Room 823 / 303
                          East Superior Chicago, IL 60611 Contact:
                          Baiba L Berzins (312) 908-9636 OPEN 941101
                          ACTU: 2707.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941205 ACTU: 2708.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940711 ACTU: 2601.
MASSACHUSETTS             Massachusetts General Hospital / Harvard 55
                          Fruit Street Gray 5 Boston, MA 02114 Contact:
                          Ellen Godfrey (617) 726-5598 OPEN 941024
                          ACTU: 0101.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          941017 ACTU: 3201.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 940616 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 940317 ACTU: 0401.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940308 ACTU: 1801.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940308 ACTU:
                          4301.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 940323 ACTU:
                          1905.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940323 ACTU: 1906.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940323 ACTU: 1903.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940323
                          ACTU: 1904.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940303 ACTU: 1901.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940303
                          ACTU: 1902.
NEW YORK                  Bronx Veterans Administration Medical Center
                          130 West Kingsbridge Road Bronx, NY 10468
                          Contact: Nancy Ostrow (718) 584-9000 X
                          667Contact: (718) 584-9000 X 667OPEN 940308
                          ACTU: 1804.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 941024 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          940609 ACTU: 1102.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940308 ACTU: 2501.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 940504
                          ACTU: 5401.
 
24
UNIQUE IDENTIFIER         NIH/00658
PROTOCOL ID NUMBERS       NIAID ACTG 250
PROTOCOL TITLE            A Phase I Study of Safety and
                          Pharmacokinetics of Nevirapine in HIV-1
                          Infected Pregnant Women and Neonates Born to
                          HIV-1 Infected Mothers.
VERSION NUMBER & DATE     1 (940902)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Pregnancy
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Sullivan JL
PROTOCOL CHAIRS           CO-CHAIR  Sperling R
GENERAL DESCRIPTION       PURPOSE: To determine the bioavailability,
                          pharmacokinetics, and short-term safety and
                          tolerance of nevirapine in HIV-1 infected
                          pregnant women and their newborns when
                          nevirapine is given to the mother during
                          active labor, and when their neonates are
                          dosed during the first week of life. To
                          determine the short-term safety profile of
                          mothers receiving zidovudine (AZT) who
                          received nevirapine during active labor, and
                          their neonates who received no dose, a single
                          dose, or multiple doses of nevirapine and who
                          are receiving AZT during the first 6 weeks of
                          life.
GENERAL DESCRIPTION       RATIONALE: Treatment of HIV-1 infected
                          pregnant women during active labor may result
                          in therapeutic levels of nevirapine in the
                          neonate at the time of exposure to HIV-1
                          during parturition, decreasing the neonate's
                          risk of infection.
GENERAL DESCRIPTION       METHODOLOGY: Pregnant women in active labor
                          receive single doses of oral nevirapine. The
                          neonates of the first four mothers receive no
                          drug, while the neonates of the second
                          four-patient cohort receive a single dose of
                          nevirapine. If neonatal antiviral levels of
                          nevirapine are not sustained for 7 days after
                          the single dose, a third cohort of pregnant
                          women will receive a single dose of
                          nevirapine and their neonates will receive
                          multiple doses of nevirapine to maintain an
                          antiviral effect for 7 days.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           MOTHERS have the following symptoms and
                          conditions: 1. HIV infection by two ELISAs
                          confirmed by an appropriate test (e.g.,
                          Western blot) or by a positive HIV culture
                          (blood or CSF). Historical data may be used.
                          2. Estimated gestational age >= 34 weeks. 3.
                          NO active opportunistic infection at study
                          entry. NEONATES must meet the following
                          criterion: Born to enrolled HIV-1 infected
                          women who have received study drug.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 42,003
STUDY DESIGN              Drug Tolerance; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 36 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 6-8 weeks
                          post-partum (mother); 6 mos. post-delivery
                          (baby)
PROTOCOL DETAILS          ACTUAL ACCRUAL: 4/36 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: MOTHERS must
                          have: 1. HIV infection. 2. Estimated
                          gestational age >= 34 weeks. 3. No active
                          opportunistic infection at study entry.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT AGE               AGE: 13 Years - 60 Years.
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Pregnant at term and
                          either in or beginning active labor as
                          defined by uterine contractions.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Phototherapy
                          (neonates).
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. AZT
                          (mothers and neonates). 2. Oral asthma
                          inhalers (mothers).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   SEX: MALE
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant at term
                          and not in or beginning active labor.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current use of illicit
                          substances and/or active chronic alcohol use.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Prior nevirapine.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          antiretroviral other than AZT. 2.
                          Corticosteroids (other than oral asthma
                          inhalers). 3. Anticoagulants. 4. Any
                          clavulinic acid-containing formulation (e.g.,
                          Augmentin, Timentin). 5. Benzodiazepines
                          other than study drug. 6. Phenobarbital. 7.
                          Barbiturates. 8. Antacids. 9. Magnesium
                          sulfate.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: MOTHERS with the following
                          symptoms or conditions are excluded: 1.
                          Intrauterine growth retardation. 2. Fetal
                          anomaly incompatible with life as determined
                          by pre-entry ultrasound. 3. Participation
                          during current pregnancy in any other
                          therapeutic or vaccine perinatal trial. 4.
                          Known hypersensitivity to any benzodiazepine.
                          5. Serious bacterial infection.
PATIENT EXCLUSION CRIT.   AVAILABILITY: No access to a participating
                          site or unwilling to be followed at one
                          participating site for the duration of the
                          study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0116  Nevirapine
TRADE NAME OF SUBSTANCE   Drug 1 BI-RG-587
MANUFACTURERS             Drug 1: Boehringer Ingelheim Pharmaceuticals
                          Incorporated 900 Ridgebury Road Ridgefield,
                          CT 06877 Contact: Susannah Cort (203)
                          791-6063 Contact: Maureen Myers (203)
                          798-5583.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: MOTHERS: 100 mg as
                          single dose (if tolerated, another group of
                          patients will receive 200 mg as a single
                          dose). NEONATES: 2 mg/kg (estimated dose to
                          maintain a neonate blood lof >= 10 x IC50 (or
                          0.1 mcg/ml) over 7 days. If tolerated,
                          additional patients will receive 4 mg/kg.
                          Multiple doses, if utilized, will be
                          determined using data from the single dose c
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg tablets
                          and 10 mg/ml oral suspension
OTHER TREATMENT INFO.     END POINT: Drug-associated grade 3 or 4
                          toxicity; maintenance of antiviral drug
                          levels for the first week of life.
OTHER TREATMENT INFO.     DISCONTINUE: MOTHERS discontinue treatment
                          for the following reasons: 1. Pre-eclampsia
                          or pregnancy-induced hypertension requiring
                          intrapartum magnesium sulfate. 2. Severe
                          maternal infection with sequelae of shock
                          (e.g., acute respiratory disease,
                          hypotension). 3. Uncontrolled hypertension.
                          4. Intrapartum complication requiring
                          anticoagulation therapy. 5. Intrapartum
                          seizures. 6. Condition whereby mother is
                          unable to tolerate oral study drug. 7. Active
                          opportunistic infection and/or serious
                          bacterial infection. 8. Unacceptable
                          toxicity. NEONATES discontinue treatment for
                          the following reasons: 1. Severe congenital
                          malformations or other conditions not
                          compatible with life. 2. Severe anemia or
                          hypovolemia requiring volume replacement
                          and/or blood product therapy. 3. Severe
                          hyperbilirubinemia necessitating transfusion
                          or volume replacement. 4. Documented or
                          suspected serious infectious, cardiac,
                          respiratory, or metabolic illness, or other
                          immediate life-threatening condition. 5.
                          Unacceptable toxicity.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY/PREVENTION &
                          CONTROL/TRANSMISSION
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Middle Age
MESH HEADING              Pregnancy
MESH HEADING              Pregnancy Complications, Infectious
MESH HEADING              Pyridines/*ADVERSE EFFECTS/PHARMACOKINETICS
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
LAST REVISION DATE        941207
ENTRY MONTH               9411
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 941103
                          ACTU: 4601.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 941103 ACTU:
                          4301.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 941103 ACTU: 5031.
 
25
UNIQUE IDENTIFIER         NIH/00677
PROTOCOL ID NUMBERS       NIAID ACTG 245
PROTOCOL TITLE            A Comparative Study of Combination
                          Antiretroviral Therapy in Children and
                          Adolescents with Advanced HIV Disease.
VERSION NUMBER & DATE     2 (940719)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Burchett S
PROTOCOL CHAIRS           CO-CHAIR  Luzuriaga K
GENERAL DESCRIPTION       PURPOSE: To compare the antiviral activity,
                          safety, toxicity, and steady-state
                          pharmacokinetics of zidovudine, didanosine,
                          and nevirapine used in combination in
                          patients with HIV infection.
GENERAL DESCRIPTION       RATIONALE: The duration of clinical benefit
                          from zidovudine (AZT) may be limited because
                          of development of viral resistance to the
                          drug. Use of combination antiretroviral
                          therapy potentially can reduce viral load and
                          prevent emergence of multidrug resistance.
GENERAL DESCRIPTION       METHODOLOGY: In Stage 1 of the study, a
                          minimum of 22 patients are randomized to each
                          of three treatment arms: didanosine (ddI)
                          plus AZT plus nevirapine (NVP); ddI plus AZT;
                          and ddI plus NVP. After 12 weeks of
                          treatment, the study proceeds to Stage 2
                          provided at least 40 percent of patients in
                          Stage 1 showed a reduction of at least 40
                          percent from baseline ICD p24 antigen of >=
                          70 pg/ml AND fewer than two patients
                          experienced grade 4 rash. Patients in Stage 1
                          continue treatment for an additional 36
                          weeks. In Stage 2, additional patients are
                          randomized to each original treatment regimen
                          until a maximum of 130 patients per arm have
                          been entered. Stage 2 patients receive
                          treatment for at least 48 weeks.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection as evidenced by
                          positive viral culture, p24 antigen >= 30
                          pg/ml, proviral DNA on PCR, or two positive
                          antibody tests determined by ELISA with one
                          test confirmed by Western blot. 2. Disease
                          progression defined by growth failure OR
                          neurodevelopmental or neuropsychological
                          regression OR two or more AIDS-defining
                          opportunistic infections OR absolute CD4
                          cells <= 14 percent or a confirmed 50 percent
                          reduction in CD4 cells from a previous value
                          of >= 20 percent within 24 weeks prior to
                          study entry. 3. At least 24 weeks prior
                          cumulative nucleoside analog antiretroviral
                          monotherapy or combination therapy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 42003
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Drug Combination; Drug Tolerance;
                          Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination drug therapy,
                          Combination pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 390 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until 48 weeks
                          after enrollment of last patient.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 73/390 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 44 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Progressive HIV disease. 2. At least
                          24 weeks prior cumulative nucleoside analog
                          antiretroviral monotherapy or combination
                          therapy. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 7.0 g/dl. (EPO and transfusion
                          allowed).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 25000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          (Patients relying on CD4 value as evidence of
                          disease progression must have absolute CD4
                          cells <= 14 percent or a confirmed 50 percent
                          reduction in CD4 cells from previous value of
                          >= 20 percent within 24 w
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 15 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 15 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 35 ml/min. /1.73 m2.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 250 cells/mm3.
                          Pancreatic amylase < 2 x ULN.
PATIENT AGE               AGE: 06 Months - 20 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Transfusion.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Erythropoetin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of clinical pancreatitis. 2. History
                          of grade 2 or worse peripheral neuropathy.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 05 Months. 21 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Acute treatment
                          for a serious bacterial, viral, or
                          opportunistic infection within 14 days prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded (unless
                          exemption made by study chair): 1. Oral
                          anticoagulants (warfarin, dicumarol). 2. Oral
                          contraceptives. 3. Digitalis glycosides. 4.
                          Phenytoin. 5. Theophylline.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active malignancy requiring chemotherapy. 2.
                          Currently receiving therapy in an ACTG
                          primary therapy or salvage protocol who have
                          NOT met an endpoint on that study. 3. Known
                          intolerance (other than hematologic) or
                          toxicity to ddI, AZT, or NVP at the doses
                          used in this study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0116  Nevirapine
MANUFACTURERS             Drug 1: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 3: Boehringer Ingelheim Pharmaceutical
                          Incorporated 900 Ridgebury Road Ridgefield,
                          CT 06877 Contact: Dr Maureen Myers (203)
                          798-5583.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 mg/m2 (or
                          placebo) BID for 48 weeks. Drug 2: 180 mg/m2
                          (or placebo) TID for 48 weeks. Drug 3: 120
                          mg/m2 (or placebo) BID for 48 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 200 mg/m2. Drug 2: 540
                          mg/m2. Drug 3: 240 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, pediatric powder
                          for solution and 25 and 50 mg tablets. Drug
                          2: Oral, flavored syrup and 100 mg capsules.
                          Drug 3: Oral, 10 mg/ml bottles and 50 and 100
                          mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 12 weeks
                          (Stage 1); Minimum of 48 weeks (Stage 2).
OTHER TREATMENT INFO.     END POINT: Primary: Virologic efficacy,
                          safety, and pharmacokinetics /
                          pharmacodynamics of combination therapy.
                          Secondary: Clinical response to combination
                          therapy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Unacceptable
                          toxicity.
OTHER TREATMENT INFO.     MODIFICATION: o For hemoglobin < 7.0 g/dl:
                          hold AZT until toxicity resolves, then resume
                          at 50 percent dose. o For neutrophils < 250
                          cells/mm3: hold AZT until toxicity resolves,
                          then resume at 50 percent dose. If
                          neutropenia persists for > 14 days or recurs
                          within 30 days or > three times in 6 months,
                          hold AZT and ddI until toxicity resolves,
                          then resume both drugs at 50 percent dose. If
                          neutropenia persists for 14 additional days,
                          hold all study drugs until toxicity resolves,
                          then restart all drugs at 50 percent dose. If
                          neutropenia continues, discontinue study
                          drugs permanently. o For grade 3 or 4
                          myositis or headache: hold AZT until toxicity
                          resolves to grade 2 or better, then resume at
                          50 percent dose. If grade 3 or 4 myositis or
                          headache persists for > 7 days or recurs
                          within 30 days or > three times in 6 months,
                          hold AZT and ddI until toxicity resolves to
                          grade 2 or better, then resume both drugs at
                          50 percent dose. If toxicity persists for 7
                          additional days or recurs within 30 days,
                          hold all study drugs until toxicity resolves,
                          then resume all study drugs at 50 percent
                          dose. If grade 3 or 4 toxicity still persists
                          or recurs, discontinue all study drugs
                          permanently. o For grade 3 or 4 nausea,
                          vomiting, diarrhea, hyperamylasemia, or
                          peripheral neuropathy: hold ddI until
                          toxicity resolves to grade 2 or better, then
                          resume at 50 percent dose. For persistent or
                          recurrent toxicity, follow the same
                          management pattern as for myositis. o For
                          grade 3 or 4 thrombocytopenia or
                          hyperbilirubinemia: hold NVP until toxicity
                          resolves to grade 2 or better, then resume at
                          50 percent dose. If grade 3 or 4 toxicity
                          persists for > 7 days or recurs within 30
                          days or > three times in 6 months, hold NVP
                          and AZT until toxicity resolves to grade 2 or
                          better, then resume both drugs at 50 percent
                          dose. If toxicity persists or recurs, hold
                          and then discontinue all study drugs.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Didanosine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Pyridines/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Zidovudine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9410
ALABAMA                   University of Alabama at Birmingham School of
                          Medicine 751 CHT / University Station
                          Birmingham, AL 35294 Contact: Michael Cooney
                          (205) 939-9552 Contact: beeper (205) 869-9524
                          OPEN 941011 ACTU: 5046.
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          941107 ACTU: 5048.
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 941031
                          ACTU: 4601.
CALIFORNIA                UCSF / Moffitt Hospital 602 / Pediatrics 505
                          Parnassus / Box 0105 San Francisco, CA
                          94143-0105 Contact: Debbie Trevithick (415)
                          476-6480 OPEN 940921 ACTU: 4501.
CALIFORNIA                Children's Hospital Oakland 747 Fifty Second
                          Street Oakland, CA 94609-1809 Contact: Jim
                          Riddel (510) 428-3000 X 282Contact: (510)
                          539-6311 X PagOPEN 940919 ACTU: 4504.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 940919 ACTU:
                          7001.
CONNECTICUT               Univ of Connecticut Farmington / Univ of CT
                          Health Center 263 Farmington Avenue
                          Farmington, CT 06032 Contact: Lorraine Wells
                          (203) 679-2320 OPEN 941014 ACTU: 7303.
CONNECTICUT               Yale University School of Medicine PO Box
                          3333 / 333 Cedar Street New Haven, CT
                          06510-8064 Contact: Unspecified (203)
                          737-4040 OPEN 940823 ACTU: 5038.
DISTRICT OF COLUMBIA      Children's National Medical Center / Special
                          Immuno Svc Suite 2108 / 111 Michigan Avenue
                          NW Washington, DC 20010-2970 Contact: Sandra
                          Jones (202) 884-3682 OPEN 941107 ACTU: 7101.
DISTRICT OF COLUMBIA      Howard University Hospital 2041 Georgia
                          Avenue NW Washington, DC 20060 Contact: Dr
                          Helga Finke (202) 865-1248 OPEN 940919 ACTU:
                          5044.
FLORIDA                   Northeast Florida AIDS Program / Div of
                          Pediatric Inf Dis/Im 653-1 W 8th Street
                          Jacksonville, FL 32209 Contact: Michelle
                          Eagle (904) 549-3051 OPEN 941107 ACTU: 5051.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 940923 ACTU: 4201.
ILLINOIS                  University of Illinois at Chicago 840 S Wood
                          Street Chicago, IL 60612 Contact: Patricia
                          Naughton (312) 996-1778 OPEN 940919 ACTU:
                          5028.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 940829 ACTU: 4001.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 941005 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 941005 ACTU: 7201.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street / SHU-Main 3
                          Springfield, MA 01199 Contact: MaryPat Toye
                          (413) 784-5399 OPEN 941005 ACTU: 7302.
MASSACHUSETTS             University of Massachusetts Medical School /
                          Dept of Peds 55 Lake Avenue North Worcester,
                          MA 01655-0001 Contact: Joanne Shepard (508)
                          856-1692 OPEN 940808 ACTU: 7301.
MASSACHUSETTS             Children's Hospital 300 Longwood Avenue /
                          Carnegie 3 Boston, MA 02115 Contact: Robert
                          Bishop (617) 735-8198 OPEN 940815 ACTU: 2901.
MARYLAND                  University of Maryland School of Medicine /
                          Pediatrics 120 Penn Street Baltimore, MD
                          21201 Contact: Sue Lovelace (410) 706-8220
                          OPEN 941103 ACTU: 3702.
MARYLAND                  The Johns Hopkins University ( Pediatrics )
                          600 North Wolfe Street Baltimore, MD 21287
                          Contact: Laura J Belcher (410) 955-9749 OPEN
                          941123 ACTU: 3701.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Charnell
                          Cromer (313) 745-5565 OPEN 940927 ACTU: 5041.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 941013 ACTU:
                          4701.
NEW JERSEY                Robert Wood Johnson University Hospital /
                          UMDNJ One Robert Wood Johnson Place CN19 New
                          Brunswick, NJ 08903-0019 Contact: Ida Kechula
                          (908) 937-7894 OPEN 940921 ACTU: 5032.
NEW YORK                  Beth Israel Medical Center / Pediatrics First
                          Avenue at 16th Street Dazian Pavilion Tenth
                          Floor New York, NY 10003 Contact: Ann Marshak
                          (212) 420-4432 OPEN 941007 ACTU: 4302.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue / Pediatric
                          New York, NY 10016 Contact: Nagamah Deygoo
                          (212) 263-6426 OPEN 940919 ACTU: 4401.
NEW YORK                  Cornell Medical Center N-834 / Pediatric
                          Infectious Disease 1300 York Avenue New York,
                          NY 10021 Contact: Tony Hinds (212) 746-3326
                          OPEN 941207 ACTU: 5019.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940909 ACTU:
                          4301.
NEW YORK                  Incarnation Children's Ctr / c/o Columbia
                          Presb Med Ctr 142 Audubon Avenue New York, NY
                          10032 Contact: Pam Clark (212) 928-2228 OPEN
                          941115 ACTU: 4103.
NEW YORK                  The Columbia Presbyterian Medical Hosp
                          (Pediatric) 622 West 168th St Room 1161 New
                          York, NY 10032-3796 Contact: Kathy A Shea
                          (212) 305-7222 OPEN 941115 ACTU: 4101.
NEW YORK                  Harlem Hospital 506 Lenox Avenue New York, NY
                          10037 Contact: Rick Urbano (212) 939-4040
                          Contact: (212) 939-4045 OPEN 941014 ACTU:
                          5006.
NEW YORK                  Bronx Lebanon Hospital Center / Department of
                          Pediatrics 1650 Selwyn Avenue Room 2C Bronx,
                          NY 10457 Contact: Patrice Edwards-Cihak (718)
                          960-1015 OPEN 940912 ACTU: 6901.
NEW YORK                  King's County Hospital Center / SUNY HSCB 450
                          Clarkson Avenue Brooklyn, NY 11203 Contact:
                          Helen Bergin (718) 245-3342 Contact: (718)
                          245-3341 Contact: (718) 245-4485 OPEN 941014
                          ACTU: 5035.
NEW YORK                  SUNY at Brooklyn / Health Science Center /
                          Pediatrics 450 Clarkson Avenue / Box 24
                          Brooklyn, NY 11203 Contact: Barbara Driscoll
                          (718) 270-3081 OPEN 940830 ACTU: 5008.
NEW YORK                  Children's Hospital at Albany Medical Center
                          22 New Scotland Avenue Albany, NY 12208
                          Contact: Mary Ellen Adams (518) 432-1501 OPEN
                          941114 ACTU: 5042.
OHIO                      Children's Hospital 700 Children's Drive
                          Columbus, OH 43205-2696 Contact: Jane Hunkler
                          (614) 722-4460 Contact: (614) 722-6050 OPEN
                          941014 ACTU: 2302.
OTHER                     Ramon Ruiz Arnau University Hospital Laurel
                          Avenue Bayamon, PR 00619 Contact: Leticia
                          Diaz (809) 798-2733 OPEN 941017 ACTU: 5033.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 940907 ACTU: 5031.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          940916 ACTU: 6601.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 941116 ACTU: 6701.
RHODE ISLAND              Rhode Island Hospital / Brown University 593
                          Eddy Street Providence, RI 02903 Contact:
                          Cathy Kneut (401) 467-9884 OPEN 941123 ACTU:
                          5047.
SOUTH CAROLINA            Medical University of South Carolina Clinical
                          Science Building / 171 Ashley Avenue
                          Charleston, SC 29425-3312 Contact: Genny
                          Connelly (803) 792-2385 OPEN 940923 ACTU:
                          5037.
 
26
UNIQUE IDENTIFIER         NIH/00675
PROTOCOL ID NUMBERS       NIAID ACTG 244
PROTOCOL TITLE            A Double-Blinded, Randomized Trial Comparing
                          Zidovudine (AZT) Versus AZT Plus Didanosine
                          (ddI) Versus AZT Plus ddI Plus Nevirapine in
                          Asymptomatic Patients on AZT Monotherapy Who
                          Develop a Mutation at Codon 215 of HIV
                          Reverse Transcriptase in Serum/Plasma Viral
                          RNA.
VERSION NUMBER & DATE     2 (931217)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Merigan TC
PROTOCOL CHAIRS           CO-CHAIR  Mayers DL
GENERAL DESCRIPTION       PURPOSE: To validate that the alteration of
                          codon 215 of reverse transcriptase in plasma
                          virus precedes the increase in viral burden
                          as measured in the peripheral blood and the
                          decline in CD4 count that have been observed
                          in association with clinical failure on
                          zidovudine (AZT). To determine whether
                          alternative regimens of antiretroviral agents
                          alter the course of viral burden as measured
                          in the peripheral blood and CD4 changes in
                          patients with HIV infection. To obtain
                          further data on the safety and immunologic
                          and virologic response to
                          AZT/didanosine/nevirapine.
GENERAL DESCRIPTION       RATIONALE: Of the HIV-1 mutations reported to
                          be associated with zidovudine resistance, the
                          mutation at codon 215 of the reverse
                          transcriptase gene is the most commonly
                          occurring and has the greatest impact on
                          susceptibility. When this mutation appears, a
                          change in drugs may prevent further
                          immunologic and virologic deterioration.
GENERAL DESCRIPTION       METHODOLOGY: Initially, all patients receive
                          AZT alone. After detection of a 215 mutation
                          in plasma RNA, patients are randomized to one
                          of three treatment arms: AZT alone, AZT plus
                          ddI, or AZT/ddI plus nevirapine. Patients are
                          followed every 8 weeks and receive treatment
                          for up to 4 years.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Asymptomatic HIV infection
                          documented by ELISA. 2. CD4 count 300-600
                          cells/mm3. 3. No plasma/serum PCR for codon
                          215 mutation at screening. 4. AZT monotherapy
                          (minimum 300 mg/day) for at least 1 month
                          (uninterrupted) but no more than 2 years
                          immediately prior to study entry.
ELIGIBILITY               ASYM.
OTHER PROTOCOL NUMBERS    IND 42,003
STUDY DESIGN              Randomized; Placebo-Controlled; 3-Arm
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 300 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 4 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 139/300 (941207).
PROTOCOL DETAILS          STUDY DURATION: 4 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 47 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic HIV infection. 2. CD4
                          count 300-600 cells/mm3. 3. No plasma/serum
                          PCR for codon 215 mutation at screeing. 4.
                          Prior AZT monotherapy. NOTE: All Department
                          of Defense-eligible patients must be at least
                          18 years of age. Enrollment of women is
                          encouraged. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10 g/dl. (men); >= 9.0 g/dl
                          (women). No transfusion within the preceding
                          two weeks.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 300 - 600 cells/mm3. (
                          300 - 400 - 500 - 600 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 75 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. Total serum amylase <= 1.5 x ULN
                          (if serum amylase > 1.5 x ULN, lipase <= 1.5
                          x ULN or pancreatic amylase may be used to
                          qualify). Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Limited
                          localized radiation therapy to the skin.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT (minimum 300
                          mg/day) for at least 1 month (uninterrupted)
                          but no more than 2 years immediately prior to
                          study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii
                          pneumonia. 2. Antibiotics, antifungals, and
                          antiviral medications, as clinically
                          indicated. 3. Regularly prescribed medication
                          such as antipyretics, analgesics, allergy
                          medications, antidepressants, sleep
                          medications, oral contraceptives, or any
                          other medications deemed appropriate by the
                          primary care provider.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of pancreatitis. 2. Chronic diarrhea
                          for at least 4 of the 7 days immediately
                          prior to study entry. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Illicit drug or alchohol
                          abuse.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy other than limited localized therapy
                          to skin.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior therapy
                          with nucleoside or nonnucleoside
                          antiretroviral agents other than AZT. 2.
                          Blood transfusion within the preceding 2
                          weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          cytotoxic chemotherapy. 2. Biologic response
                          modifiers (such as interferon, ampligen, or
                          PEG-IL2). 3. Anti-HIV agents other than study
                          drugs. 4. Other investigational agents. 5.
                          Foscarnet unless clinically indicated for
                          unresponsive herpes virus infection. 6.
                          Chronic antacid or H-2 blocker use. 7.
                          Rifampin or rifamycin class agents. 8.
                          Antibiotics containing clavulanic acid.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Symptomatic grade 2 or worse peripheral
                          neuropathy. 2. Unable to swallow capsules and
                          tablets. 3. Other medical condition that
                          contraindicates study participation.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0116  Nevirapine
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle Park, NC 27709
                          Contact: Mary Maha Elkins (919) 248-3294.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
MANUFACTURERS             Drug 3: Boehringer Ingelheim Pharmaceuticals
                          Incorporated 900 Ridgebury Road Ridgefield,
                          CT 06877 Contact: Susannah Cort (203)
                          791-6063 Contact: Maureen Myers (203)
                          798-5583.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg q 8 hr for up
                          to 4 years. Drug 2: 200 mg (or placebo) q 12
                          hr for up to 4 years. Patientweighing <= 60
                          kg receive 125 mg (or placebo) q 12 hr. Drug
                          3: 200 g (or placebo) daily for the first 8
                          weeks, then 40(or placebo) daily for up to 4
                          years
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 400 mg.
                          Drug 3: 200 mg for the first 8 weeks, then
                          400 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules.
                          Drug 2: Oral; 25, 50 and 100 mg tablets. Drug
                          3: Oral, 200 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 4 years.
OTHER TREATMENT INFO.     END POINT: Primary: Comparison of the slope
                          of CD4 counts over time, before and after
                          emergence of 215 mutation. Secondary: Change
                          in proviral DNA in CD4 cells or in serum
                          viral RNA of >= 1.0 log, change in p24 and
                          beta-2 microglobulin, dose-limiting toxicity,
                          correlation of baseline prognostic markers
                          with development of 215 mutation, virologic
                          and immunologic changes. ddI treatment is
                          discontinued for the following reasons: 1.
                          Development of an AIDS-defining condition. 2.
                          Dose-limiting toxicity. 3. Decline in CD4
                          counts by more than 50 percent on two
                          consecutive counts at least 72 hours apart.
                          4. Pregnancy. 5. Medical recommendation of
                          the treating physician. 6. Discontinuation of
                          study by sponsor, FDA, or pharmaceutical
                          company, or desire of patient to withdraw.
OTHER TREATMENT INFO.     MODIFICATION: Dose is held or reduced for
                          specific toxicities.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Burroughs Wellcome,
                          Bristol-Myers Squibb Company.
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pyridines/*THERAPEUTIC USE
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9401
CALIFORNIA                University of California at Los Angeles
                          School of Medicine 60051 CHS / 10833 Le Conte
                          Avenue Los Angeles, CA 90024-1793 Contact:
                          Susan G McCarthy (310) 825-1301 OPEN 940210
                          ACTU: 0601.
CALIFORNIA                Harbor General / REI Lab / UCLA 1124 West
                          Carson Street Torrance, CA 90502 Contact:
                          Sally Kruger (310) 222-3848 Contact: Rick
                          Johnson OPEN 940210 ACTU: 0603.
CALIFORNIA                AIDS Community Research Consortium 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harris (415) 364-5653 OPEN
                          940216 ACTU: 0505.
CALIFORNIA                Santa Clara Valley Med Ctr / ACRC 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harriss (415) 364-5653 OPEN
                          940311 ACTU: 0506.
CALIFORNIA                Kaiser Permanente Medical Group / Stanford
                          University 2590 Geary Boulevard San
                          Francisco, CA 94115 Contact: Gretchen Van
                          Raalte (415) 202-3482 OPEN 940531 ACTU: 0502.
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 940114
                          ACTU: 0501.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 940201 ACTU: 5701.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 941115
                          ACTU: 5201.
IOWA                      University of Iowa / UH Nursing W321 GH
                          Internal Medicine SW34-GH Iowa City, IA 52242
                          Contact: Julie Katseres (319) 353-8441 OPEN
                          940323 ACTU: 1504.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 941007 ACTU: 2601.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02115 Contact: Sheila Hussey (617)
                          735-4103 OPEN 941207 ACTU: 0102.
MARYLAND                  Walter Reed Army Medical Center 1600 East
                          Gude Drive Room 222 Rockville, MD 20852
                          Contact: Lori Abrams (301) 217-9410 OPEN
                          940210 ACTU: 5502.
MARYLAND                  Fitzsimmons Army Medical Center / Walter Reed
                          Army Hospital 1600 East Gude Drive Room 222
                          Rockville, MD 20852 Contact: Lori Abrams
                          (301) 217-9410 X 103OPEN 940923 ACTU: 5508.
MARYLAND                  National Naval Medical Center 8901 Wisconsin
                          Avenue Bethesda, MD 20899-5000 Contact:
                          Unspecified (301) 295-5385 OPEN 940310.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 940425 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 940425 ACTU:
                          0202.
MINNESOTA                 St Paul-Ramsey Medical Center 640 Jackson
                          Street St Paul, MN 55101 Contact: Ray Nelson
                          (612) 221-1280 OPEN 940418 ACTU: 1503.
MINNESOTA                 Hennepin County Med Clinic / Univ of
                          Minnesota Hosp Clinic 420 Delaware Street SE
                          / Room G255 Mayo Building Minneapolis, MN
                          55415 Contact: Renee St Jacques (612)
                          373-1810 OPEN 940406 ACTU: 1502.
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 940308 ACTU:
                          1501.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          941102 ACTU: 3201.
NORTH CAROLINA            Wake County Department of Health Hosp South
                          Room 0207 Box 3284 Durham, NC 27710 Contact:
                          Kelley Rayle (919) 250-1035 OPEN 941102 ACTU:
                          3206.
NORTH CAROLINA            Carolinas Medical Center / Department of
                          Internal Medicine 1000 Blythe Blvd AHEC Room
                          507 Charlotte, NC 28203 Contact: Joan Connell
                          (704) 355-5292 Contact: (704) 355-3165 OPEN
                          941123 ACTU: 3204.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Frances Tennant (402) 559-5750 OPEN
                          940323 ACTU: 1505.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 940317 ACTU: 0401.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940531 ACTU: 1906.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940426 ACTU: 1901.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940531
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940531
                          ACTU: 1904.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940426
                          ACTU: 1902.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940531 ACTU: 1903.
NEW YORK                  Montefiore Medical Center Adolescent AIDS
                          Program 111 East 210th Street Bronx, NY
                          10467-2490 Contact: Dina Monte (718) 882-0023
                          OPEN 941116 ACTU: 5049.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          940822 ACTU: 7403.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 940822 ACTU: 7401.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          940822 ACTU: 7402.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 940308 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          940124 ACTU: 1102.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940201 ACTU: 1101.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941006
                          ACTU: 2301.
OHIO                      Medical College of Ohio / Department of
                          Medicine 3000 Arlington Avenue Toledo, OH
                          43699 Contact: Lynn Lipton (419) 381-3729
                          Contact: (419) 381-4328 OPEN 940317 ACTU:
                          2502.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940202 ACTU: 2501.
OHIO                      Metrohealth Medical Center / Case Western
                          Reserve Univ 2500 MetroHealth Drive
                          Cleveland, OH 44109-1998 Contact: Nancy
                          Frantz (216) 459-5136 OPEN 940511 ACTU: 2503.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 940418 ACTU: 6201.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 940502 ACTU: 6202.
 
27
UNIQUE IDENTIFIER         NIH/00581
PROTOCOL ID NUMBERS       NIAID ACTG 243
PROTOCOL TITLE            A Phase II Multicenter Study Comparing
                          Antiretroviral Therapy Alone to
                          Antiretroviral Therapy Plus Cytosine
                          Arabinoside (Cytarabine; Ara-C) for the
                          Treatment of Progressive Multifocal
                          Leukoencephalopathy (PML) in Human
                          Immunodeficiency Virus (HIV)-Infected
                          Subjects.
VERSION NUMBER & DATE     2 (940825)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Hall C
PROTOCOL CHAIRS           CO-CHAIR  Timpone J
GENERAL DESCRIPTION       PURPOSE: To compare the safety and efficacy
                          of antiretroviral therapy (zidovudine plus
                          either didanosine or dideoxycytidine) versus
                          antiretroviral therapy plus intravenous
                          cytarabine (Ara-C) versus antiretroviral
                          therapy plus intrathecal Ara-C in the
                          maintenance or improvement of neurological
                          function over 6 months in HIV-infected
                          individuals who have developed progressive
                          multifocal leukoencephalopathy (PML). To
                          compare the effect of these three treatment
                          regimens on Karnofsky score and MRI studies.
GENERAL DESCRIPTION       RATIONALE: The effectiveness of Ara-C in the
                          treatment of PML, caused by a human DNA
                          papovavirus (designated JC virus) infection,
                          has not been determined, although the most
                          encouraging results have occurred with
                          intrathecal administration of the drug.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive antiretroviral therapy alone (AZT
                          plus ddI or ddC), antiretroviral therapy plus
                          intravenous Ara-C, or antiretroviral therapy
                          plus intrathecal Ara-C. All patients receive
                          24 weeks of antiretroviral therapy. Beginning
                          at week 2, patients on the intravenous Ara-C
                          arm receive daily infusions of Ara-C over 5
                          days, with cycles repeating every 21 days.
                          Patients on the intrathecal Ara-C arm receive
                          single administrations of Ara-C at weeks 2,
                          3, 4, 5, 6, 8, 10, 12, 16, 20, and 24. A
                          brain biopsy confirmation or in situ
                          hybridization will be required within 7 days
                          after study entry. Patients are followed
                          every 4 weeks.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Progressive multifocal leukoencephalopathy (
                          PML ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot. 2. Clinical
                          presentation and MRI compatible with PML
                          within the past 2 months, confirmed by brain
                          biopsy or in situ hybridization by 14 days
                          after study entry. 3. No other current active
                          opportunistic infections requiring systemic
                          therapy. NOTE: Patients on stable maintenance
                          or prophylaxis therapy for opportunistic
                          infections for at least 2 weeks prior to
                          study entry are permitted.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 44,084
STUDY DESIGN              Randomized; Open Label; Multicenter; Drug
                          Tolerance; Comparative administration route
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Combination drug therapy, Administration
                          route comparison.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients. (30 patients
                          on each of three treatment arms)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until last
                          patient enrolled completes treatment.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 16/90 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 12 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Confirmed PML. 3.
                          No other current active opportunistic
                          infections requiring systemic therapy. 4.
                          Life expectancy of at least 3 months. NOTE: A
                          durable power of attorney is recommended
                          where severe neurologic or psychiatric
                          impairment can be foreseen while the patient
                          is on study. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Local
                          radiation therapy for mucocutaneous Kaposi's
                          sarcoma.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Local
                          intralesional chemotherapy for mucocutaneous
                          Kaposi's sarcoma. 2. Topical antifungals,
                          clotrimazole, ketoconazole, fluconazole, and
                          amphotericin B for treatment of mucosal and
                          esophageal candidiasis. 3. Foscarnet for
                          newly developed CMV infection, only after
                          discussion with the protocol chair. 4.
                          Prophylactic and maintenance therapy for
                          other opportunistic infections, provided
                          patients are considered clinically stable. 5.
                          No more than 1000 mg/day acyclovir for herpes
                          simplex. 6. Antibiotics for bacterial
                          infections as clinically indicated. 7.
                          Antipyretics, analgesics, and antiemetics.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of allergy or intolerance to G-CSF.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Any prior Ara-C.
                          Excluded within 14 days prior to study: 1.
                          Ganciclovir or foscarnet. 2. Interferon. 3.
                          Antiretroviral medications other than AZT,
                          ddI, or ddC. 4. Experimental medications for
                          treatment of PML.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Ganciclovir. 2. Interferon. 3. Systemic
                          chemotherapy other than Ara-C (unless
                          specifically allowed). 4. Antiretroviral
                          medications other than AZT, ddI, or ddC.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Current active cryptococcal meningitis,
                          cytomegaloviral encephalitis, toxoplasmosis
                          encephalitis, CNS lymphoma, or neurosyphilis.
                          NOTE: Patients on maintenance therapy for
                          cryptococcal meningitis or toxoplasmosis
                          encephalitis that has been stable for 4
                          months are permitted. 2. Conditions that
                          seriously increase risk of a surgical
                          procedure (e.g., coagulopathy, severe
                          thrombocytopenia). 3. Any other disease that
                          would interfere with evaluation of the
                          patient. 4. Other life-threatening
                          complications likely to cause death in < 3
                          months.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0038  Cytarabine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0015  Dideoxycytidine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0086  Granulocyte
                          colony-stimulating factor
TRADE NAME OF SUBSTANCE   Drug 1 Cytosar-U
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
TRADE NAME OF SUBSTANCE   Drug 3 Hivid
TRADE NAME OF SUBSTANCE   Drug 4 Videx
TRADE NAME OF SUBSTANCE   Drug 5 Neupogen
MANUFACTURERS             Drug 1: The Upjohn Company 301 Henrietta
                          Street Kalamazoo, MI 49001 Contact: Dr Robert
                          Earhart (616) 385-7677.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Kathryn Pattishall (919) 315-4440 Contact: Dr
                          Andy Sopchak (919) 315-3891.
MANUFACTURERS             Drug 3: Hoffmann-La Roche Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Dr Miklos Salgo (201) 812-3587.
MANUFACTURERS             Drug 4: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
MANUFACTURERS             Drug 5: Amgen Inc 1840 DeHavilland Drive
                          Thousand Oaks, CA 91320-1789 Contact: Susan
                          Armstrong (805) 447-4175.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Intravenous: 4 mg/kg
                          daily for 5 days, repeated every 2days for a
                          total of eight cycles. Intrathecal: 50 mg
                          through an Ommaya reservoir at weeks 2, 3,
                          46, 8, 10, 12, 16, 20, and 24. Drug 2: 300 mg
                          TID for a total of 24 weeks. Drug 3: 0.75 mg
                          TID for a total of 24 weeks. Drug 4: 125 mg
                          (if <= 60 kg) or 200 mg (if > 60 kg) BID for
                          a tof 24 weeks. Drug 5: 300 mcg daily until
                          ANC reaches 2000 cells/mm3, then tito
                          maintain the ANC in the 2000 to 10000
                          cells/mm3 range
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 2: 900 mg. Drug 3: 2.25
                          mg. Drug 4: 250 or 400 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV) or
                          intrathecal, 100 mg vials. Drug 2: Oral, 100
                          mg capsules.. Drug 3: Oral, 0.375 and 0.75 mg
                          tablets. Drug 4: Oral, 25, 50, and 100 mg
                          tablets.. Drug 5: Subcutaneous, 300 mcg/ml
                          vials
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Primary: Death. Secondary: Change
                          in neurologic function, change in Karnofsky
                          performance score, development of
                          drug-related toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Institution of prohibited
                          medications. 3. Recurrent or severe
                          persistent patient noncompliance. 4.
                          Pregnancy. 5. Development of CNS disorders
                          such as cryptococcal meningitis, toxoplasmic
                          encephalitis, CNS lymphoma, and
                          cytomegaloviral encephalitis, which could
                          confound neurological assessment. 6.
                          Diagnosis of PML not confirmed.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), The Upjohn Company,
                          Bristol-Myers Squibb Company.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Cytarabine/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Didanosine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Granulocyte Colony-Stimulating Factor/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Infusions, Intravenous
MESH HEADING              Injections, Spinal
MESH HEADING              Leukoencephalopathy, Progressive Multifocal/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zalcitabine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       147-94-4 (Cytarabine)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       62683-29-8 (Granulocyte Colony-Stimulating
                          Factor)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        941207
ENTRY MONTH               9404
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          940421 ACTU: 0802.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 940822 ACTU:
                          6101.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 940511 ACTU: 6401.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 940531
                          ACTU: 0901.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940413 ACTU: 2701.
MASSACHUSETTS             Massachusetts General Hospital / Harvard 55
                          Fruit Street Gray 5 Boston, MA 02114 Contact:
                          Ellen Godfrey (617) 726-5598 OPEN 940622
                          ACTU: 0101.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 940405 ACTU: 0201.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940602 ACTU:
                          2101.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          940415 ACTU: 3201.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940414 ACTU: 1801.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 940511 ACTU: 7501.
 
28
UNIQUE IDENTIFIER         NIH/00582
PROTOCOL ID NUMBERS       NIAID ACTG 242
PROTOCOL TITLE            A Phase II/III Double-Blind Study of
                          Amitriptyline and Mexiletine for Painful
                          Neuropathy in HIV Infection.
VERSION NUMBER & DATE     1 (931105)
TRIAL CATEGORY            Neurologic Manifestations
PROTOCOL CHAIRS           CHAIR  Kieburtz K
PROTOCOL CHAIRS           CO-CHAIR  Clifford D, Hall C, Max
GENERAL DESCRIPTION       PURPOSE: To assess the efficacy, safety, and
                          tolerability of amitriptyline hydrochloride
                          versus mexiletine hydrochloride in reducing
                          pain intensity in patients with HIV-related
                          painful peripheral neuropathy.
GENERAL DESCRIPTION       RATIONALE: No large-scale controlled clinical
                          trials of symptomatic therapy for painful
                          HIV-related neuropathy have been attempted.
                          Both amitriptyline and mexiletine have been
                          useful in the management of painful
                          neuropathies; however, both are associated
                          with certain toxicities. In this comparative
                          study of amitriptyline and mexiletine,
                          benztropine mesylate also will be included as
                          an active placebo to mimic the side effects
                          of the study drugs.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive amitriptyline, mexiletine, or
                          benztropine mesylate as an active placebo to
                          mimic the mild side effects associated with
                          both amitriptyline and mexiletine. Doses are
                          gradually increased over 4 weeks until a
                          minimum effective dose or MTD is reached,
                          then patients are treated for at least 4
                          additional weeks at the final dose before
                          gradually tapering off. Neurologic exams are
                          performed at screening and at the end of
                          treatment. Intensity of pain is rated twice
                          daily by the patient. Patients are followed
                          at weeks 2, 4, and 8, and at 10 days after
                          completely tapering off of drug.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Peripheral neuropathy.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA and confirmed by Western blot, positive
                          viral culture, or detectable serum p24
                          antigen. 2. Painful peripheral neuropathy,
                          indicated by - Primary symptoms of
                          symmetrical pain, burning, or tingling
                          discomfort in feet for at least 2 weeks, then
                          rated as either mild all the time or moderate
                          for at least 2 hours per day AND EITHER -
                          Dimished or absent ankle reflexes OR - Distal
                          diminution of vibration sensation in the legs
                          or pain or temperature sensation.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 44,014
STUDY DESIGN              Randomized; Placebo-Controlled;
                          Parallel-Group; 3-Arm; Drug Comparison; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy, Drug
                          efficacy, Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 240 patients. (80 patients
                          per treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately
                          10 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 56/240 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 47 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. Painful
                          peripheral neuropathy. NOTE: Patients in ACTG
                          blinded studies of dideoxynucleosides such as
                          ddI, ddC, and d4T are encouraged to enroll in
                          this study. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5.0 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5.0 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding.
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Allowed: Prior acupuncture.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Acupuncture.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Prior ddI, ddC,
                          or d4T, if on a stable dose for at least 8
                          weeks prior to study entry. 2. Prior
                          cimetidine if on a stable dose for at least 2
                          weeks prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Aspirin
                          and acetaminophen. 2. Nonsteroidal
                          anti-inflammatory agents. 3. Opiates. 4.
                          Pyridoxine (only if accompanied by
                          isoniazid). 5. ddI, ddC, and d4T if on a
                          stable dose. 6. AZT. 7. Cimetidine if on a
                          stable dose.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of cardiac disease. 3. History of
                          allergy to, or intolerance of, tricyclic
                          antidepressants, mexiletine, or benztropine.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug or alcohol abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          disopyramide. 2. Prior procainamide. 3. Prior
                          quinidine. 4. Prior tocainide. 5. Prior
                          flecainide acetate. 6. Prior encainide. 7.
                          Prior lidocaine. 8. Cisplatin or vincristine
                          within 8 weeks prior to study entry. 9.
                          Chloramphenicol, disulfiram, ethionamide
                          glutethimide, gold, hydralazine, iodoquinol,
                          metronidazole, nitrofurantoin, or ribavirin
                          within 8 weeks prior to study entry (only in
                          patients in whom the onset or clear worsening
                          of painful peripheral neuropathy was
                          attributed to taking these drugs). 10.
                          Heterocyclic or monoamine oxidase inhibitor
                          antidepressants within 4 weeks prior to study
                          entry. 11. More than 50 percent change in the
                          weekly dosage of any pain control medications
                          within 2 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Phenytoin
                          or carbamazepine. 2. Capsaicin. 3.
                          Heterocyclic or monoamine oxidase inhibitor
                          antidepressants. 4. Disopyramide. 5.
                          Procainamide. 6. Quinidine. 7. Tocainide. 8.
                          Flecainide acetate. 9. Encainide. 10.
                          Lidocaine. 11. Cisplatin. 12. Vincristine.
                          13. Chloramphenicol, disulfiram, ethionamide
                          glutethimide, gold, hydralazine, iodoquinol,
                          metronidazole, nitrofurantoin, or ribavirin
                          (only in patients in whom the onset or clear
                          worsening of painful peripheral neuropathy
                          was attributed to previously taking these
                          drugs). 14. Any investigational drugs other
                          than d4T (except with permission of the
                          protocol team). 15. Terfenadine (if
                          concurrent with ketoconazole).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Diabetes mellitus. 2. Neurological disease of
                          sufficient severity to confound the
                          evaluation of peripheral neuropathy, such as
                          myelopathy without neuropathy. (NOTE:
                          Patients with both myelopathy AND painful
                          peripheral neuropathy are eligible.) 3.
                          Electrocardiogram (EKG) indicating malignant
                          arrhythmia or cardiac conduction disturbances
                          (such as second or third degree AV block,
                          anterior hemi-block, or prolonged QT
                          interval). 4. Suicidal thoughts of sufficient
                          severity to require treatment with
                          antidepressant medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0197  Mexiletine hydrochloride
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0198  Benztropine mesylate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0169  Amitriptyline hydrochloride
TRADE NAME OF SUBSTANCE   Drug 1 Mexitil
TRADE NAME OF SUBSTANCE   Drug 2 Cogentin
TRADE NAME OF SUBSTANCE   Drug 3 Elavil
MANUFACTURERS             Drug 1: Boehringer Ingelheim Pharmaceuticals
                          Inc 900 Ridgebury Road / PO Box 368
                          Ridgefield, CT 06877 Contact: Dr Pedro
                          Urquilla (203) 791-6438.
MANUFACTURERS             Drug 2: Merck and Company Incorporated
                          Professional Services West Point, PA 19486
                          Contact: Professional Information (215)
                          661-7300 Contact: Prof Info / Call Collect
                          (215) 652-3298.
MANUFACTURERS             Drug 3: Stuart Pharmaceuticals Professional
                          Services Wilmington, DE 19897 Contact:
                          Professional Services (302) 886-2231.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 150 mg (or placebo)
                          nightly as starting dose, with upwatitration
                          over a period of 4 weeks to a maximum of 300
                          mg BID; followed by at least 4 additional
                          weeks at the final dose and tgradual tapering
                          off of drug. Drug 2: Minimum effective dose,
                          MTD, or 0.5 mg nightly as activplacebo, taken
                          on same schedule as mexiletine. Drug 3: 25 mg
                          (or placebo) nightly as starting dose, with
                          upwartitration over a period of 4 weeks to a
                          maximum of 100 mg nightfollowed by at least 4
                          additional weeks at the final dose and
                          tgradual tapering off of drug
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 150 mg - 600 mg. Drug
                          2: Up to 0.5 mg. Drug 3: 25 - 100 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 150 mg gelatin
                          capsules. Drug 2: Oral, 0.125 mg gelatin
                          capsules. Drug 3: Oral, 25 mg gelatin
                          capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: Approximately 10 weeks.
OTHER TREATMENT INFO.     END POINT: Primary: Decline in mean pain
                          intensity score between baseline and week 8
                          of treatment, toxicity. Secondary: Global
                          pain relief, mood, quality of life,
                          requirement for additional analgesic agents,
                          relation of drug level to pain intensity,
                          patient compliance.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Grade 3 or 4
                          drug-related toxicity. 2. Seizure. 3. Cardiac
                          conduction disturbance. 4. Malignant
                          arrhythmia. 5. Pregnancy.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 and 4 drug-related
                          toxicities: Hold study drug. If toxicity
                          resolves to grade 2 or better within 21 days,
                          then resume study drug at the next lower
                          dose. If the reduced toxicity improves even
                          further, then increase dose to the next
                          higher level. If toxicity does not resolve to
                          grade 2 or better after initially holding
                          drug for 21 days, or if the reduced toxicity
                          does not improve after 21 days at the next
                          lower dose, then discontinue study drug
                          permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Boehringer Ingelheim
                          Pharmaceuticals Inc.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Amitriptyline/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Benztropine/ANALOGS & DERIVATIVES/
                          *ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
                          THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Mexiletine/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Middle Age
MESH HEADING              Pain/*DRUG THERAPY
MESH HEADING              Parasympatholytics/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Peripheral Nervous System Diseases/
                          *COMPLICATIONS
CAS REGISTRY NUMBER       0 (Parasympatholytics)
CAS REGISTRY NUMBER       132-17-2 (benzatropine methanesulfonate)
CAS REGISTRY NUMBER       31828-71-4 (Mexiletine)
CAS REGISTRY NUMBER       50-48-6 (Amitriptyline)
LAST REVISION DATE        941207
ENTRY MONTH               9403
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 940308 ACTU: 5801.
CALIFORNIA                University of California at Los Angeles
                          School of Medicine 60051 CHS / 10833 Le Conte
                          Avenue Los Angeles, CA 90024-1793 Contact:
                          Susan G McCarthy (310) 825-1301 OPEN 940308
                          ACTU: 0601.
CALIFORNIA                Harbor General / REI Lab / UCLA 1124 West
                          Carson Street Torrance, CA 90502 Contact:
                          Sally Kruger (310) 222-3848 Contact: Rick
                          Johnson OPEN 940216 ACTU: 0603.
CALIFORNIA                Veterans Admin Hospital at San Diego / UCSD
                          Med Center 9500 Gilman Drive / # 0672 La
                          Jolla, CA 92093 Contact: Candace McIvor (619)
                          534-7170 OPEN 941107 ACTU: 0702.
CALIFORNIA                University of California San Diego 9500
                          Gilman Drive / Clinical Sciences Bldg
                          LaJolla, CA 92093-0672 Contact: Candace
                          McIvor (619) 534-7170 OPEN 940930 ACTU: 0701.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840OPEN 940707 ACTU: 0801.
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          940706 ACTU: 0802.
CALIFORNIA                Merrit-Peralta Medical Ctr/Adult Immunology
                          Clinic U of CA 450 30th Street Oakland, CA
                          94609 Contact: Bruce Ross (510) 273-8200
                          Contact: David Greenberg OPEN 940707 ACTU:
                          0804.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 940705 ACTU:
                          6101.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941004 ACTU:
                          6104.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 941017 ACTU: 6401.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 940906 ACTU: 5701.
DISTRICT OF COLUMBIA      Howard U Coll of Med / AIDS Minority
                          Infrastructure Program 2112 Georgia Avenue NW
                          Washington, DC 20059 Contact: Victoria Holly
                          -Trimmer (202) 806-4700 Contact: (202)
                          806-4755 OPEN 940705 ACTU: 5301.
IOWA                      University of Iowa / UH Nursing W321 GH
                          Internal Medicine SW34-GH Iowa City, IA 52242
                          Contact: Julie Katseres (319) 353-8441 OPEN
                          940627 ACTU: 1504.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940829 ACTU: 2701.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941017 ACTU: 2708.
ILLINOIS                  Illinois Masonic Med Ctr / Northwestern Univ
                          Med Schl Passavant Pavilion Room 823 / 303
                          East Superior Chicago, IL 60611 Contact:
                          Baiba L Berzins (312) 908-9636 OPEN 941006
                          ACTU: 2707.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940829 ACTU: 2702.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940701 ACTU: 2601.
MASSACHUSETTS             Massachusetts General Hospital / Harvard 55
                          Fruit Street Gray 5 Boston, MA 02114 Contact:
                          Ellen Godfrey (617) 726-5598 OPEN 940713
                          ACTU: 0101.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 OPEN 940701 ACTU: 0104.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 940701 ACTU: 0201.
MINNESOTA                 St Paul-Ramsey Medical Center 640 Jackson
                          Street St Paul, MN 55101 Contact: Ray Nelson
                          (612) 221-1280 OPEN 940701 ACTU: 1503.
MINNESOTA                 Hennepin County Med Clinic / Univ of
                          Minnesota Hosp Clinic 420 Delaware Street SE
                          / Room G255 Mayo Building Minneapolis, MN
                          55415 Contact: Renee St Jacques (612)
                          373-1810 OPEN 940701 ACTU: 1502.
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 940308 ACTU:
                          1501.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940809 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 940809
                          ACTU: 2102.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          941102 ACTU: 3201.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Frances Tennant (402) 559-5750 OPEN
                          940228 ACTU: 1505.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940701 ACTU: 1801.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 941011 ACTU: 7501.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 940804 ACTU:
                          1905.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940803 ACTU: 1906.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940804 ACTU: 1903.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940301 ACTU: 1901.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940808
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940804
                          ACTU: 1904.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940228
                          ACTU: 1902.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 941102 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941205 ACTU: 1102.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940701 ACTU: 1101.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940706 ACTU: 2501.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 941207 ACTU:
                          2401.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 940701 ACTU: 6202.
 
29
UNIQUE IDENTIFIER         NIH/00562
PROTOCOL ID NUMBERS       NIAID ACTG 240
PROTOCOL TITLE            A Randomized, Comparative Trial of Zidovudine
                          (AZT) Versus
                          2',3'-Didehydro-3'-deoxythymidine (Stavudine;
                          d4T) in Children With HIV Infection.
VERSION NUMBER & DATE     2 (940110)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
PROTOCOL CHAIRS           CHAIR  Kline M
PROTOCOL CHAIRS           CO-CHAIR  Van Dyke R
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To compare the relative
                          safety and tolerance of oral zidovudine (AZT)
                          versus oral stavudine (d4T) in symptomatic
                          HIV-infected children. SECONDARY: To compare
                          the clinical, virologic, and immunologic
                          responses between the two treatment groups,
                          and to obtain pharmacokinetic data for both
                          drugs.
GENERAL DESCRIPTION       RATIONALE: At present, AZT is considered the
                          drug of choice for initial treatment of most
                          children with HIV infection, although disease
                          progression or drug intolerance is associated
                          with its long-term use. In preliminary
                          studies in children, d4T, another HIV
                          inhibitor, has been well tolerated, although
                          an optimum dose has not been determined.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either oral AZT or oral d4T.
                          Treatment continues until the last patient
                          enrolled has received 52 weeks of therapy, or
                          until the study is terminated.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Evidence of HIV-1 infection as
                          follows: o Children younger than 15 months
                          must have one positive peripheral blood viral
                          isolation, with a second blood specimen
                          positive by qualitative culture, DNA-PCR, or
                          neutralizable p24 antigen assay. NOTE: Cord
                          blood is NOT acceptable. o Children older
                          than 15 months must have either of the above
                          criteria OR two positive tests for HIV
                          antibody by ELISA, with one test confirmed by
                          Western blot or immunofluorescence assay. 2.
                          Immunologic evidence of HIV disease as
                          follows: o Age < 12 months - < 1750 cells/mm3
                          o Ages 12-23 months - < 1000 cells/mm3 o Ages
                          2-6 - < 750 cells/mm3 AND/OR One or more of
                          the following clinical symptoms: o AIDS by
                          CDC criteria o Failure to thrive o Persistent
                          or recurrent oral candidiasis o
                          Thrombocytopenia o Two or more episodes of
                          herpes simplex infection (other than herpes
                          labialis) or one episode of herpes zoster o
                          Persistent diarrhea o Lymphoid interstitial
                          pneumonia and/or pulmonary lymphoid
                          hyperplasia (LIP/PLH complex) o
                          Cardiomyopathy o Nephropathy o Parotitis
                          (chronic parotid enlargement for 8 weeks or
                          longer after diagnosis of HIV o Splenomegaly
                          o Two secondary bacterial or fungal
                          infections such as septicemia, meningitis, or
                          pneumonia.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 43,550
STUDY DESIGN              Randomized; Double-Blind; 2-Arm; Dose
                          Comparison; Drug Comparison; Drug Tolerance;
                          Multicenter; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy, Pharmacokinetics, Comparative
                          toxicity, Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 230 patients. 06
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 52
                          weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 172/230 (941207).
PROTOCOL DETAILS          STUDY DURATION: Until 52 weeks after last
                          patient enrolled.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 63 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Symptomatic HIV infection. 2. No
                          more than 6 weeks of prior antiretroviral or
                          immunomodulator therapy (other than steroids
                          and IVIG). 3. Consent of parent or guardian.
                          NOTE: Coenrollment on another ACTG protocol
                          not involving antiretroviral therapy is
                          permitted. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 03 Months - 06 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Maternal
                          immunomodulator or antiretroviral therapy
                          (including during pregnancy). 2.
                          Antiretroviral therapy prior to 2 months. 3.
                          Up to 6 weeks of prior antiretroviral therapy
                          or specific immunomodulator therapy (other
                          than corticosteroids and IVIG).
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Recommended: PCP
                          prophylaxis. Allowed: 1. Immunoglobulin. 2.
                          Erythropoietin, G-CSF, and GM-CSF. 3.
                          Corticosteroids. 4. Ethionamide or isoniazid
                          for TB if no alternative is available. 5.
                          Pyridoxine (up to 50 mg/day) as vitamin
                          supplement.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of grade 3 or worse neuropathy /
                          lower motor neuronopathy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 07 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Ongoing drug or alcohol abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than 6
                          weeks of prior antiretroviral or
                          immunomodulator therapy. 2. Antiretroviral or
                          immunomodulator therapy within 7 days prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Chemotherapy
                          for active malignancy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Current grade 3 or worse neuropathy / lower
                          motor neuronopathy. 2. Other grade 3 or worse
                          clinical or laboratory toxicities. 3. Known
                          intolerance to either AZT or d4T.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0043  Stavudine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 d4T
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle Park, NC 27709
                          Contact: Mary Maha Elkins (919) 248-3294.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 5
                          Research Parkway Wallingford, CT 06492-7660
                          Contact: Dr Lisa Dunkle (203) 284-6903.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: BSA <= 1.11 m2: 180
                          mg/m2 (or placebo) q 6 hr for at least 52
                          weeks. BSA > 1.11: 200 mg (or placebo) q 6 hr
                          for at least 52 weeks. Drug 2: Weight < 40
                          kg: 1 mg/kg (or placebo) q 12 hr for at
                          leaweeks. Weight >= 40 kg: 40 mg (or placebo)
                          q 12 hr for at least 52 we
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Maximum 800 mg. Drug 2:
                          Maximum 80 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules
                          and 10 mg/ml strawberry-flavored syrup. Drug
                          2: Oral, 5 and 10 mg capsules and 1 mg/ml
                          powder for solu
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 52 weeks.
OTHER TREATMENT INFO.     END POINT: Drug-associated toxicity or
                          intolerance.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Missed a total
                          of 56 days of study drug. 2. Severe allergic
                          reaction or life-threatening toxicity. 3.
                          Development of aggressive Kaposi's sarcoma or
                          other malignancies requiring chemotherapy or
                          immunotherapy. 4. Patient noncompliance. 5.
                          At the request of the FDA, pharmaceutical
                          companies, IND sponsor, patient, parent or
                          guardian, or investigator.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 toxicity: Hold
                          study drug for up to 28 days; if toxicity has
                          resolved to grade 1 or 2, then resume study
                          drug at reduced dose. If toxicity remains at
                          grade 1 or 2 after 28 days at reduced dose,
                          then resume full dose. If grade 3 toxicity
                          recurs at full dose, hold study drug for up
                          to 28 days and then resume at permanent
                          reduced dose.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Burroughs Wellcome,
                          Bristol-Myers Squibb Company.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Stavudine/*ADVERSE EFFECTS
MESH HEADING              Zidovudine/*ADVERSE EFFECTS
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       3056-17-5 (Stavudine)
LAST REVISION DATE        941207
ENTRY MONTH               9403
ALABAMA                   University of Alabama at Birmingham School of
                          Medicine 751 CHT / University Station
                          Birmingham, AL 35294 Contact: Michael Cooney
                          (205) 939-9552 Contact: beeper (205) 869-9524
                          OPEN 940330 ACTU: 5046.
CALIFORNIA                Harbor General / UCLA Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 940513 ACTU: 3609.
CALIFORNIA                UCLA Medical Center / Pediatrics 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          940228 ACTU: 3601.
CALIFORNIA                Martin Luther King Jr / Drew Medical School /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 940502 ACTU: 3605.
CALIFORNIA                Long Beach Memorial Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 940602 ACTU: 3606.
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          940330 ACTU: 5048.
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 940418
                          ACTU: 4601.
CALIFORNIA                UCSF / Moffitt Hospital 602 / Pediatrics 505
                          Parnassus / Box 0105 San Francisco, CA
                          94143-0105 Contact: Debbie Trevithick (415)
                          476-6480 OPEN 940311 ACTU: 4501.
CALIFORNIA                Children's Hospital Oakland 747 Fifty Second
                          Street Oakland, CA 94609-1809 Contact: Jim
                          Riddel (510) 428-3000 X 282Contact: (510)
                          539-6311 X PagOPEN 940218 ACTU: 4504.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 940624 ACTU:
                          7001.
CONNECTICUT               Univ of Connecticut Farmington / Univ of CT
                          Health Center 263 Farmington Avenue
                          Farmington, CT 06032 Contact: Lorraine Wells
                          (203) 679-2320 OPEN 940721 ACTU: 7303.
CONNECTICUT               Yale University School of Medicine PO Box
                          3333 / 333 Cedar Street New Haven, CT
                          06510-8064 Contact: Unspecified (203)
                          737-4040 OPEN 940228 ACTU: 5038.
DISTRICT OF COLUMBIA      Children's National Medical Center / Special
                          Immuno Svc Suite 2108 / 111 Michigan Avenue
                          NW Washington, DC 20010-2970 Contact: Sandra
                          Jones (202) 884-3682 OPEN 940325 ACTU: 7101.
DISTRICT OF COLUMBIA      Howard University Hospital 2041 Georgia
                          Avenue NW Washington, DC 20060 Contact: Dr
                          Helga Finke (202) 865-1248 OPEN 940323 ACTU:
                          5044.
FLORIDA                   Northeast Florida AIDS Program / Div of
                          Pediatric Inf Dis/Im 653-1 W 8th Street
                          Jacksonville, FL 32209 Contact: Michelle
                          Eagle (904) 549-3051 OPEN 940823 ACTU: 5051.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 940608 ACTU: 4201.
GEORGIA                   Emory University Hospital 69 Butler Street SE
                          Atlanta, GA 30303 Contact: Judy Sarver (404)
                          616-6227 Contact: clinic (404) 616-4390
                          Contact: beeper (404) 899-5290 OPEN 940304
                          ACTU: 5030.
ILLINOIS                  University of Illinois at Chicago 840 S Wood
                          Street Chicago, IL 60612 Contact: Patricia
                          Naughton (312) 996-1778 OPEN 940504 ACTU:
                          5028.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 940210 ACTU: 4001.
ILLINOIS                  Cook County Hospital / Childrens Memorial
                          2300 Childrens Plaza Box #20 Chicago, IL
                          60614-3394 Contact: Debbie Fonken (312)
                          880-4757 OPEN 940406 ACTU: 4002.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 940311 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 940228 ACTU: 7201.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street / SHU-Main 3
                          Springfield, MA 01199 Contact: MaryPat Toye
                          (413) 784-5399 OPEN 940210 ACTU: 7302.
MASSACHUSETTS             University of Massachusetts Medical School /
                          Dept of Peds 55 Lake Avenue North Worcester,
                          MA 01655-0001 Contact: Joanne Shepard (508)
                          856-1692 OPEN 940516 ACTU: 7301.
MASSACHUSETTS             Children's Hospital 300 Longwood Avenue /
                          Carnegie 3 Boston, MA 02115 Contact: Robert
                          Bishop (617) 735-8198 OPEN 940210 ACTU: 2901.
MASSACHUSETTS             Boston City Hospital / Ped Infect Dis /
                          Finland Lab 774 Albany Street / Finland Lab
                          Room 301 Boston, MA 02118 Contact: Anne Marie
                          Reagan (617) 534-5813 OPEN 940304 ACTU: 2903.
MARYLAND                  University of Maryland School of Medicine /
                          Pediatrics 120 Penn Street Baltimore, MD
                          21201 Contact: Sue Lovelace (410) 706-8220
                          OPEN 940303 ACTU: 3702.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Charnell
                          Cromer (313) 745-5565 OPEN 940128 ACTU: 5041.
NORTH CAROLINA            University of North Carolina at Chapel Hill /
                          UNC CTU 516 Burnett Womack / CB# 7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-7883 OPEN 940323.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 940210 ACTU:
                          4701.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 940307 ACTU: 2801.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          Ninth Street Newark, NJ 07107-2198 Contact:
                          George Donavan McSherry (201) 268-8273 OPEN
                          940307 ACTU: 2803.
NEW JERSEY                Robert Wood Johnson University Hospital /
                          UMDNJ One Robert Wood Johnson Place CN19 New
                          Brunswick, NJ 08903-0019 Contact: Ida Kechula
                          (908) 937-7894 OPEN 940323 ACTU: 5032.
NEW YORK                  Beth Israel Medical Center / Pediatrics First
                          Avenue at 16th Street Dazian Pavilion Tenth
                          Floor New York, NY 10003 Contact: Ann Marshak
                          (212) 420-4432 OPEN 940303 ACTU: 4302.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue / Pediatric
                          New York, NY 10016 Contact: Nagamah Deygoo
                          (212) 263-6426 OPEN 940308 ACTU: 4401.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940228 ACTU:
                          4301.
NEW YORK                  Metropolitan Hospital Center / Pediatrics
                          Department 1901 First Avenue New York, NY
                          10029 Contact: Mavis Dummit (212) 230-7103
                          Contact: message machine (212) 230-6841
                          Contact: beeper (212) 537-1589 OPEN 940406
                          ACTU: 5003.
NEW YORK                  Incarnation Children's Ctr / c/o Columbia
                          Presb Med Ctr 142 Audubon Avenue New York, NY
                          10032 Contact: Pam Clark (212) 928-2228 OPEN
                          940228 ACTU: 4103.
NEW YORK                  The Columbia Presbyterian Medical Hosp
                          (Pediatric) 622 West 168th St Room 1161 New
                          York, NY 10032-3796 Contact: Kathy A Shea
                          (212) 305-7222 OPEN 940303 ACTU: 4101.
NEW YORK                  Harlem Hospital 506 Lenox Avenue New York, NY
                          10037 Contact: Rick Urbano (212) 939-4040
                          Contact: (212) 939-4045 OPEN 940218 ACTU:
                          5006.
NEW YORK                  Lincoln Hospital Center / Department of
                          Pediatrics 234 East 149th Street Bronx, NY
                          10451 Contact: Annie Villareal (718) 579-5329
                          Contact: (718) 579-5000 OPEN 940509 ACTU:
                          5004.
NEW YORK                  Bronx Lebanon Hospital Center / Department of
                          Pediatrics 1650 Selwyn Avenue Room 2C Bronx,
                          NY 10457 Contact: Patrice Edwards-Cihak (718)
                          960-1015 OPEN 940301 ACTU: 6901.
NEW YORK                  Westchester Hospital / New York Medical
                          College Munger Pavillion Room 134 Valhalla,
                          NY 10595 Contact: Liz Ahern (914) 285-7898
                          Contact: (914) 993-4643 OPEN 940228 ACTU:
                          5005.
NEW YORK                  North Shore University Hospital / Pediatric
                          Immunology 350 Community Drive Manhasset, NY
                          11030 Contact: Cathy Macco (516) 773-7676
                          OPEN 940513 ACTU: 5010.
NEW YORK                  King's County Hospital Center / SUNY HSCB 450
                          Clarkson Avenue Brooklyn, NY 11203 Contact:
                          Helen Bergin (718) 245-3342 Contact: (718)
                          245-3341 Contact: (718) 245-4485 OPEN 940228
                          ACTU: 5035.
NEW YORK                  SUNY at Brooklyn / Health Science Center /
                          Pediatrics 450 Clarkson Avenue / Box 24
                          Brooklyn, NY 11203 Contact: Barbara Driscoll
                          (718) 270-3081 OPEN 940210 ACTU: 5008.
NEW YORK                  SUNY Health Science Center at Stony Brook HSC
                          T 15 080 Stony Brook, NY 11794-8111 Contact:
                          Peggy Melendez (516) 444-1313 Contact: (516)
                          444-7692 Contact: beeper (516) 282-8808
                          Contact: Jeannie Conner (516) 444-2724 OPEN
                          940323 ACTU: 5040.
NEW YORK                  SUNY Health Science Center at Syracuse 750
                          East Adams Street Syracuse, NY 13210 Contact:
                          Kathie Shea-Contello (315) 464-6331 OPEN
                          940504 ACTU: 5039.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940311 ACTU: 1101.
OHIO                      Children's Hospital 700 Children's Drive
                          Columbus, OH 43205-2696 Contact: Jane Hunkler
                          (614) 722-4460 Contact: (614) 722-6050 OPEN
                          940308 ACTU: 2302.
OHIO                      Childrens Hospital of Cincinnati Eden and
                          Bethesda Avenue Cincinnati, OH 45267-0405
                          Contact: Jill Leonard (513) 558-6977 OPEN
                          940504 ACTU: 2404.
OTHER                     Ramon Ruiz Arnau University Hospital Laurel
                          Avenue Bayamon, PR 00619 Contact: Leticia
                          Diaz (809) 798-2733 OPEN 940317 ACTU: 5033.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 940311 ACTU: 5031.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          940308 ACTU: 6601.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 940502 ACTU: 6701.
PENNSYLVANIA              Saint Christopher's Hospital for Children /
                          Sect Imm & Rheum Erie Avenue at Front Street
                          Philadelphia, PA 19134-1095 Contact: Carole
                          Treston (215) 427-5284 Contact: FAX (215)
                          427-5555 OPEN 940301 ACTU: 6704.
RHODE ISLAND              Rhode Island Hospital / Brown University 593
                          Eddy Street Providence, RI 02903 Contact:
                          Cathy Kneut (401) 467-9884 OPEN 940608 ACTU:
                          5047.
SOUTH CAROLINA            Medical University of South Carolina Clinical
                          Science Building / 171 Ashley Avenue
                          Charleston, SC 29425-3312 Contact: Genny
                          Connelly (803) 792-2385 OPEN 940303 ACTU:
                          5037.
 
30
UNIQUE IDENTIFIER         NIH/00589
PROTOCOL ID NUMBERS       NIAID ACTG 239
PROTOCOL TITLE            A Phase I/II Study to Evaluate the Safety,
                          Toxicity, and Effect of Zidovudine Versus
                          Combination Therapy With Zidovudine and
                          Didanosine on CD4 Decline and Growth in Young
                          Infants With HIV Infection.
VERSION NUMBER & DATE     2 (940707)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Kovacs A
PROTOCOL CHAIRS           CO-CHAIR  Husson R
GENERAL DESCRIPTION       PURPOSE: To determine the pharmacokinetics,
                          safety, and efficacy of didanosine (ddI)
                          alone or in combination with zidovudine (AZT)
                          in HIV-infected infants.
GENERAL DESCRIPTION       RATIONALE: Early treatment of HIV-infected
                          infants with antiretroviral agents may
                          prevent the early and rapid decline of CD4
                          count and immunologic function. Combination
                          therapy may be preferred over monotherapy,
                          since resistance to a single agent can
                          develop rapidly. Currently, there is little
                          information on ddI monotherapy in young
                          infants less than 90 days and no information
                          on the use of combination therapy in this
                          population.
GENERAL DESCRIPTION       METHODOLOGY: In Part A, a cohort of patients
                          < 120 days of age receives open-label ddI
                          monotherapy for 1 week before initiation of
                          AZT/ddI combination therapy. After
                          pharmacokinetic data is obtained, an
                          additional cohort of patients receive ddI at
                          a higher dose. An age-adjusted dose for ddI
                          is determined for use in Part B. Part B
                          patients (< 180 days of age) are randomized,
                          on a double-blind basis, to receive AZT or
                          AZT/ddI. All patients continue treatment
                          until 12 months after the last patient on
                          Part B is enrolled.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection by
                          positive culture or DNA-PCR (neutralizable
                          p24 antigen also acceptable if age > 28
                          days), with confirmation by a second test.
                          NOTE: Cord blood is not acceptable. 2.
                          Asymptomatic infection with CD4 count <= 1750
                          cells/mm3 or < 30 percent OR symptomatic
                          infection (diagnosis of AIDS permitted).
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 35,208
STUDY DESIGN              Randomized; Pharmacokinetic; Drug Tolerance;
                          Drug Combination; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Combination and single drug therapy,
                          Combination and single pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 164 - 184 patients. (14-34
                          patients in Part A; 150 patients total in
                          Part B)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until 12 months
                          after last Part B patient is enrolled.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 8/164 - 184 (941207).
PROTOCOL DETAILS          STUDY DURATION: 2.5 - 3 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 24 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2.
                          Asymptomatic disease with CD4 count >= 1750
                          cells/mm3 or < 30 percent OR symptomatic
                          disease. NOTE: Per 07/07/94 amendment,
                          patients in Part A are < 120 days of age and
                          in Part B are < 180 days of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: > 24 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 1750 cells/mm3. or <
                          30 percent (asymptomatic patients only). ( 0
                          - 100 - 200 - 300 - 400 - 500 - 600 - 700 -
                          800 - plus).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.6 x ULN mg/dl. in the absence
                          of other unexplained causes (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN. in the absence of
                          other unexplained causes.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: WBC > 1500 cells/mm3. Neutrophils >
                          500 cells/mm3. Pancreatic amylase and lipase
                          < 2 x ULN.
PATIENT AGE               AGE: 01 Days - 06 Months.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Allowed: Recent
                          transfusions.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior vaccine
                          therapy.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Recommended: PCP
                          prophylaxis. Allowed: Acetaminophen if not on
                          a continual basis. NOTE: Drugs that are
                          metabolized by hepatic glucuronidation or
                          that are associated with occurrence of
                          pancreatitis are allowed but should be used
                          with caution.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          Pancreatitis at any time since birth. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded in Part B patients
                          only: More than 90 days of prior
                          antiretroviral or immunomodulator therapy,
                          exclusive of therapy received in utero.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Vaccine
                          therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Pancreatitis. 2. Clinically unstable
                          condition. 3. Current participation on a
                          vaccine trial.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 Videx
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle Park, NC 27709
                          Contact: Mary Maha Elkins (919) 248-3294.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 3 or 180 mg/m2 q 6
                          hr, depending on age. Drug 2: 25, 50, or 90
                          mg/m2 q 12 hr, depending on age
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 12 or 720 mg/m2. Drug
                          2: 50, 100, or 180 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 10 mg/ml syrup.
                          Drug 2: Oral, 10 or 20 mg/ml solution
OTHER TREATMENT INFO.     TREATMENT DURATION: Until 12 months after
                          last patient is enrolled.
OTHER TREATMENT INFO.     END POINT: Part A: Safety, toxicity, and
                          pharmacokinetic profile of ddI/AZT. Part B:
                          Long-term toxicity of AZT and AZT/ddI, CD4
                          count and growth differences.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Missed a total
                          of 56 days of study drug. 2. Severe allergic
                          reaction or life-threatening toxicity. 3.
                          Development of malignancies requiring
                          chemotherapy or immunotherapy. 4. Patient
                          noncompliance. 5. At request of FDA,
                          pharmaceutical companies, IND sponsor,
                          patient, parent, legal guardian, or
                          investigator.
OTHER TREATMENT INFO.     MODIFICATION: Doses are reduced or
                          discontinued for specific toxicities.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Didanosine/ADVERSE EFFECTS/*PHARMACOKINETICS/
                          THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*PHARMACOKINETICS/
                          THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9404
CALIFORNIA                Long Beach Memorial Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 941024 ACTU: 3606.
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          940401 ACTU: 5048.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 940506 ACTU:
                          7001.
DISTRICT OF COLUMBIA      Howard University Hospital 2041 Georgia
                          Avenue NW Washington, DC 20060 Contact: Dr
                          Helga Finke (202) 865-1248 OPEN 940405 ACTU:
                          5044.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 940504 ACTU: 4201.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 940426 ACTU: 4001.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 940919 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 940927 ACTU: 7201.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street / SHU-Main 3
                          Springfield, MA 01199 Contact: MaryPat Toye
                          (413) 784-5399 OPEN 940406 ACTU: 7302.
MASSACHUSETTS             Children's Hospital 300 Longwood Avenue /
                          Carnegie 3 Boston, MA 02115 Contact: Robert
                          Bishop (617) 735-8198 OPEN 940401 ACTU: 2901.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Charnell
                          Cromer (313) 745-5565 OPEN 941024 ACTU: 5041.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 940401 ACTU:
                          4701.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 940513 ACTU: 2801.
NEW JERSEY                Univ of Med & Dentistry of NJ / Univ Hospital
                          15 South Ninth Street Newark, NJ 07107-2198
                          Contact: George Donavan Mcsherry (201)
                          268-8273 OPEN 940406 ACTU: 2802.
NEW YORK                  Dr Dorothy Friedberg 310 Lexington Avenue New
                          York, NY 10016 Contact: Kathleen Farrell
                          (212) 263-6485 Contact: Dr Dorothy Friedberg
                          (212) 263-8473 OPEN 940624.
NEW YORK                  Incarnation Children's Ctr / c/o Columbia
                          Presb Med Ctr 142 Audubon Avenue New York, NY
                          10032 Contact: Pam Clark (212) 928-2228 OPEN
                          940502 ACTU: 4103.
NEW YORK                  The Columbia Presbyterian Medical Hosp
                          (Pediatric) 622 West 168th St Room 1161 New
                          York, NY 10032-3796 Contact: Kathy A Shea
                          (212) 305-7222 OPEN 940502 ACTU: 4101.
NEW YORK                  Bronx Lebanon Hospital Center / Department of
                          Pediatrics 1650 Selwyn Avenue Room 2C Bronx,
                          NY 10457 Contact: Patrice Edwards-Cihak (718)
                          960-1015 OPEN 940906 ACTU: 6901.
NEW YORK                  Children's Hospital at Albany Medical Center
                          22 New Scotland Avenue Albany, NY 12208
                          Contact: Mary Ellen Adams (518) 432-1501 OPEN
                          941005 ACTU: 5042.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 941130 ACTU: 1101.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 940610 ACTU: 5031.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          940706 ACTU: 6601.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 940912 ACTU: 6701.
SOUTH CAROLINA            Medical University of South Carolina Clinical
                          Science Building / 171 Ashley Avenue
                          Charleston, SC 29425-3312 Contact: Genny
                          Connelly (803) 792-2385 OPEN 940610 ACTU:
                          5037.
 
31
UNIQUE IDENTIFIER         NIH/00530
PROTOCOL ID NUMBERS       NIAID ACTG 238
PROTOCOL TITLE            A Prospective Study of Multidrug Resistance
                          and a Pilot Study of the Safety of and
                          Clinical and Microbiologic Response to
                          Levofloxacin in Combination With Other
                          Antimycobacterial Drugs for Treatment of
                          Multidrug-Resistant Pulmonary Tuberculosis
                          (MDRTB) in HIV-Infected Patients.
VERSION NUMBER & DATE     6 (940928)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Epidemiology
GENERAL DESCRIPTION       PURPOSE: To determine the demographic,
                          behavioral, clinical, and geographic risk
                          factors associated with the occurrence of
                          multi-drug resistant pulmonary tuberculosis
                          (MDRTB). To evaluate the clinical and
                          microbiological responses and overall
                          survival of MDRTB patients who are treated
                          with levofloxacin-containing multiple-drug
                          regimens chosen from a hierarchical list. Per
                          9/28/94 amendment, to assess whether
                          persistent or recurrent positive sputum
                          cultures of patients who show failure or
                          relapse are due to the same strain or
                          reinfection with a new strain.
GENERAL DESCRIPTION       RATIONALE: Among TB patients, there has been
                          an increase in progressive disease due to the
                          emergence of antimycobacterial drug-resistant
                          strains of Mycobacterium tuberculosis.
                          Failure to identify patients at high risk for
                          MDRTB increases the hazard for both treatment
                          failure and development of resistance to
                          additional therapeutic agents. Efforts to
                          improve survival in patients with MDRTB will
                          depend on improved methods of assessing the
                          risk of acquisition of MDRTB and identifying
                          drug susceptibility patterns in a timely
                          fashion.
GENERAL DESCRIPTION       METHODOLOGY: Patients are asked a series of
                          questions to determine epidemiologic factors
                          that may be predictive of MDRTB. Patients who
                          are determined to be at low risk for MDRTB
                          will be referred to another TB treatment
                          protocol (ACTG 222), if appropriate. Patients
                          suspected of having primary or acquired MDRTB
                          or those with confirmed MDRTB will be offered
                          a regimen of anti-TB therapy from a
                          hierarchically ordered list of drugs, based
                          on the patient's resistance status (suspect
                          primary MDRTB, suspect acquired MDRTB, or
                          confirmed MDRTB). The hierarchical list is as
                          follows: isoniazid, rifampin, ethambutol,
                          streptomycin, levofloxacin, ethionamide,
                          cycloserine, capreomycin, aminosalicylic
                          acid, and clofazimine. Treatment will be
                          administered daily for at least 6 months,
                          then on an intermittent schedule at the
                          clinician's discretion. Patients with
                          confirmed MDRTB (defined as known resistance
                          to at least isoniazid and rifampin within 6
                          months prior to study entry) will receive a
                          minimum of 18 months of treatment following
                          sputum culture conversion. Follow-up is
                          performed every 4 weeks for 8 weeks, and then
                          every 8 weeks.
PROTOCOL PHASE            Epidemiology / Treatment Pilot
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Tuberculosis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions. EPIDEMIOLOGIC AND TREATMENT
                          PILOT: 1. Working diagnosis of HIV infection
                          based on medical history, behavioral history,
                          clinical signs and symptoms, and laboratory
                          tests. 2. Working diagnosis of pulmonary TB.
                          Per 08/02/94 amendment, patients with
                          confirmed MDRTB at baseline are not eligible
                          for the epidemiologic study only. TREATMENT
                          PILOT ONLY: 1. Positive sputum AFB smear (or
                          a positive sputum culture for TB within 6
                          months prior to study entry). NOTE:
                          Extrapulmonary TB is permitted. 2. Assessment
                          of suspect primary, suspect acquired, AND/OR
                          confirmed MDRTB. (Patients are NOT eligible
                          if they are at low risk for MDRTB, i.e., have
                          no risk factors for either primary or
                          acquired MDRTB, or if they have confirmed
                          pansusceptibility or monoresistance for the
                          present episode to isoniazid or rifampin.)
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    CPCRA 026. IND 42,796
STUDY DESIGN              Prospective; Multicenter; Drug Combination;
                          Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Epidemiology, Comparative drug
                          therapy, Combination drug therapy, Drug
                          efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 525 patients. (525
                          patients for epidemiologic portion; 30
                          patients with confirmed MDRTB for treatment
                          pilot)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 - 4.5 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 50/525 (941207).
PROTOCOL DETAILS          STUDY DURATION: Until 3 years following
                          enrollment of last patient.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 21 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Working diagnosis of HIV infection.
                          2. Working diagnosis of pulmonary TB. Per
                          08/02/94 amendment, patients with confirmed
                          MDRTB at baseline are not eligible for the
                          epidemiologic study only. FOR TREATMENT
                          PILOT: 1. Positive sputum AFB smear (or a
                          positive sputum culture for TB within 6
                          months prior to study entry). 2. Assessment
                          of suspect primary, suspect acquired, AND/OR
                          confirmed MDRTB. 3. Life expectancy of at
                          least 2 weeks. 4. Age >= 18 years for suspect
                          MDRTB. Age >= 13 years for confirmed MDRTB.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 5 x ULN mg/dl. (ULN = upper
                          limit of normal). (Treatment pilot patients).
PATIENT INCLUSION CRIT.   CREATININE: <= 3 x ULN. (Treatment pilot
                          patients).
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant (except
                          patients with confirmed MDRTB).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant (except
                          patients with confirmed MDRTB).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: More than 6 weeks
                          total therapy within 3 months prior to study
                          entry using three or more drugs effective
                          against the isolates. (Per 08/02/94
                          amendment, patients from protocol ACTG
                          222/CPCRA 019 who have MDRTB are eligible for
                          rollover to this study regardless of
                          treatment duration on ACTG 222/CPCRA 019).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          hypersensitivity or resistance to quinolones.
                          2. Other disorders or conditions for which
                          the study drugs are contraindicated.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0112  Amikacin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0199  Capreomycin sulfate
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0067  Clofazimine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0195  Cycloserine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0111  Ethambutol
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0196  Ethionamide
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0123  Isoniazid
SUBSTANCE IDENTIFICATION  Drug 8  DRG-0129  Levofloxacin
SUBSTANCE IDENTIFICATION  Drug 9  DRG-0200  Aminosalicylic acid
SUBSTANCE IDENTIFICATION  Drug 10: DRG-012  Pyrazinamide
SUBSTANCE IDENTIFICATION  Drug 11: DRG-012  Pyridoxine
SUBSTANCE IDENTIFICATION  Drug 12: DRG-010  Rifampin
SUBSTANCE IDENTIFICATION  Drug 13: DRG-020  Streptomycin sulfate
MANUFACTURERS             Drug 1: Bristol-Myers Squibb Company PO Box
                          4500 Princeton, NJ 08543-4500 Contact: Drug
                          Information Department (800) 321-1335.
MANUFACTURERS             Drug 2: Eli Lilly and Company 307 East
                          McCarty Street Indianapolis, IN 46285
                          Contact: Medical Department (800) 545-5979.
MANUFACTURERS             Drug 3: Ciba Pharmaceutical Company 556
                          Morris Avenue Summit, NJ 07901 Contact:
                          Medical Services Department (908) 277-5000.
MANUFACTURERS             Drug 4: Eli Lilly and Company 307 East
                          McCarty Street Indianapolis, IN 46285
                          Contact: Medical Department (800) 545-5979.
MANUFACTURERS             Drug 5: Lederle Laboratories Professional
                          Services Department Pearl River, NY 10965
                          Contact: Professional Services (914)
                          735-2815.
MANUFACTURERS             Drug 6: Wyeth-Ayerst Laboratories PO Box 8299
                          Philadelphia, PA 19101 Contact: General
                          Information (610) 688-4400.
MANUFACTURERS             Drug 7: Danbury Pharmacal 131 West Street
                          Danbury, CT 06810 Contact: General
                          Information (203) 744-7200.
MANUFACTURERS             Drug 8: Ortho Pharmaceutical Corporation
                          Route 202 / PO Box 300 Raritan, NJ 08869-0602
                          Contact: Medical Inquiries (800) 682-6532.
MANUFACTURERS             Drug 9: Jacobus Pharmaceutical Company PO Box
                          5290 / 37 Cleveland Lane Princeton, NJ 08540
                          Contact: Professional Services (609)
                          921-7447.
MANUFACTURERS             Drug 10: Lederle Laboratories Professional
                          Services Department Pearl River, NY 10965
                          Contact: Professional Services (914)
                          735-2815.
MANUFACTURERS             Drug 11: Tishcon Corporation 30 New York
                          Avenue Westbury, NY 11590 Contact:
                          Unspecified (516) 333-3050.
MANUFACTURERS             Drug 12: Marion Merrell Dow Medical
                          Information / PO Box 9627 Kansas City, MO
                          64134-0627 Contact: Medical Information (800)
                          633-1610.
MANUFACTURERS             Drug 13: Pfizer Incorporated / Roerig
                          Division 235 East 42nd Street New York, NY
                          10017-7851 Contact: Professional Information
                          (212) 573-2187.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 15 mg/kg daily (only
                          in patients whose isolates are resistant to
                          streptomycin sulfate). Drug 2: 15 mg/kg
                          daily. Drug 3: 100 - 200 mg daily. Drug 4:
                          0.5 - 1 g daily (given in doses of 250 mg BID
                          or QID). Drug 5: 25 mg/kg daily or 25-30
                          mg/kg TIW (50 percent dose in patients with
                          creatinine clearance < 50 ml/min; 25 percent
                          dosethose with creatinine clearance < 10
                          ml/min). Drug 6: 0.5 - 1.0 g daily (given in
                          doses of 250 mg BID or QID)Drug 7: 300 mg
                          daily (600 mg daily at discretion of
                          physician).Drug 8: 500 mg BID (50 percent
                          dose in patients with creatinineclearance
                          20-50 ml/min). Drug 9: 4 g TID. Drug 10: 25
                          mg/kg daily or 50-70 mg/kg TIW, not to exceed
                          2.5 ggiven TIW. Drug 11: Administered with
                          isoniazid. Drug 12: 600 mg daily. Drug 13: 15
                          mg/kg daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 15 mg/kg. Drug 2: 15
                          mg/kg. Drug 3: 100 - 200 mg. Drug 4: 0.5 - 1
                          g. Drug 5: 25 mg (if given daily). Drug 6:
                          0.5 - 1.0 g. Drug 7: 300 mg (600 mg at
                          discretion of physician). Drug 8: 1000 mg (50
                          percent dose in patients with creatinine
                          clearance 20-50 ml/min). Drug 9: 12 g. Drug
                          10: 25 mg/kg (if given daily). Drug 12: 600
                          mg. Drug 13: 15 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intramuscular (IM) or
                          intravenous (IV), 500 mg vials. Drug 2:
                          Intramuscular (IM) or intravenous (IV); 1 g
                          vials. Drug 3: Oral, 100 mg capsules. Drug 4:
                          Oral, 250 capsules. Drug 5: Oral, 400 mg
                          tablets. Drug 6: Oral, 250 mg tablets. Drug
                          7: Oral, 300 mg tablets. Drug 8: Oral and
                          intravenous; 125 and 500 mg tablets, 25 mg/ml
                          Drug 9: Oral, 4 g packets. Drug 10: Oral, 500
                          mg tablets. Drug 11: Oral, 50 mg tablets.
                          Drug 12: Oral, 150 and 300 mg tablets. Drug
                          13: Intramuscular (IM) or intravenous (IV); 1
                          g vials
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 6 months.
OTHER TREATMENT INFO.     END POINT: Epidemiologic outcome measure:
                          Drug susceptibility results of baseline
                          sputum cultures. Treatment pilot: Survival,
                          time to defervescence, weight change, time to
                          sputum smear and culture conversion,
                          treatment response, toxicity, and strain
                          variation.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          permanently for the following reasons: 1.
                          Found not to have MDRTB or HIV infection. 2.
                          Not in the best interest of patient to
                          continue. 3. Patient refusal to receive
                          further therapy. 4. Termination of study.
                          Patients discontinue treatment temporarily
                          for the following reasons: 1. Unacceptable
                          toxicity that resolves. 2. Development of
                          acute opportunistic infection, acute
                          bacterial infection, or malignancy.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 or 4 toxicity in
                          the first 8-12 weeks of therapy: Hold drug or
                          drugs most likely to be associated with the
                          particular toxicity. For recurrent grade 3 or
                          4 toxicity, discontinue the drug permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), National Institute of
                          Allergy & Infectious Diseases (CPCRA).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Amikacin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Aminosalicylic Acids/ADVERSE EFFECTS/
                          *THERAPEUTIC USE
MESH HEADING              Capreomycin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Clofazimine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Cycloserine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Resistance, Microbial
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Ethionamide/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Isoniazid/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Ofloxacin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Opportunistic Infections/COMPLICATIONS/DRUG
                          THERAPY/*EPIDEMIOLOGY
MESH HEADING              Pyrazinamide/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Pyridoxine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Rifampin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Streptomycin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Tuberculosis, Pulmonary/COMPLICATIONS/DRUG
                          THERAPY/*EPIDEMIOLOGY
MESH HEADING              p-Aminosalicylic Acid/ADVERSE EFFECTS/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Aminosalicylic Acids)
CAS REGISTRY NUMBER       11003-38-6 (Capreomycin)
CAS REGISTRY NUMBER       13292-46-1 (Rifampin)
CAS REGISTRY NUMBER       2030-63-9 (Clofazimine)
CAS REGISTRY NUMBER       37517-28-5 (Amikacin)
CAS REGISTRY NUMBER       536-33-4 (Ethionamide)
CAS REGISTRY NUMBER       54-85-3 (Isoniazid)
CAS REGISTRY NUMBER       57-92-1 (Streptomycin)
CAS REGISTRY NUMBER       65-23-6 (Pyridoxine)
CAS REGISTRY NUMBER       65-49-6 (p-Aminosalicylic Acid)
CAS REGISTRY NUMBER       68-41-7 (Cycloserine)
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       82419-36-1 (Ofloxacin)
CAS REGISTRY NUMBER       98-96-4 (Pyrazinamide)
LAST REVISION DATE        941207
ENTRY MONTH               9403
ILLINOIS                  Cook County Hospital Passavant Pavilion /
                          Room 823 / 303 East Superior Chicago, IL
                          60611 Contact: Baiba L Berzins (312) 908-9636
                          OPEN 940829 ACTU: 2705.
MICHIGAN                  Henry Ford Hospital 2799 West Grand Boulevard
                          Detroit, MI 48202 Contact: Diane Mastro-Polak
                          (313) 876-7664 OPEN 940427.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 940210 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 940317 ACTU: 0401.
NEW YORK                  St Clare's Hospital and Health Center 415
                          West 51st Street New York, NY 10019 Contact:
                          Phyllis Ristau (212) 459-8449 OPEN 940225
                          ACTU: 2204.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          940204 ACTU: 2201.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940627 ACTU: 1801.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 940606 ACTU: 7501.
NEW YORK                  Harlem AIDS Treatment Group Harlem Hospital /
                          Women's Pavilion Room 126 New York, NY 10037
                          Contact: Joshua Standig (212) 939-2951 OPEN
                          940203.
NEW YORK                  Bronx-Lebanon Hospital Center 1309 Fulton
                          Avenue Bronx, NY 10456 Contact: Cathy Pollard
                          (718) 293-2593 Contact: (718) 901-8916 OPEN
                          940204.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 940228 ACTU:
                          1905.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940228
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940228
                          ACTU: 1904.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940228 ACTU: 1903.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940204 ACTU: 1901.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940204
                          ACTU: 1902.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940228 ACTU: 1906.
NEW YORK                  North Central Bronx Hospital / Samaritan
                          Village Inc 418 Forchheimer ID / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940228 ACTU: 1907.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 940204
                          ACTU: 5901.
NEW YORK                  Interfaith Medical Ctr / SUNY Brooklyn Health
                          Sciences Ctr ACTU Box 77 / 450 Clarkson
                          Avenue Brooklyn, NY 11203-2098 Contact:
                          Donald Smith (718) 270-3372 Contact: (718)
                          270-3370 OPEN 940325 ACTU: 5902.
NEW YORK                  Clinical Directors Network of Region II 5601
                          2nd Avenue #3 Brooklyn, NY 11220 Contact:
                          Linda Podhurst (212) 255-3841 OPEN 940204.
 
32
UNIQUE IDENTIFIER         NIH/00590
PROTOCOL ID NUMBERS       NIAID ACTG 237
PROTOCOL TITLE            Phase II Randomized Open-Label Trial of
                          Atovaquone Plus Pyrimethamine and Atovaquone
                          Plus Sulfadiazine for the Treatment of Acute
                          Toxoplasmic Encephalitis.
VERSION NUMBER & DATE     2 (940603)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy, safety,
                          and tolerance of atovaquone with either
                          pyrimethamine or sulfadiazine in AIDS
                          patients with toxoplasmic encephalitis.
GENERAL DESCRIPTION       RATIONALE: AIDS patients with toxoplasmic
                          encephalitis who receive the standard therapy
                          combination of sulfadiazine and pyrimethamine
                          experience a high frequency of severe
                          toxicity. Atovaquone, an antibiotic that has
                          demonstrated efficacy against toxoplasmosis
                          in animal models and in preclinical testing
                          has been well tolerated, is now available as
                          a suspension, which is more readily absorbed
                          than the tablet form of the drug. The
                          efficacy and safety of atovaquone in
                          combination with sulfadiazine or
                          pyrimethamine will be studied.
GENERAL DESCRIPTION       METHODOLOGY: Seventy patients are randomized
                          to receive atovaquone with either
                          pyrimethamine or sulfadiazine for up to 48
                          weeks. Additionally, three cohorts of 10
                          patients each who have a history of
                          treatment-limiting toxicity to pyrimethamine,
                          sulfadiazine, or both drugs receive
                          atovaquone plus the alternate drug or
                          atovaquone plus clarithromycin. All patients
                          receiving pyrimethamine also receive
                          leucovorin protection.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Toxoplasmic encephalitis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA (confirmed by Western blot), serum p24
                          antigen, or HIV culture OR prior diagnosis of
                          AIDS by CDC definition (other than CD4 count
                          < 200 cells/mm3). 2. Definitive, presumptive,
                          or relapsed toxoplasmic encephalitis
                          (progression of lesions or appearance of new
                          lesions).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    ANRS 039. IND 44,387
STUDY DESIGN              Randomized; Open Label; 2-Arm;
                          Noncomparative; Drug Tolerance; Drug
                          Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 56 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 8/100 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 25 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection or
                          diagnosis of AIDS (except for CD4 count < 200
                          cells/mm3). 2. Toxoplasmic encephalitis.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7 g/dl. (Transfusion
                          permitted).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 70 ml/min. (if
                          creatinine value not available).
PATIENT INCLUSION CRIT.   KARNOFSKY: > 30.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Aerosolized
                          pentamidine for PCP prophylaxis.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of treatment-limiting toxicity to
                          atovaquone. 2. Receipt of > 72 hours of
                          treatment prior to study entry for the
                          current episode of toxoplasmic encephalitis.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Trimethoprim-sulfamethoxazole. 2. Primaquine.
                          3. Sulfonamides. 4. Antifolates. 5. Dapsone.
                          6. Clarithromycin (except for patients in the
                          cohort to receive this drug). 7.
                          Azithromycin. 8. Clindamycin. 9. Other
                          macrolides. 10. Gamma interferon. 11.
                          Metoclopramide. 12. G-CSF or GM-CSF. Excluded
                          in patients receiving clarithromycin as study
                          drug: Terfenadine, astemizole, or any other
                          long-acting, non-sedating antihistamines.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Coma.
                          2. Opportunistic infection that requires
                          either acute or maintenance treatment with
                          disallowed medications. 3. Any infections or
                          neoplasms of the central nervous system other
                          than Toxoplasma, HIV encephalopathy, or
                          syphilis. 4. Unable to take oral study drugs.
                          5. Malabsorption (i.e., three or more
                          episodes of diarrhea per day that has caused
                          >= 10 percent loss of body weight over the
                          past 4 weeks). 6. Positive CSF for
                          Cryptococcus antigen or culture. 7.
                          Malignancy requiring use of cytotoxic
                          chemotherapy. 8. Medical or social condition
                          that would adversely affect study
                          participation or compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0084  Atovaquone
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0027  Pyrimethamine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0002  Leucovorin calcium
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0099  Clarithromycin
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0214  Sulfadiazine
TRADE NAME OF SUBSTANCE   Drug 2 Daraprim
TRADE NAME OF SUBSTANCE   Drug 3 Wellcovorin
TRADE NAME OF SUBSTANCE   Drug 4 Biaxin
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 3: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 4: Abbott Laboratories One Abbott Park
                          Road / Department 422 Abbott Park, IL
                          60064-3500 Contact: Medical Services (708)
                          938-0601.
MANUFACTURERS             Drug 5: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1500 mg BID for 6
                          weeks, with possible extension for
                          anadditional 42 weeks. Drug 2: 200 mg on day
                          1, followed by 50 or 75 mg (depending on
                          weight) daily for 6 weeks, with possible
                          extension for an addit42 weeks. Drug 3: 10 mg
                          daily administered with pyrimethamine. Drug
                          4: 500 mg BID for 6 weeks, with possible
                          extension for an additional 42 weeks. Drug 5:
                          1000 or 1500 mg (depending on weight) QID for
                          6 weeks, possible extension for an additional
                          42 weeks at 1000 or 1500 mBID
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 3000 mg. Drug 2: 200 mg
                          on day 1, then 50 or 75 mg. Drug 3: 10 mg.
                          Drug 4: 1000 mg. Drug 5: 4000 or 6000 mg (for
                          first 6 weeks), then 2000 or 3000 (for 42
                          weeks)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, micronized
                          suspension (150 mg/ml) in 120 ml bottles.
                          Drug 2: Oral, 25 mg scored tablets. Drug 3:
                          Oral, 5 mg tablets. Drug 4: Oral, 500 mg
                          tablets. Drug 5: Oral, 500 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 48 weeks.
OTHER TREATMENT INFO.     END POINT: Clinical response (quantifiable
                          neurologic exam); radiologic response (CT or
                          MRI).
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Negative
                          Toxoplasma serology. 2. Brain biopsy or
                          aspirate positive for an etiology other than
                          toxoplasmosis. 3. Therapeutic failure on
                          clinical or radiographic evaluation. 4.
                          Unacceptable toxicity. 5. Requirement for
                          therapy with a prohibited drug. 6. Pregnancy.
                          7. Development of malabsorption syndrome. 8.
                          Currently receiving a rifamycin and has
                          documented low plasma levels of atovaquone
                          defined as <= 7 mcg/ml. 9. Considered in best
                          interest of patient to withdraw from study or
                          desire of patient to withdraw.
OTHER TREATMENT INFO.     MODIFICATION: Dose is held for specific
                          toxicities.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Clarithromycin/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Encephalitis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Leucovorin/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Middle Age
MESH HEADING              Naphthoquinones/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Pyrimethamine/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Sulfadiazine/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Toxoplasmosis, Cerebral/COMPLICATIONS/*DRUG
                          THERAPY
CAS REGISTRY NUMBER       58-05-9 (Leucovorin)
CAS REGISTRY NUMBER       58-14-0 (Pyrimethamine)
CAS REGISTRY NUMBER       68-35-9 (Sulfadiazine)
CAS REGISTRY NUMBER       81103-11-9 (Clarithromycin)
CAS REGISTRY NUMBER       94015-53-9 (atovaquone)
LAST REVISION DATE        941207
ENTRY MONTH               9408
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 940720
                          ACTU: 0901.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 940922
                          ACTU: 5201.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940907 ACTU: 2701.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940718 ACTU: 2601.
INDIANA                   Methodist Hospital Of Indiana 550 North
                          University Boulevard Room 5550 Indianapolis,
                          IN 46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 941114 ACTU: 2602.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 940902 ACTU: 0201.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940822 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 940822
                          ACTU: 2102.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 940817 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 940822 ACTU: 0401.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 941013 ACTU: 7502.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940718
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940718 ACTU: 1901.
NEW YORK                  Bronx Veterans Administration Medical Center
                          130 West Kingsbridge Road Bronx, NY 10468
                          Contact: Nancy Ostrow (718) 584-9000 X
                          667Contact: (718) 584-9000 X 667OPEN 941014
                          ACTU: 1804.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 940728
                          ACTU: 5901.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 940822 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941006 ACTU: 1102.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 940824
                          ACTU: 2301.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 941101 ACTU:
                          2401.
OTHER                     Hopital Cochin 46 Rue Henri Huchard Paris, FR
                          Contact: Sophie Puget (331)402-5889 0 OPEN
                          940916 ACTU: 8703.
OTHER                     Hopital Bichat-Claude Bernard 46 rue Henri
                          Huchard Paris cedex 8, FR Contact: Sophie
                          Puget (331)402-5889 0 OPEN 940916 ACTU: 8713.
OTHER                     Hopital Hotel-Dieu 46 Rue Henri Huchard Paris
                          Cedex 8, FR BP 1005 Contact: Sophie Puget
                          (331)402-5889 0 OPEN 940916 ACTU: 8714.
OTHER                     Hopital Jean Verdier 46 Rue Henri Huchard
                          Paris Cedex 8, FR Contact: Sophie Puget
                          (331)402-5889 0 OPEN 940920 ACTU: 8712.
OTHER                     Hopital Pateur / Infectious Diseases Unit 46
                          Rue Henri Huchard Paris Cedex 8, FR Contact:
                          Sophie Puget (331)402-5889 0 OPEN 940916
                          ACTU: 8716.
OTHER                     Hopital Saint-Andre 46 Rue Henri Huchard
                          Paris Cedex 8, FR Contact: Sophie Puget
                          (331)402-5889 0 OPEN 940916 ACTU: 8715.
 
33
UNIQUE IDENTIFIER         NIH/00487
PROTOCOL ID NUMBERS       NIAID ACTG 236
PROTOCOL TITLE            Safety and Efficacy of Polyethylene
                          Glycolated IL-2 (PEG IL-2) Plus Zidovudine
                          and Thymosin alpha 1 in HIV-Positive,
                          Asymptomatic and Symptomatic Individuals.
VERSION NUMBER & DATE     (921201)
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Merigan TC
GENERAL DESCRIPTION       PURPOSE: To determine the safety of thymosin
                          alpha 1 given twice weekly in a regimen of
                          daily oral zidovudine (AZT) and biweekly
                          polyethylene glycolated interleukin-2 (PEG
                          IL-2). To determine the effect of thymosin
                          alpha 1 and PEG IL-2 in combination with AZT
                          on immunologic and pharmacokinetic markers.
GENERAL DESCRIPTION       RATIONALE: AIDS is characterized by
                          diminished T helper cell number and function.
                          Thymosin alpha 1 appears to both increase
                          IL-2 receptors on lymphocytes in vitro and
                          enhance lymphocyte maturation in vivo; thus,
                          the drug may further enhance the CD4 T cell
                          levels in patients receiving AZT and PEG
                          IL-2.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stabilized on oral
                          AZT (500 mg) daily for 8 weeks and then begin
                          receiving bolus infusions of PEG IL-2 (1
                          million IU/m2) every other week for at least
                          four doses. Thymosin alpha 1 is then added to
                          this regimen at a dose of 0.4 mg SC twice
                          weekly for 4 weeks. If no significant
                          toxicity occurs, thymosin alpha 1 is
                          increased to 1.6 mg and administered along
                          with scheduled doses of PEG IL-2 for an
                          additional 8 weeks.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive confirmed by
                          Western blot (or immunofluorescence) at
                          Stanford Hospital. 2. CD4 lymphocyte count >
                          50 and < 200 cells/mm3 within 2 weeks of
                          study entry. 3. No active opportunistic
                          infections.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Drug Combination; Drug Tolerance;
                          Pharmacokinetic; Dose Escalating
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Pharmacokinetics,
                          Immunology, Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 12 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 13/12 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. CD4 count >
                          50 and < 200 cells/mm3. 3. No active
                          opportunistic infections. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 30 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10 g/dl. (No transfusion in
                          previous month).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 50 < 200 cells/mm3. (
                          100 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 1.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 90.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Prophylactic
                          pentamidine for Pneumocystis carinii.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: 1. Transfusion
                          within 4 weeks prior to study entry. 2.
                          Radiation within 30 days prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Known anti-HIV
                          medication (other than AZT) or known
                          immunomodulators (e.g., systemic steroids,
                          interferons, interleukins) or other
                          chemotherapy within 30 days prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antihypertensive medication other than
                          diuretics. 2. Chemotherapy, hormonal therapy,
                          or other immunotherapy. 3. Other
                          investigational drugs, agents, or devices. 4.
                          Beta-blockers. 5. Non-topical steroids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Concurrent neoplasms other than basal cell
                          carcinoma of the skin, in situ carcinoma of
                          the cervix, or Kaposi's sarcoma. 2.
                          Significant cardiac disease or CNS lesions or
                          other neurologic abnormalities. 3. Score of >
                          0.5 on ACTG AIDS Dementia Complex staging. 4.
                          Major organ allograft. 5. Intolerance to AZT
                          at 500 mg/day.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0165  Thymosin alpha 1
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0093  Polyethylene Glycolated
                          IL-2
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Alpha I Biomedicals / Viral
                          Technologies Inc 6903 Rockledge Drive / Suite
                          1200 Bethesda, MD 20817 Contact: Dr Vincent
                          Simmon (301) 564-4400.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 3: Cetus Corporation 1400 Fifty-Third
                          Street Emeryville, CA 94608 Contact: Dr Gwen
                          Fyfe (510) 601-3169.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 0.4 mg/m2 twice
                          weekly for 4 weeks, then 1.6 mg/m2 twicweekly
                          for 8 weeks. Drug 2: 100 mg 5 times daily.
                          Drug 3: 1 million IU/m2 over 30 min q other
                          week for 20 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 2: 500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous. Drug 2:
                          Oral. Drug 3: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 20 weeks.
OTHER TREATMENT INFO.     END POINT: Toxicity, clinical improvement,
                          enhanced immune response.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Grade 4
                          toxicity of any type. 2. Significant adverse
                          effects or major organ toxicities associated
                          with PEG IL-2. 3. Two consecutive occurrences
                          of previously undetectable viral growth after
                          the first dose of PEG IL-2. 4. Intolerance to
                          500 mg AZT daily. 5. Disease progression or a
                          new occurrence or recurrence of an
                          AIDS-defining illness. 6. Need for treatment
                          with another drug that would potentiate the
                          toxicity of the study drugs or would have an
                          antiretroviral effect.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 toxicity (other
                          than anemia): Hold thymosin alpha 1 until
                          toxicity resolves, then resume at 50 percent
                          dose at the investigator's discretion.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY/IMMUNOLOGY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Interleukin-2/*ADVERSE EFFECTS/IMMUNOLOGY/
                          THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Polyethylene Glycols
MESH HEADING              T-Lymphocytes/IMMUNOLOGY
MESH HEADING              Thymosin/ANALOGS & DERIVATIVES/*ADVERSE
                          EFFECTS/IMMUNOLOGY/THERAPEUTIC USE
MESH HEADING              Zidovudine/*ADVERSE EFFECTS/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Interleukin-2)
CAS REGISTRY NUMBER       0 (Polyethylene Glycols)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69521-94-4 (thymosin alpha(1))
LAST REVISION DATE        941207
ENTRY MONTH               9303
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 930303
                          ACTU: 0501.
 
34
UNIQUE IDENTIFIER         NIH/00505
PROTOCOL ID NUMBERS       NIAID ACTG 235
PROTOCOL TITLE            Active Immunization of HIV-1 Infected,
                          Pregnant Women With CD4 Lymphocyte Counts >=
                          400/mm3: A Phase I Study of Safety and
                          Immunogenicity of MN rgp120/HIV-1 Vaccine
                          (NOTE: Some Patients Receive Placebo).
VERSION NUMBER & DATE     (940601)
TRIAL CATEGORY            Vaccines
TRIAL CATEGORY            Pregnancy
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Wara DW
PROTOCOL CHAIRS           CO-CHAIR  Lambert JS, Wright PF
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of
                          rgp120/HIV-1MN vaccine in HIV-1 infected
                          pregnant women with CD4 counts >= 400
                          cells/mm3. To evaluate the immunogenicity of
                          this vaccine in pregnant women and the
                          passive acquisition of vaccine-specific
                          antibody in their infants. To evaluate the
                          induction or augmentation by rgp120/HIV-1MN
                          vaccine of mucosal immune response in the
                          gastrointestinal and reproductive tracts
                          during pregnancy. To isolate and genetically
                          characterize the HIV-1 present in
                          cervicovaginal fluid specimens of pregnant
                          women and compare it to that present in their
                          peripheral blood mononuclear cells and to
                          that of their infected infants.
GENERAL DESCRIPTION       RATIONALE: Evidence suggests that an advanced
                          stage of disease with high plasma viremia is
                          associated with increased transmission of
                          HIV-1 to the fetus. Slowing the progression
                          of disease, reducing the titer of virus in
                          plasma, and increasing the titer of
                          epitope-specific antibody are potentially
                          attainable goals through active immunization
                          of the mother during pregnancy.
GENERAL DESCRIPTION       METHODOLOGY: Pregnant women are randomized to
                          receive an initial injection of MN rgp120
                          vaccine or alum placebo between week 16 and
                          week 24 of gestation, followed by monthly
                          booster injections concluding at the end of
                          pregnancy, for a total of five injections.
                          Patients may have optional booster
                          immunizations (vaccine or placebo) at 3, 6,
                          9, and 12 months after delivery. Mothers and
                          infants are followed through 18 months after
                          delivery. Per 06/94 addendum, patients will
                          be contacted once or twice per year for at
                          least 5 years to check on health status of
                          patient and child.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 infection documented by
                          ELISA and another confirmatory test such as
                          Western blot or culture. 2. CD4 count >= 400
                          cells/mm3. 3. No AIDS-defining illness or
                          other systemic manifestations related to HIV
                          (other than generalized lymphadenopathy). 4.
                          HIV p24 < 30 pg/ml. 5. Proven pregnancy in
                          the 16th to 24th week of gestation at study
                          entry, with no special obstetrical risks. 6.
                          Concurrent AZT therapy is permitted.
ELIGIBILITY               ASYM. PGL.
OTHER PROTOCOL NUMBERS    VEU 104. IND BB4705
STUDY DESIGN              Double-Blind; Randomized; Placebo-Controlled;
                          2-Arm
PROTOCOL DETAILS          STUDY INTENT: Vaccine prophylaxis,
                          Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients. (16 patients
                          receive vaccine, 8 patients receive placebo)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 months, with
                          follow-up once or twice yearly for at least 5
                          years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 34/24 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 10 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 infection. 2. CD4 count >= 400
                          cells/mm3. 3. No AIDS-defining illness or
                          other systemic manifestations related to HIV
                          (other than generalized lymphadenopathy). 4.
                          HIV p24 < 30 pg/ml. 5. Proven pregnancy in
                          the 16th to 24th week of gestation at study
                          entry, with no special obstetrical risks. 6.
                          Concurrent AZT therapy is permitted. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: > 28 percent.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3. ( 400
                          - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Total white blood count >= 3000
                          cells/mm3.
PATIENT AGE               AGE: 16 Years - 40 Years.
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Pregnant. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. AZT. 2.
                          Acyclovir.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 15 Years. 41 Years - 99 Years.
PATIENT EXCLUSION CRIT.   SEX: MALE
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current use of illicit drugs
                          or known chronic alcohol use.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Antiretroviral or
                          immunomodulating agent other than AZT within
                          90 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded:
                          Antiretroviral or immunomodulating agent
                          other than AZT during the pregnancy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Known hypersensitivity to a component of the
                          vaccine. 2. Evidence of fetal abnormality on
                          ultrasound. 3. Evidence of maternal risk
                          factors including insulin-dependent diabetes,
                          moderate to severe hypertension, repeated
                          fetal wastage (> 3), Rh-sensitization or
                          other blood group alloimmunization, severe
                          renal disease, previous infants with
                          malformations or other factors that
                          obstetrically are judged to constitute a
                          special risk of spontaneous abortion or
                          premature birth. 4. Active syphilis. 5.
                          Hepatitis B surface antigen positive.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0153  rgp120/HIV-1MN
MANUFACTURERS             Drug 1: Genentech Incorporated 460 Point San
                          Bruno Boulevard South San Francisco, CA 94080
                          Contact: Professional Services (800)
                          821-8590.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 300 mcg (or placebo)
                          administered between week 16 and week 24 of
                          gestation, followed by monthly booster
                          injections concluding at end of pregnancy for
                          a total of 5 injections, witoptional booster
                          immunizations at 3, 6, 9, and 12 months after
                          delivery
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intramuscular
                          injection, 300 mcg vials
OTHER TREATMENT INFO.     END POINT: Outcome of pregnancy, clinical and
                          virological course of maternal HIV disease,
                          maternal immune responses, and incidence of
                          definitive HIV infection in the infants.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Progression of
                          HIV disease, defined by occurrence of an
                          AIDS-defining illness, increase in p24 to
                          over 80 pg/ml, or decrease in CD4 count to <
                          200 cells/mm3 or <= 50 percent of baseline on
                          two consecutive determinations. 2.
                          Intolerance to the vaccine. 3. Evidence of
                          fetal abnormality. 4. Pregnancy complications
                          necessitating or resulting in preterm
                          delivery.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), National Institute of
                          Allergy & Infectious Diseases (VEU).
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              HIV Envelope Protein gp120/*ADVERSE EFFECTS/
                          IMMUNOLOGY
MESH HEADING              HIV Infections/IMMUNOLOGY/*THERAPY
MESH HEADING              Human
MESH HEADING              Pregnancy
MESH HEADING              Pregnancy Complications, Infectious
MESH HEADING              Vaccines, Synthetic
CAS REGISTRY NUMBER       0 (HIV Envelope Protein gp120)
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
LAST REVISION DATE        941207
ENTRY MONTH               9304
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840ACTU: 0801.
MARYLAND                  Johns Hopkins University / Center for
                          Immunization Research Hampton House Rm 125 /
                          624 North Broadway Baltimore, MD 21205
                          Contact: Karen Charron (410) 955-7283 OPEN
                          930910 ACTU: 6002.
MARYLAND                  The Johns Hopkins University ( Pediatrics )
                          600 North Wolfe Street Baltimore, MD 21287
                          Contact: Laura J Belcher (410) 955-9749 OPEN
                          940228 ACTU: 3701.
MISSOURI                  St Louis University School of Medicine / Sec
                          Inf Dis 1402 South Grand Boulevard St Louis,
                          MO 63104 Contact: Dr Robert B Belshe (314)
                          577-8648 Contact: Heidi Israel (314) 577-8649
                          OPEN 930409 ACTU: 6007.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940422 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 940422
                          ACTU: 2102.
NEW YORK                  University of Rochester Medical Center Box
                          689 / Room 36209 / 601 Elmwood Avenue
                          Rochester, NY 14642 Contact: Dr Michael
                          Keefer (716) 275-0810 OPEN 930430 ACTU: 6005.
 
35
UNIQUE IDENTIFIER         NIH/00518
PROTOCOL ID NUMBERS       NIAID ACTG 232
PROTOCOL TITLE            A Phase I Clinical Trial to Study the
                          Toxicity, Pharmacokinetics, and Efficacy of a
                          Human Monoclonal Antibody, F105, for Treating
                          Human Immunodeficiency Virus Infection.
VERSION NUMBER & DATE     2 (940930)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Samore MH
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          pharmacokinetics of F105 human monoclonal
                          antibody both following a single dose and
                          during intermittent administration in
                          HIV-infected patients. To determine specific
                          dose concentrations sufficient to achieve
                          efficacy and avoid toxicity. To determine the
                          effect of F105 on virologic and serologic
                          parameters.
GENERAL DESCRIPTION       RATIONALE: Early in the course of HIV
                          infection, the primary humoral immune
                          response appears to be highly strain specific
                          and to be directed at a hypervariable portion
                          of the viral gp120. The F105 human monoclonal
                          antibody reacts with the CD4 binding region
                          of gp120 and has been shown to neutralize the
                          IIIB, SF2, and MN strains of HIV at
                          concentrations readily achievable in humans.
GENERAL DESCRIPTION       METHODOLOGY: In Part A, cohorts of four
                          patients each receive a single intravenous
                          (IV) injection of F105 human monoclonal
                          antibody at 100, 500, or 1000 mg/m2. The IV
                          catheter will remain in the patient's arm for
                          12 hours after injection for subsequent
                          drawing of blood samples. The third group
                          (1000 mg/m2) will be studied only after the
                          first two groups are analyzed for
                          pharmacokinetics. No more than two patients
                          are enrolled per week. Patients on Part A
                          undergo follow-up three to four times within
                          the first week after injection and weekly
                          thereafter for 7 weeks. Pharmacokinetic and
                          toxicity data generated from Part A will be
                          used to select two dose levels for
                          intermittent administration in Part B. In
                          this part, cohorts of four to six patients
                          receive one of two doses of F105 for 8-12
                          weeks. Per 9/30/94 amendment, eight patients
                          receive one dose of F105 (500 mg/m2) every 21
                          days for four doses (dose determined from
                          analysis of Part A data).
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 infection as documented
                          by ELISA confirmed by Western blot. 2. CD4
                          count (within 15-90 days prior to study
                          entry) of 200 - 500 cells/mm3 for Part A or
                          100 - 400 cells/mm3 for Part B (per 9/30/94
                          amendment). 3. No diagnosis of AIDS (Part A
                          only, per 9/30/94 amendment). Part B patients
                          only (per 9/30/94 amendment): 1. Primary
                          (viral) isolates sensitive to F105 antibody
                          using the yield reduction assay currently
                          under development by ACTG, determined within
                          15-90 days prior to study entry. 2. Plasma
                          viremia by qualitative plasma culture. 3. NO
                          active opportunistic infection within 6 weeks
                          prior to drawing of first isolate. 4. NO
                          AIDS-related malignancy other than minimal
                          Kaposi's sarcoma.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    IND BB5090
STUDY DESIGN              Open Label; Dose Escalating; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy, Pharmacokinetics,
                          Immunotherapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients. (12 patients
                          in Part A; 8 patients in Part B)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Part A: At
                          least 8 weeks. Part B: At least 8-12 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 8/20 (941012).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV-1 infection. 2. CD4
                          count 200 - 500 cells/mm3 (Part A) or 100 -
                          400 cells/mm3 (Part B, per amendment). 3. No
                          diagnosis of AIDS (Part A only, per
                          amendment). 4. Life expectancy of at least 6
                          months. Part B patients only (per amendment):
                          Primary (viral) isolates sensitive to F105
                          antibody using the yield reduction assay
                          currently under development by ACTG,
                          determined within 15-90 days prior to study
                          entry. 2. Plasma viremia by qualitative
                          plasma culture. 3. NO active opportunistic
                          infection within 6 weeks prior to drawing of
                          first isolate. 4. NO AIDS-related malignancy
                          other than minimal Kaposi's sarcoma. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.5 g/dl. (Must not be
                          transfusion dependent).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3.
                          (Part A only). ( 200 - 300 - 400 - 500 ). 100
                          - 400 cells/mm3 (Part B only, per amendment).
                          ( 100 - 200 - 300 - 400 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.8 mg/dl. (Part A only).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 70 ml/min. (If
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. Prothrombin <= 1.5 x ULN (Part A
                          only). Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior AZT or other
                          nucleoside antiviral agents.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: PART B ONLY. Allowed:
                          Concomitant AZT or other antiretroviral drugs
                          if patient is on a stable dose of such
                          therapy within 3 months prior to study entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active alcohol or drug abuse
                          that may compromise ability to comply with
                          study requirements.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Red cell
                          transfusions administered to maintain
                          hemoglobin at acceptable level or alleviate
                          symptoms of anemia.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 6 weeks
                          prior to study entry: 1. Intravenous gamma
                          globulin. 2. Chemotherapy. 3.
                          Corticosteroids. 4. Other experimental
                          therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: EXCLUDED IN ALL
                          PATIENTS: 1. Immunosuppressive treatments,
                          cytokine therapy, or biologic response
                          modifiers not included in this study,
                          including interferons or adjuvant treatment
                          for chronic and severe fungal infections such
                          as cryptococcal meningitis. 2. Intravenous
                          gamma globulin. 3. Chemotherapy. 4.
                          Corticosteroids. 5. Other experimental
                          therapy. 6. G-CSF, GM-CSF, or erythropoietin.
                          EXCLUDED IN PART A ONLY: Drugs known to
                          enhance or block metabolism of other drugs.
                          EXCLUDED IN PART B ONLY: AZT or other
                          antiretroviral drugs IF INITIATED during or
                          within 1 month after completion of study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Evidence
                          of active renal disease as manifested by
                          sediment containing red or white cell casts.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0192  F105 human monoclonal
                          antibody
MANUFACTURERS             Drug 1: Centocor Incorporated 200 Great
                          Valley Parkway Malvern, PA 19355-1307
                          Contact: Dr Richard McCloskey (610) 889-4793
                          Contact: pager (215) 452-8233.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Part A: 100, 500, or
                          1000 mg/m2 in a single dose over 6min, via
                          infusion pump. Part B: Doses to be determined
                          following analysis of pharmacokidata in Part
                          A, administered for 8-12 weeks. Per 9/30/94
                          amendm500 mg/m2 q 21 days for four doses
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, 5.0 mg/ml
                          vials
OTHER TREATMENT INFO.     END POINT: Part A: Safety and pharmacokinetic
                          parameters. Part B: Safety, virologic
                          parameters to assess preliminary efficacy,
                          pharmacokinetics, changes in CD4 counts.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: PART A: Grade 3 or
                          worse cytopenia. PART B: 1. Dose-limiting
                          toxicity. 2. Condition has deteriorated and
                          requires new antiretroviral therapy. 3. New
                          medical illness intervenes. 4. An event
                          occurs that would seriously limit patient
                          compliance or preclude continuation on study.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antibodies, Monoclonal/*ADVERSE EFFECTS/
                          IMMUNOLOGY
MESH HEADING              Female
MESH HEADING              HIV Infections/*THERAPY
MESH HEADING              Human
MESH HEADING              Immunization, Passive
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antibodies, Monoclonal)
LAST REVISION DATE        941207
ENTRY MONTH               9401
MASSACHUSETTS             New England Deaconess Hospital 185 Pilgrim
                          Road Boston, MA 02215 Contact: Helen Fitch
                          (617) 735-0785 OPEN 941207 ACTU: 0103.
 
36
UNIQUE IDENTIFIER         NIH/00509
PROTOCOL ID NUMBERS       NIAID ACTG 230
PROTOCOL TITLE            A Phase I Study to Evaluate the Safety and
                          Immunogenicity of Recombinant HIV-1 Envelope
                          Antigen in Children Born to HIV-Infected
                          Mothers.
VERSION NUMBER & DATE     3 (940719)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            HIV Negative
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Vaccines
PROTOCOL CHAIRS           CHAIR  Borkowsky W
PROTOCOL CHAIRS           CO-CHAIR  Wara D
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To determine the safety of
                          envelope recombinant proteins rgp120/HIV-1MN
                          and rgp120/HIV-1SF2 in infants who are of
                          indeterminate HIV status born to HIV-infected
                          women. To evaluate changes in viral load in
                          infants proven to be infected and absolute
                          CD4 counts in all immunized infants.
                          SECONDARY: To evaluate the immunogenicity of
                          these envelope recombinant proteins in
                          infants of indeterminate HIV status born to
                          HIV-infected women.
GENERAL DESCRIPTION       RATIONALE: Only 30-50 percent of HIV-infected
                          infants have detectable virus at birth.
                          Successful early sensitization to HIV
                          envelope epitopes may help prevent infection
                          or, alternatively, may enhance HIV-specific
                          immune function to alter HIV replication and
                          disease progression.
GENERAL DESCRIPTION       METHODOLOGY: Newborns are randomized to one
                          of three different doses of either
                          rgp120/HIV-1MN or rgp120/HIV-1SF2 or their
                          matching placebos. At each dose level, 12
                          patients receive vaccine and three patients
                          receive placebo. Immunizations are performed
                          at 0, 4, 12, and 20 weeks, and patients are
                          followed until 2 years of age. Three of four
                          patients treated at a given dose level must
                          have received two immunizations without
                          evidence of grade 3 or 4 clinical or
                          laboratory toxicity before dose escalation
                          occurs. Twelve additional patients are
                          treated with the optimal dose of each vaccine
                          at weeks 0, 4, 8, and 20, accompanied by
                          three additional placebo patients per
                          vaccine.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940928)
DISEASE STUDIED           Primary HIV infection, Healthy.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. > 37 weeks gestation and < 72
                          hours of age born to HIV-infected women. 2.
                          NOT born to women who received either passive
                          or active immunotherapy during pregnancy. 3.
                          NOT breast-fed. 4. NOT born to women who are
                          hepatitis B surface antigen positive. 5.
                          Receiving AZT at study entry (except infants
                          enrolled in ACTG 076).
ELIGIBILITY               ASYM. HIV Seronegative.
OTHER PROTOCOL NUMBERS    IND BB 4714
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Dose Comparison; Drug Comparison
PROTOCOL DETAILS          STUDY INTENT: Immunology, Drug safety,
                          Vaccine prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 120 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 104 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 106/120 (940928).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 37 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must be:
                          1. > 37 weeks gestation and < 72 hours of age
                          born to HIV-infected women. 2. NOT born to
                          women who received either passive or active
                          immunotherapy during pregnancy. 3. NOT
                          breast-fed. 4. NOT born to women who are
                          hepatitis B surface antigen positive. 5.
                          Receiving AZT at study entry (except infants
                          enrolled in ACTG 076). NOTE: Parent or
                          guardian must provide informed consent and be
                          willing to comply with study requirements.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 12.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN. (ULN = upper limit of
                          normal for age).
PATIENT INCLUSION CRIT.   CREATININE: < 1.3 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 1500 cells/mm3.
PATIENT AGE               AGE: 01 Days - 03 Days.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral therapy. 2. Coenrollment in a
                          therapeutic protocol if begun at least 30
                          days following the week 20 immunization. 3.
                          Routine immunizations if given more than 1
                          week before or after study vaccine.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Passive
                          or active HIV-specific immunotherapy other
                          than the study candidate vaccines. 2.
                          Investigational medications.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded:
                          Documented or suspected serious bacterial
                          infection, metabolic illness, or other
                          immediate life-threatening conditions.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0153  rgp120/HIV-1MN
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0103  rgp120/HIV-1SF2
MANUFACTURERS             Drug 1: Genentech Incorporated 460 Point San
                          Bruno Blvd South San Francisco, CA 94080
                          Contact: Dr Don Francis (415) 255-5806.
MANUFACTURERS             Drug 2: The BIOCINE Company 4560 Horton
                          Street Emeryville, CA 94608-2916 Contact: Dr
                          Anne-Marie Duliege (510) 601-2715.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 30, 100, or 300 mcg
                          (or placebo) at weeks 0, 4, 12, and20. Drug
                          2: 5, 15, or 50 mcg (or placebo) at weeks 0,
                          4, 12 and 20
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intramuscular. Drug 2:
                          Intramuscular, 300 mcg vials
OTHER TREATMENT INFO.     END POINT: Vaccine safety, effects on viral
                          load and absolute CD4 counts, immunogenicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          (grade 4 or recurrent grade 3) toxicity. 2.
                          Disease progression to P-2 status
                          specifically for the following: -
                          AIDS-defining opportunistic infection. -
                          Wasting disease or failure to thrive. -
                          HIV-associated progressive encephalopathy. -
                          HIV-associated malignancy. - Two or more
                          episodes of bacterial septicemia and/or
                          meningitis. - Hypogammaglobulinemia (IgG) <
                          250 mg/dl. 3. Immunological decline defined
                          as <= 20 percent CD4, regardless of HIV
                          infection status. 4. Noncompliance. 5. At the
                          request of the patient, parent or guardian,
                          investigator, FDA, IND sponsor, or
                          pharmaceutical companies.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 toxicity: If
                          toxicity resolves to grade 2 or better prior
                          to the next scheduled immunization,
                          administer vaccine at 50 percent dose; if
                          toxicity has not resolved or if it recurs,
                          discontinue immunizations permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), The BIOCINE Company,
                          Genentech Incorporated.
MESH HEADING              Female
MESH HEADING              HIV/*IMMUNOLOGY
MESH HEADING              HIV Envelope Protein gp120/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS/IMMUNOLOGY
MESH HEADING              HIV Infections/*PREVENTION & CONTROL/THERAPY
MESH HEADING              Human
MESH HEADING              Infant, Newborn
MESH HEADING              Male
MESH HEADING              Vaccines, Synthetic
MESH HEADING              Virus Replication/DRUG EFFECTS
CAS REGISTRY NUMBER       0 (HIV Envelope Protein gp120)
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
LAST REVISION DATE        940928
ENTRY MONTH               9308
CALIFORNIA                Harbor General / UCLA Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 940701 ACTU: 3609.
CALIFORNIA                UCLA Medical Center / Pediatrics 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          940706 ACTU: 3601.
CALIFORNIA                Long Beach Memorial Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 940706 ACTU: 3606.
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 940706
                          ACTU: 4601.
CALIFORNIA                UCSF / Moffitt Hospital 602 / Pediatrics 505
                          Parnassus / Box 0105 San Francisco, CA
                          94143-0105 Contact: Debbie Trevithick (415)
                          476-6480 OPEN 940706 ACTU: 4501.
CALIFORNIA                San Francisco General Hospital (Pediatric)
                          Box 0105 Moffitt Hospital 602 / 505 Parnassus
                          San Francisco, CA 94143-0105 Contact: Debbie
                          Trevithick (415) 476-6480 OPEN 940706 ACTU:
                          4502.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 940706 ACTU:
                          7001.
CONNECTICUT               Yale University School of Medicine PO Box
                          3333 / 333 Cedar Street New Haven, CT
                          06510-8064 Contact: Unspecified (203)
                          737-4040 OPEN 941005 ACTU: 5038.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 940706 ACTU: 4001.
ILLINOIS                  Cook County Hospital / Childrens Memorial
                          2300 Childrens Plaza Box #20 Chicago, IL
                          60614-3394 Contact: Debbie Fonken (312)
                          880-4757 OPEN 940706 ACTU: 4002.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 940706 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 940706 ACTU: 7201.
LOUISIANA                 Univ Hospital / Tulane Univ Med Schl / Tulane
                          - LSU Ped ACTU 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 941003 ACTU: 7204.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street / SHU-Main 3
                          Springfield, MA 01199 Contact: MaryPat Toye
                          (413) 784-5399 OPEN 940706 ACTU: 7302.
MASSACHUSETTS             University of Massachusetts Medical School /
                          Dept of Peds 55 Lake Avenue North Worcester,
                          MA 01655-0001 Contact: Joanne Shepard (508)
                          856-1692 OPEN 940706 ACTU: 7301.
MASSACHUSETTS             Children's Hospital 300 Longwood Avenue /
                          Carnegie 3 Boston, MA 02115 Contact: Robert
                          Bishop (617) 735-8198 OPEN 940706 ACTU: 2901.
MASSACHUSETTS             Boston City Hospital / Ped Infect Dis /
                          Finland Lab 774 Albany Street / Finland Lab
                          Room 301 Boston, MA 02118 Contact: Anne Marie
                          Reagan (617) 534-5813 OPEN 940706 ACTU: 2903.
MARYLAND                  The Johns Hopkins University ( Pediatrics )
                          600 North Wolfe Street Baltimore, MD 21287
                          Contact: Laura J Belcher (410) 955-9749 OPEN
                          940706 ACTU: 3701.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 940706 ACTU:
                          4701.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 940706 ACTU: 2801.
NEW JERSEY                Univ of Med & Dentistry of NJ / Univ Hospital
                          15 South Ninth Street Newark, NJ 07107-2198
                          Contact: George Donavan Mcsherry (201)
                          268-8273 OPEN 940706 ACTU: 2802.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          Ninth Street Newark, NJ 07107-2198 Contact:
                          George Donavan McSherry (201) 268-8273 OPEN
                          940706 ACTU: 2803.
NEW YORK                  Beth Israel Medical Center / Pediatrics First
                          Avenue at 16th Street Dazian Pavilion Tenth
                          Floor New York, NY 10003 Contact: Ann Marshak
                          (212) 420-4432 OPEN 940706 ACTU: 4302.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue / Pediatric
                          New York, NY 10016 Contact: Nagamah Deygoo
                          (212) 263-6426 OPEN 940706 ACTU: 4401.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940706 ACTU:
                          4301.
NEW YORK                  Incarnation Children's Ctr / c/o Columbia
                          Presb Med Ctr 142 Audubon Avenue New York, NY
                          10032 Contact: Pam Clark (212) 928-2228 OPEN
                          940706 ACTU: 4103.
NEW YORK                  The Columbia Presbyterian Medical Hosp
                          (Pediatric) 622 West 168th St Room 1161 New
                          York, NY 10032-3796 Contact: Kathy A Shea
                          (212) 305-7222 OPEN 940706 ACTU: 4101.
NEW YORK                  Bronx Lebanon Hospital Center / Department of
                          Pediatrics 1650 Selwyn Avenue Room 2C Bronx,
                          NY 10457 Contact: Patrice Edwards-Cihak (718)
                          960-1015 OPEN 940706 ACTU: 6901.
NEW YORK                  SUNY Health Science Center at Stony Brook HSC
                          T 15 080 Stony Brook, NY 11794-8111 Contact:
                          Peggy Melendez (516) 444-1313 Contact: (516)
                          444-7692 Contact: beeper (516) 282-8808
                          Contact: Jeannie Conner (516) 444-2724 OPEN
                          940706 ACTU: 5040.
NEW YORK                  SUNY Health Science Center at Syracuse 750
                          East Adams Street Syracuse, NY 13210 Contact:
                          Kathie Shea-Contello (315) 464-6331 OPEN
                          940706 ACTU: 5039.
NEW YORK                  Children's Hospital 219 Bryant Street
                          Buffalo, NY 14222 Contact: Cynthia Kelly
                          (716) 878-7908 OPEN 940706 ACTU: 1104.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940706 ACTU: 1101.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 940706 ACTU: 5031.
PENNSYLVANIA              Hospital of the Univ of PA / Children's Hosp
                          of Philadelphia 3400 Spruce Street Maloney
                          Building 2Nd Floor Philadelphia, PA 19104
                          Contact: Kathy Mooney (215) 662-3225 OPEN
                          940706 ACTU: 6702.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 940706 ACTU: 6701.
 
37
UNIQUE IDENTIFIER         NIH/00488
PROTOCOL ID NUMBERS       NIAID ACTG 228
PROTOCOL TITLE            CMV Retinitis Retreatment Trial.
VERSION NUMBER & DATE     3 (921201)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To assess the safety and efficacy of
                          three therapeutic regimens (foscarnet,
                          ganciclovir, or the combination) for
                          recurrent or persistent AIDS-related
                          cytomegalovirus (CMV) retinitis.
GENERAL DESCRIPTION       RATIONALE: Although therapy with foscarnet or
                          ganciclovir halts retinitis progression in 90
                          percent of patients treated, relapses are
                          common and may accelerate due to development
                          of drug resistance, deteriorating immune
                          function, or other factors. Treatment
                          strategies currently being investigated
                          include switching patients from one drug to
                          the other or combining the two drugs.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive foscarnet, ganciclovir, or a
                          combination of the two drugs (administered
                          sequentially). Initially, patients undergo
                          single or multiple cycles of induction
                          therapy for 14 days followed by maintenance
                          therapy. Patients in whom the retinitis
                          continues to progress or who are intolerant
                          of the initial treatment switch to the
                          alternative drug for further cycles of
                          induction and maintenance. Patients on the
                          combination arm in whom retinitis continues
                          to progress are given further cycles of the
                          combination at an increased dose, or, if one
                          drug is causing toxicity, are given further
                          cycles with the alternative drug. Patients
                          are followed monthly for 6 months and then
                          every 3 months thereafter.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection or
                          AIDS by CDC criteria. 2. Active CMV retinitis
                          after 28 or more days of either foscarnet or
                          ganciclovir therapy. 3. At least one lesion
                          with one-quarter disk area or more that can
                          be photographed. 4. Visual acuity of 3 or
                          more letters on ETDRS (Early Treatment
                          Diabetic Retinopathy Study) chart at 1 meter
                          (5/200 Snellen) in an affected eye.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Multicenter; Randomized; 3-Arm; Comparative
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 300 patients. (100 per
                          treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until death or
                          study termination.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 184/300 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection or AIDS. 2. Active CMV
                          retinitis after 28 or more days of either
                          foscarnet or ganciclovir therapy. 3. At least
                          one lesion with one-quarter disk area or more
                          that can be photographed. 4. Visual acuity of
                          3 or more letters on ETDRS chart (5/200
                          Snellen) in an affected eye. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 20000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 500 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: At least 28 days
                          of prior foscarnet or ganciclovir.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: G-CSF.
                          Recommended: Antiretroviral therapy.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of intolerance to ganciclovir or
                          foscarnet sufficient to contraindicate use.
                          2. History of combination
                          foscarnet/ganciclovir therapy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug or alcohol abuse
                          sufficient to prevent compliance.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Media opacity severe enough to preclude
                          visualization of both fundi. 2. Retinal
                          detachment not scheduled for surgical repair.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0017  Foscarnet sodium
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0018  Ganciclovir
TRADE NAME OF SUBSTANCE   Drug 1 Foscavir
TRADE NAME OF SUBSTANCE   Drug 2 Cytovene
MANUFACTURERS             Drug 1: Johns Hopkins University / SOCA 615
                          North Wolfe Street Room 5010 Baltimore, MD
                          21205 Contact: Janet Holbrook (410) 955-8175
                          Contact: (410) 955-0930.
MANUFACTURERS             Drug 2: Syntex Laboratories Incorporated 3401
                          Hillview Avenue / PO Box 10850 Palo Alto, CA
                          94303 Contact: Unspecified (800) 444-4200.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Arms 1 and 2: 90
                          mg/kg/12 hr for 14 days as induction,
                          followed by 120 mg/kg/day as maintenance.
                          Foscarnet is given asfirst drug in Arm 1 and
                          as the second drug (after progression) Arm 2.
                          Arm 3: 90 mg/kg/day for 14 days OR 90
                          mg/kg/12 hr for 14 days ainduction, followed
                          by 90 mg/kg/day as maintenance for the
                          inittreatment or 120 mg/kg/day as maintenance
                          for the post-progresstreatment. Drug 2: Arms
                          1 and 2: 5 mg/kg/12 hr for 14 days as
                          induction, followed by 10 mg/kg/day as
                          maintenance. Ganciclovir is given asecond
                          drug (after progression) in Arm 1 and as the
                          first drug Arm 2. In Arm 2, patients
                          requiring additional induction
                          receivincreased dose of 7.5 mg/kg/day. Arm 3:
                          5 mg/kg/12 hr for 14 days OR 5 mg/kg/day for
                          14 days as induction, followed by 5 mg/kg/day
                          as maintenance for both the initial treatment
                          and the post-progression treatment
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Induction: 90 - 180
                          mg/kg. Maintenance: 90 - 120 mg/kg.Drug 2:
                          Induction: 5 - 10 mg/kg. Maintenance: 5 - 10
                          mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous. Drug 2:
                          Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: Until patient death or
                          study termination.
OTHER TREATMENT INFO.     END POINT: Mortality, CMV retinitis
                          progression, loss of visual function,
                          toxicity, retinal detachment, morbidity,
                          quality of life.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Unacceptable
                          toxicity.
OTHER TREATMENT INFO.     MODIFICATION: For serum creatinine >= 3.0
                          mg/dl: hold foscarnet therapy, then restart
                          if toxicity resolves to <= 2.0 mg/dl. For ANC
                          < 500 cells/mm3 and platelets < 10000
                          cells/mm3: hold ganciclovir until ANC >= 750
                          cells/mm3 and platelets >= 20000 cells/mm3.
                          For other drug-related grade 4 toxicity:
                          discontinue treatment.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Foscarnet/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Ganciclovir/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       4428-95-9 (Foscarnet)
CAS REGISTRY NUMBER       82410-32-0 (Ganciclovir)
LAST REVISION DATE        941207
ENTRY MONTH               9301
CALIFORNIA                University of California San Diego 9500
                          Gilman Drive / Clinical Sciences Bldg
                          LaJolla, CA 92093-0672 Contact: Candace
                          McIvor (619) 534-7170 OPEN 930113 ACTU: 0701.
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 930113 ACTU: 0808.
LOUISIANA                 Tulane University / Charity Hospital 1430
                          Tulane Avenue New Orleans, LA 70112-2699
                          Contact: Russell Strada (504) 584-1692
                          Contact: (504) 584-3605 OPEN 930413 ACTU:
                          1702.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 930113 ACTU: 0401.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          930427 ACTU: 1801.
 
38
UNIQUE IDENTIFIER         NIH/00504
PROTOCOL ID NUMBERS       NIAID ACTG 227
PROTOCOL TITLE            Phase I Safety and Pharmacokinetics Study of
                          Microparticulate Atovaquone (m-Atovaquone;
                          566C80) in HIV-Infected Infants and Children.
VERSION NUMBER & DATE     2 (940930)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Hughes W
PROTOCOL CHAIRS           CO-CHAIR  Dorenbaum A
GENERAL DESCRIPTION       PURPOSE: To determine the safety, tolerance,
                          and pharmacokinetics of a new improved
                          microparticulate suspension formulation of
                          atovaquone administered at one of two dose
                          levels (per 09/30/94 amendment, a third dose
                          level was added) daily for 12 days in
                          HIV-infected infants and children who are at
                          risk of developing Pneumocystis carinii
                          pneumonia (PCP).
GENERAL DESCRIPTION       RATIONALE: Atovaquone has shown prophylactic
                          potential in adults in the treatment of PCP
                          but is poorly absorbed in tablet form. To
                          improve the bioavailability of atovaquone, a
                          new formulation has been prepared as a
                          microparticulate suspension. Since studies in
                          adults have demonstrated substantial safety
                          of this drug, evaluation in children is being
                          pursued.
GENERAL DESCRIPTION       METHODOLOGY: Three cohorts of four patients
                          each (ages 2-12 years, 3 months to < 2 years,
                          and 1 month to < 3 months) receive 10 mg/kg
                          atovaquone daily for 12 days. The oldest age
                          group is treated first. In the absence of
                          unacceptable toxicity, the dose of atovaquone
                          is escalated to 30 mg/kg daily in subsequent
                          4-patient cohorts representing each of the
                          age stratifications and (per 9/30/94
                          amendment) to 45 mg/kg in a separate
                          4-patient cohort aged 3 months to < 2 years.
                          If two of four patients in a given cohort
                          experience unacceptable toxicity at the
                          initial dose, two additional patients in the
                          same age range are entered. Blood samples are
                          drawn for pharmacokinetic evaluation.
                          Patients are followed to day 24. Per 9/30/94
                          amendment, patients aged 3 months to < 2
                          years of age who received 10 or 30 mg/kg may
                          re-enroll in the 45 mg/kg cohort after a
                          1-month washout.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Symptoms of AIDS by CDC
                          definition OR documented HIV infection as
                          follows: o Infants < 15 months of age -
                          Positive viral culture of PBMC AND either a
                          second separate confirmatory test (positive
                          viral culture, p24 antigen, or PCR) or
                          evidence of Class P-2 (Subclass A, C, or F)
                          symptomatic HIV infection. o Children >= 15
                          months of age - Criteria as listed for
                          infants < 15 months OR two or more positive
                          tests for HIV antibody by ELISA, with at
                          least one test confirmed by Western blot or
                          IFA. NOTE: Umbilical cord blood is not
                          acceptable for confirmatory tests. 2. At risk
                          of developing PCP and requiring prophylaxis
                          according to MMWR guidelines.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 41,828
STUDY DESIGN              Dose Escalating; Open Label; Pharmacokinetic;
                          Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Pharmacokinetics,
                          Bioavailability, Drug prophylaxis, Drug
                          toxicity.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 24 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 days.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 18/24 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS or documented HIV infection. 2.
                          Risk of developing PCP. 3. Normal EKG and
                          chest radiograph. 4. No blood or protein on
                          urinalysis. 5. Consent of parent or guardian.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl. (< two years of
                          age); >= 10.0 g/dl (>= two years of age).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1200 cells/mm3. BUN <
                          35 mg/dl. Uric acid <= 10 mg/dl.
                          Amylase/lipase < 1.5 x ULN. PT <= 20 seconds.
                          PTT <= 35 seconds (except in patients with
                          hereditary clotting factor deficiencies).
PATIENT AGE               AGE: 01 Months - 12 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test.
OTHER PATIENT INCL. CH.   WEIGHT: >= 4 kg.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Prophylactic
                          TMP/SMX if given no less than 3 days prior to
                          study entry. 2. Prophylactic aerosolized
                          pentamidine (or a single intravenous dose of
                          4.0 mg/kg pentamidine) if given no less than
                          7 days prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Zidovudine
                          (AZT). 2. Dideoxycytidine (zalcitabine; ddC).
                          3. Didanosine (ddI). 4. Nonaminoglycoside,
                          nonmacrolide, and nonsulfonamide antibiotics.
                          7. Factor VIII. 8. IVIG.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of G6PD deficiency. 2. Prior
                          enrollment on this study. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 29 Days. 13 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test.
PATIENT EXCLUSION CRIT.   WEIGHT: < 4 kg.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Trimethoprim/sulfamethoxazole. 2. Sulfadoxine
                          and pyrimethamine (Fansidar). 3. Primaquine.
                          4. Aspirin. 5. Amphotericin B. 6.
                          Aminoglycoside antibiotics. 7. Sulfonamides.
                          8. Dapsone. 9. Benzodiazepines. 10. Rifampin.
                          11. Erythromycin, clarithromycin, and
                          azithromycin. 12. Digitalis. 13.
                          Para-aminosalicylic acid (PAS). 14.
                          Isoniazid. 15. Anticoagulants. 16. Any other
                          investigational therapies.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Anticipated organ system or laboratory
                          abnormalities (other than immune system
                          abnormalities) from the primary disease and
                          its treatment during the study. 2. Acute or
                          chronic infections requiring treatment during
                          the study. NOTE: Thrush and herpes labialis
                          are allowed if these conditions do not
                          require treatment. 3. Diarrhea or vomiting.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0084  Atovaquone
TRADE NAME OF SUBSTANCE   Drug 1 566C80
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 10, 30, or 45 mg/kg
                          daily for 12 days
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 10, 30, or 45 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, syrup
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 days.
OTHER TREATMENT INFO.     END POINT: Toxicity, pharmacokinetics.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. More than three doses of drug
                          missed.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Antifungal Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Biological Availability
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Naphthoquinones/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *PREVENTION & CONTROL
CAS REGISTRY NUMBER       0 (Antifungal Agents)
CAS REGISTRY NUMBER       94015-53-9 (atovaquone)
LAST REVISION DATE        941207
ENTRY MONTH               9306
CALIFORNIA                UCSF / Moffitt Hospital 602 / Pediatrics 505
                          Parnassus / Box 0105 San Francisco, CA
                          94143-0105 Contact: Debbie Trevithick (415)
                          476-6480 OPEN 930630 ACTU: 4501.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 930615 ACTU: 4001.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          940506 ACTU: 6601.
 
39
UNIQUE IDENTIFIER         NIH/00648
PROTOCOL ID NUMBERS       NIAID ACTG 226
PROTOCOL TITLE            A Pharmacokinetic and Tolerance Study of Oral
                          Ganciclovir in HIV-Infected Children With
                          Asymptomatic Cytomegalovirus Infection and
                          Low CD4 Cell Counts or Quiescent
                          Cytomegalovirus Disease.
VERSION NUMBER & DATE     1 (940726)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
PROTOCOL CHAIRS           CHAIR  Frenkel L
PROTOCOL CHAIRS           CO-CHAIR  Dankner W
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To determine the
                          pharmacokinetics, MTD, and long-term safety
                          and tolerance of oral ganciclovir in
                          HIV-infected infants, children, and
                          adolescents. SECONDARY: To evaluate the
                          effect of oral ganciclovir on the virologic
                          parameters of CMV.
GENERAL DESCRIPTION       RATIONALE: Maintenance treatment with
                          intravenous (IV) ganciclovir for
                          cytomegalovirus retinitis in AIDS patients is
                          now standard therapy, but daily IV therapy
                          can be complicated by catheter infections and
                          thrombosis. An oral regimen of ganciclovir
                          has been administered safely in adult AID
                          patients and may be of significant benefit to
                          children as well.
GENERAL DESCRIPTION       METHODOLOGY: Patients are assigned to one of
                          four oral (syrup or capsules) dose levels
                          following a single intravenous dose of
                          ganciclovir. Treatment continues for 24 weeks
                          total.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (941207)
DISEASE STUDIED           Cytomegalovirus infection ( CMV infection ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection as evidenced by
                          positive viral culture, with a second
                          confirmatory test of positive viral culture,
                          p24 antigen, or PCR. If >= 18 months of age,
                          HIV infection may also be demonstrated by
                          ELISA confirmed by Western blot or IFA
                          (provided both tests are obtained after 18
                          months of age). NOTE: Cord blood is not
                          acceptable for diagnosis. 2. CMV infection
                          documented by body fluid or tissue culture.
                          (If >= 12 months of age, CMV infection may be
                          documented by serology). 3. CD4 count < 150
                          cells/mm3 or < 15 percent AND/OR quiescent
                          CMV disease. Quiescent CMV disease is defined
                          as non-sight-threatening CMV retinitis that
                          is clinically stable for at least 4 weeks,
                          CMV gastrointestinal disease that is
                          clinically stable for at least 2 weeks,
                          congenital CMV infection with hepatitis
                          and/or thrombocytopenia, or other CMV
                          quiescent disease that has been discussed
                          with the protocol chair. 4. NO loss of sight
                          from CMV retinitis. 5. NO acute opportunistic
                          infection.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 41,649
STUDY DESIGN              Open Label; Dose Escalating
PROTOCOL DETAILS          STUDY INTENT: Maximum tolerated dose (MTD),
                          Pharmacokinetics, Drug safety, Drug
                          tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 32 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CMV infection. 3.
                          CD4 count < 150 cells/mm3 or < 15 percent
                          AND/OR quiescent CMV disease. 4. NO loss of
                          sight from CMV retinitis. 5. NO acute
                          opportunistic infection. 6. Life expectancy
                          at least to study completion. 7. Consent of
                          parent or guardian. NOTE: Infants < 6 months
                          of age at enrollment must have been >= 36
                          weeks gestational age at birth. NOTE:
                          Patients may co-enroll in other ACTG
                          protocols that do not involve the
                          administration of disallowed medications.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 150 cells/mm3. Or < 15
                          percent (required only if patients do not
                          have quiescent CMV disease). ( 0 - 100 ).
PATIENT AGE               AGE: 14 Days - 20 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 13 Days. 21 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 30 days
                          prior to study entry: G-CSF or GM-CSF.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Foscarnet. 2. Acyclovir. 3. Interferon. 4.
                          Myelotoxic agents for malignancy or other
                          condition. 5. Other agents with anti-CMV
                          activity. (NOTE: Enrollment of patients on
                          IVIG must be discussed with protocol chair).
                          6. Imipenem/cilastatin sodium.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Loss
                          of sight in one eye for any reason, with
                          evidence of CMV retinitis in the other eye.
                          2. Acute or chronic diarrhea that would
                          affect absorption. 3. Clinical or laboratory
                          toxicities of grade 3 or worse.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0018  Ganciclovir
MANUFACTURERS             Drug 1: Syntex Research 3401 Hillview
                          Avenue/PO Box 10850 Palo Alto, CA 94303
                          Contact: Drug Information (800) 444-4200.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Intravenous: 5 mg/kg
                          over 1 hr on day 1. Oral suspension: 10, 20,
                          30, or 40 mg in a single assigned doseday 3,
                          followed by the same dose q 8 hr beginning on
                          day 4 and continuing for a total of 24 weeks.
                          Optional oral capsules (offered if 6 patients
                          taking oral suspedose have AUC >= 4.3
                          mcg/ml/hr): given as a single dose on day a
                          dose equal to the suspension dose given on
                          day 3), followed bsame dose q 8 hr beginning
                          on day 6 and continuing for a total weeks
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous and oral;
                          10 ml vials, oral suspension, capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Short-term and long-term toxicity,
                          CMV retinitis and end organ disease.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Unacceptable
                          toxicity.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 or 4 neutropenia or
                          thrombocytopenia: Hold study drug. If
                          toxicity resolves to grade 2 within 14 days,
                          resume at original dose. If grade 3 or 4
                          neutropenia or thrombocytopenia recurs,
                          discontinue study drug permanently.
                          (Recurrence of neutropenia will not require
                          permanent discontinuation if ANC <= grade 2
                          toxicity can be maintained by G-CSF.) For
                          grade 3 or 4 nausea, vomiting, or diarrhea:
                          Hold study drug. If toxicity resolves to
                          grade 2 within 28 days, resume study drug at
                          original dose. For recurrent grade 3 or 4
                          nausea/vomiting/diarrhea, discontinue study
                          drug permanently. For other grade 3 or 4
                          toxicities: Discuss with protocol chair.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Ganciclovir/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/PHARMACOKINETICS
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
CAS REGISTRY NUMBER       82410-32-0 (Ganciclovir)
LAST REVISION DATE        941207
ENTRY MONTH               9411
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          941123 ACTU: 5048.
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 941102
                          ACTU: 4601.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 941123 ACTU:
                          7001.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 941103 ACTU: 4201.
MASSACHUSETTS             Children's Hosp of Boston / c/o Children's
                          Hosp AIDS Program 300 Longwood Avenue /
                          Carnegie Bldg / Third Floor Boston, MA 02115
                          Contact: Robert Bishop (617) 735-8198 OPEN
                          941130 ACTU: 2901.
PENNSYLVANIA              Saint Christopher's Hospital for Children /
                          Sect Imm & Rheum Erie Avenue at Front Street
                          Philadelphia, PA 19134-1095 Contact: Carole
                          Treston (215) 427-5284 Contact: FAX (215)
                          427-5555 OPEN 941115 ACTU: 6704.
 
40
UNIQUE IDENTIFIER         NIH/00495
PROTOCOL ID NUMBERS       NIAID ACTG 224
PROTOCOL TITLE            A Phase I/II Study of Recombinant
                          Interleukin-4 in AIDS and Kaposi's Sarcoma.
VERSION NUMBER & DATE     3 (940506)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Miles S
PROTOCOL CHAIRS           CO-CHAIR  Scadden D
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          tolerance of interleukin-4 (IL-4) in patients
                          with AIDS-related Kaposi's sarcoma. To
                          determine the effects of IL-4 on tumor growth
                          in patients with AIDS-related Kaposi's
                          sarcoma.
GENERAL DESCRIPTION       RATIONALE: IL-4 exhibits a variety of
                          beneficial effects on the immune system and
                          is a potent inhibitor of Kaposi's sarcoma
                          cells in vitro.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified
                          according to CD4 count and are enrolled in
                          cohorts of six patients at each of four dose
                          levels of IL-4 per strata. If patients at a
                          given dose level have received at least 2
                          weeks of study therapy and no more than two
                          patients experienced grade 3 or 4
                          drug-related toxicity, dose escalation in
                          subsequent patients may begin. The MTD is
                          defined as the dose at which 50 percent of
                          patients develop grade 3 or worse toxicity.
                          Patients must be on antiretroviral therapy
                          during study treatment
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Biopsy-proven AIDS-related
                          Kaposi's sarcoma (NOTE: Patients with
                          systemic pulmonary Kaposi's sarcoma or
                          documented Kaposi's sarcoma of the
                          gastrointestinal tract are not eligible). 2.
                          Serum HIV antibody positive, documented by
                          ELISA. 3. CD4 count <= 500 cells/mm3. 4. Must
                          be receiving some form of antiretroviral
                          therapy for at least 21 days prior to study
                          entry. 5. No active AIDS-related
                          opportunistic infections that require
                          induction therapy, such as Pneumocystis
                          carinii pneumonia (PCP), toxoplasma brain
                          abscess, cytomegalovirus retinitis or
                          colitis, cryptococcal meningitis, and
                          symptomatic Mycobacterium
                          avium-intracellulare (MAI). NOTE: Patients
                          with CD4 count >= 100 cells/mm3 may not have
                          any history of opportunistic infection.
                          Patients with CD4 count < 100 cells/mm3 and
                          stable opportunistic infections requiring
                          maintenance therapy are eligible at the
                          discretion of the investigator.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND BB4950
STUDY DESIGN              Open Label; Dose Escalating
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 64 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 52 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 15/64 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS-related Kaposi's sarcoma. 2.
                          HIV infection. 3. Current antiretroviral
                          therapy. 4. No active opportunistic
                          infections requiring induction therapy. 5.
                          Consent of parent or guardian if less than 18
                          years of age. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 500 cells/mm3. ( 0 -
                          100 - 200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: BUN <= 40 mg/dl. Lactate dehydrogenase
                          (LDH) or LDH1-2 isoenzymes within normal
                          limits. Creatine phosphokinase (CPK) or
                          CPK2(MB) isoenzymes within normal limits.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control /contraception during
                          the study and for 60 days after.
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Allowed: Radiation therapy
                          for Kaposi's sarcoma, to lesions other than
                          marker lesions.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Antiretroviral
                          therapy (AZT, ddI and/or ddC, d4T) for at
                          least 21 days prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required:
                          Antiretroviral therapy during study
                          treatment. Allowed: 1. Nonsteroidal
                          anti-inflammatory agents including
                          acetaminophen for drug-related fevers. 2.
                          Systemic steroids for no more than 1 week in
                          any 30-day period. 3. PCP prophylaxis with
                          TMP/SMX, dapsone, or inhaled pentamidine, if
                          patient has a history of PCP or a CD4 count <
                          250 cells/mm3. Allowed only in patients with
                          CD4 count < 100 cells/mm3: 1. Maintenance
                          doses of ganciclovir, pyrimethamine/sulfa and
                          TMP/SMX for stable, well-controlled
                          opportunistic infections. 2.
                          Non-myelosuppressive treatment IND
                          medications.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of myocardial infarction or
                          significant arrhythmias. 2. History of
                          symptomatic hypoglycemia. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 60 days after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Systemic therapy
                          (including chemotherapy, interferons, and
                          immune modulators) for Kaposi's sarcoma
                          within 4 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Chemotherapy, interferons, or immune
                          modulators for Kaposi's sarcoma. 2.
                          Myelosuppressive agents such as induction
                          doses of ganciclovir, Fansidar
                          (pyrimethamine/sulfadoxine), or any other
                          investigational drugs (with the exception of
                          non-myelosuppressive treatment IND
                          medications in specific patients). 3. GM-CSF
                          or erythropoietin (except for a second grade
                          3/4 neutropenia or anemia). 4. G-CSF.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Other
                          active malignancies (except basal cell
                          carcinoma of the skin and in situ cervical
                          cancer). 2. Alteration in mental status that
                          may prevent compliance. 3. Cardiac functional
                          capacity of Class II or worse OR regional
                          wall abnormalities or abnormal ejection
                          fraction on two-dimensional echocardiogram,
                          if performed.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0168  Interleukin-4
MANUFACTURERS             Drug 1: Schering-Plough Corporation 2000
                          Galloping Hill Road Kenilworth, NJ 07033
                          Contact: Dr Nicholas Pelliccione (908)
                          298-5680.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 0.5 - 4.0 mcg/kg/day
                          for 52 weeks, preferably early in the day and
                          at the same time q day
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 0.5 - 4.0 mcg/kg/day
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous
OTHER TREATMENT INFO.     TREATMENT DURATION: 52 weeks.
OTHER TREATMENT INFO.     END POINT: Dose-limiting toxicity,
                          progressive Kaposi's sarcoma, development of
                          an AIDS-defining opportunistic infection,
                          death.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Interruption of study drugs for
                          > 14 days. 3. Disease progression. 4.
                          Development of a new AIDS-defining
                          opportunistic infection. 5. Pregnancy. 6.
                          Patient noncompliance or desire to withdraw
                          from study. 7. Termination of study.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 noncardiac or
                          nonhematologic toxicity or grade 4
                          hematologic toxicity or fever attributable to
                          the study drug: Hold study drug until
                          toxicity resolves to baseline. If toxicity
                          resolves within 14 days, resume drug at 50
                          percent dose. If the same toxicity recurs,
                          discontinue study drug permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Interleukin-4/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*ETIOLOGY/
                          THERAPY
CAS REGISTRY NUMBER       0 (Interleukin-4)
LAST REVISION DATE        941207
ENTRY MONTH               9304
CALIFORNIA                University of California at Los Angeles
                          School of Medicine 60051 CHS / 10833 Le Conte
                          Avenue Los Angeles, CA 90024-1793 Contact:
                          Susan G McCarthy (310) 825-1301 OPEN 930602
                          ACTU: 0601.
MASSACHUSETTS             New England Deaconess Hospital 185 Pilgrim
                          Road Boston, MA 02215 Contact: Helen Fitch
                          (617) 735-0785 OPEN 930326 ACTU: 0103.
 
41
UNIQUE IDENTIFIER         NIH/00573
PROTOCOL ID NUMBERS       NIAID ACTG 223
PROTOCOL TITLE            A Phase II/III Prospective, Multicenter,
                          Randomized, Controlled Trial Comparing the
                          Safety and Efficacy of Three
                          Clarithromycin-Containing Combination Drug
                          Regimens for the Treatment of Disseminated
                          Mycobacterium avium Complex ( MAC ) Disease
                          in Persons With AIDS.
VERSION NUMBER & DATE     2 (940801)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Benson CA
PROTOCOL CHAIRS           CO-CHAIR  Chaisson RE, Currier JS
GENERAL DESCRIPTION       PURPOSE: To compare the efficacy and safety
                          of clarithromycin combined with rifabutin,
                          ethambutol, or both in the treatment of
                          disseminated Mycobacterium avium Complex
                          (MAC) disease in persons with AIDS, including
                          individuals who have or have not received
                          prior MAC prophylaxis.
GENERAL DESCRIPTION       RATIONALE: It is believed that effective
                          theapy for MAC disease in patients with AIDS
                          requires combinations of two or more
                          antimycobacterial agents in order to overcome
                          drug resistance and the unfavorable influence
                          of the profound immunosuppression associated
                          with AIDS. Data suggest that clarithromycin
                          may have substantial activity in two- or
                          three-drug combination regimens with
                          clofazimine, rifamycin derivatives,
                          ethambutol, or the 4-quinolones.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to one
                          of three treatment arms containing
                          clarithromycin in combination with
                          ethambutol, rifabutin, or both.
                          Clarithromycin alone is taken on days 1
                          through 3 to determine tolerance; the other
                          agents are added on day 4. Treatment
                          continues daily for 48 weeks. Patients with
                          complete or partial response at week 12
                          continue on their originally assigned regimen
                          for duration of therapy or until relapse.
                          Patients with treatment failure or relapse at
                          any time are rolled over to three-drug
                          salvage therapy with clarithromycin plus two
                          new drugs not previously received in their
                          original regimen, as follows:
                          rifabutin/clofazimine,
                          ethambutol/clofazimine, or
                          clofazimine/ciprofloxacin. Patients are
                          followed twice in the first week, then every
                          2 weeks for the first 2 months, then monthly
                          for the next 4 months, and then every 2
                          months thereafter until the end of 12 months.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (941207)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection. 2. Symptomatic
                          MAC disease with one blood culture positive
                          for MAC or AFB obtained within the past 90
                          days, or asymptomatic MAC disease defined by
                          two blood cultures positive for MAC or AFB
                          obtained at least 24 hours apart within the
                          past 90 days.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 43,856
STUDY DESIGN              Prospective; Multicenter; Randomized;
                          Controlled; Drug Combination; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 246 patients. (82 patients
                          in each of three study arms)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 48 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Disseminated MAC
                          disease. 3. Life expectancy of at least 8
                          weeks. NOTE: This protocol is approved for
                          prisoner participation. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 30 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral therapy. 2. Maintenance or
                          prophylactic therapy for other opportunistic
                          infections (with the exception of
                          specifically excluded drugs). 3.
                          Carbamazepine or theophylline. 4. Isoniazid
                          for TB prophylaxis.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of severe hypersensitivity to
                          erythromycin, clarithromycin, azithromycin,
                          ethambutol, rifampin, or rifabutin (including
                          Type 1 hypersensitivity reaction,
                          Stevens-Johnson syndrome, hepatitis, optic
                          neuritis, or exfoliative dermatitis). [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use barrier methods of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 1 week
                          prior to study entry: All antimycobacterial
                          drugs (other than isoniazid for TB
                          prophylaxis).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          antimycobacterial drugs (with the exception
                          of isoniazid for TB prophylaxis). 2. Therapy
                          for any acute infectious process other than
                          MAC. 3. Terfenadine or astemizole. 4. Active
                          treatment with fluconazole for more than 21
                          days (patients who are receiving fluconazole
                          for maintenance suppression of cryptococcal
                          meningitis and who have been on a stable dose
                          for 4 weeks or longer are permitted with
                          approval of the protocol chair). 5. Other
                          investigational drugs unless approved by
                          protocol chair.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Active
                          mycobacterial infection other than MAC that
                          requires treatment, with the exception of
                          isoniazid used solely for TB prophylaxis.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0099  Clarithromycin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0111  Ethambutol
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0085  Rifabutin
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0067  Clofazimine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0110  Ciprofloxacin
TRADE NAME OF SUBSTANCE   Drug 1 Biaxin
MANUFACTURERS             Drug 1: Abbott Laboratories One Abbott Park
                          Road Abbott Park, IL 60064 Contact: Dr J Carl
                          Craft (708) 937-8147.
MANUFACTURERS             Drug 2: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
MANUFACTURERS             Drug 3: Adria Laboratories Incorporated PO
                          Box 16529 Columbus, OH 43216-6529 Contact:
                          Beverly Wynne (614) 764-8307.
MANUFACTURERS             Drug 4: Ciba Pharmaceutical Company 556
                          Morris Avenue Summit, NJ 07901 Contact:
                          Medical Services Department (908) 277-5000.
MANUFACTURERS             Drug 5: Miles Incorporated Pharmaceutical
                          Division 400 Morgan Lane West Haven, CT
                          06516-4175 Contact: Professional Services
                          (800) 468-0894.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 500 mg BID for 48
                          weeks. Drug 2: 15 mg/kg daily for 48 weeks.
                          Drug 3: 450 mg daily for 48 weeks. Drug 4:
                          100 mg daily for 48 weeks. Drug 5: 750 mg BID
                          for 48 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1000 mg. Drug 2: 15
                          mg/kg. Drug 3: 450 mg. Drug 4: 100 mg. Drug
                          5: 1500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 500 mg tablets.
                          Drug 2: Oral, 400 mg tablets. Drug 3: Oral,
                          150 mg capsules. Drug 4: Oral, 100 mg
                          capsules. Drug 5: Oral, 500 and 750 mg
                          tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Response to treatment, time to
                          response, association of drug plasma
                          concentrations to changes in quantitative MAC
                          blood colony counts.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Requirement for treatment with
                          prohibited medications. 3. Relapse following
                          rollover to salvage regimen.
OTHER TREATMENT INFO.     MODIFICATION: Doses are reduced or
                          discontinued for specific toxicities.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Ciprofloxacin/*THERAPEUTIC USE
MESH HEADING              Clarithromycin/*THERAPEUTIC USE
MESH HEADING              Clofazimine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Rifabutin/*THERAPEUTIC USE
CAS REGISTRY NUMBER       2030-63-9 (Clofazimine)
CAS REGISTRY NUMBER       72559-06-9 (Rifabutin)
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       81103-11-9 (Clarithromycin)
CAS REGISTRY NUMBER       85721-33-1 (Ciprofloxacin)
LAST REVISION DATE        941207
ENTRY MONTH               9412
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 941123 ACTU: 5801.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941123 ACTU:
                          6104.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 941123 ACTU: 2701.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941123 ACTU: 2708.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 941123 ACTU: 2702.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02115 Contact: Sheila Hussey (617)
                          735-4103 OPEN 941123 ACTU: 0102.
MINNESOTA                 St Paul-Ramsey Medical Center 640 Jackson
                          Street St Paul, MN 55101 Contact: Ray Nelson
                          (612) 221-1280 OPEN 941205 ACTU: 1503.
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 941205 ACTU:
                          1501.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 941123 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 941123
                          ACTU: 2102.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          941128 ACTU: 3201.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 941123 ACTU: 0401.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 941123
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 941123 ACTU: 1901.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          941123 ACTU: 1102.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941123
                          ACTU: 2301.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 941123 ACTU: 6201.
 
42
UNIQUE IDENTIFIER         NIH/00469
PROTOCOL ID NUMBERS       NIAID ACTG 222
PROTOCOL TITLE            The Treatment of Pulmonary Mycobacterium
                          Tuberculosis in HIV Infection.
VERSION NUMBER & DATE     3 (940927)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To compare the efficacy and safety
                          of induction and continuation therapies for
                          the treatment of pulmonary tuberculosis (TB)
                          in HIV-infected patients who are either from
                          areas with known high rates of resistance to
                          one or more anti-TB drugs or from areas where
                          TB is expected to be susceptible to commonly
                          used anti-TB drugs.
GENERAL DESCRIPTION       RATIONALE: In some areas of the country,
                          resistance to one or more of the drugs
                          commonly used to treat TB has emerged. Thus,
                          the need to test regimens containing a new
                          drug exists. Furthermore, the optimal
                          duration of anti-TB therapy for HIV-infected
                          patients with TB needs to be determined.
GENERAL DESCRIPTION       METHODOLOGY: In the induction phase, patients
                          enrolled in drug-susceptible areas (defined
                          as metropolitan areas with a resistance rate
                          for isoniazid therapy of less than 10
                          percent) receive four drugs: isoniazid (plus
                          pyridoxine), rifampin, pyrazinamide, and
                          ethambutol. Patients enrolled in
                          drug-resistant areas (resistance rate for
                          isoniazid of 10 percent or higher) receive
                          the four-drug regimen with or without a fifth
                          drug, levofloxacin. After 8 weeks of
                          induction, patients with multi-drug
                          resistance are removed from study regimens;
                          all other patients enter a continuation
                          phase. Pansusceptible patients (showing
                          susceptibility to all first-line anti-TB
                          drugs) receive two study drugs for an
                          additional 18 or 31 weeks; patients with
                          isoniazid-resistant (or intolerant) TB
                          receive two or three study drugs for an
                          additional 44 weeks, while those with
                          rifampin-resistant TB receive two or three
                          study drugs for an additional 70 weeks.
                          Patients are evaluated every 2 weeks in the
                          induction phase and every 12 weeks in the
                          continuation phase. Minimum follow-up is 2
                          years.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Tuberculosis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: INDUCTION PHASE. 1. Working
                          diagnosis of HIV infection by medical and
                          behavioral histories, clinical signs and
                          symptoms, and laboratory tests. 2. Working
                          diagnosis of TB. CONTINUATION PHASE. 1.
                          Successful completion of induction phase and
                          confirmation of TB by culture and
                          susceptibility results. 2. Susceptible to and
                          tolerant of study drugs in the appropriate
                          continuation regimen. NOTE: Per 09/27/94
                          amendment, alternate entry criteria for the
                          continuation phase have been established as a
                          secondary recourse.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    CPCRA 019. IND 41,372
STUDY DESIGN              Multicenter; Randomized; Open Label;
                          Comparative; Prospective
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 650 patients. (450
                          patients in drug-resistant areas; 200
                          patients in drug-susceptible areas)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2-4 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 106/650 (941207).
PROTOCOL DETAILS          STUDY DURATION: Approximately 4 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 43 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: INDUCTION PHASE. 1. HIV infection. 2.
                          Diagnosis of pulmonary TB. NOTE: Patients
                          from susceptible areas may be 13 years of
                          age or older. Patients from resistant areas
                          must be 18 years of age or older.
                          CONTINUATION PHASE. 1. Successful completion
                          of induction phase and confirmation of TB by
                          culture and susceptibility results. 2.
                          Susceptibility to and tolerance of study
                          drugs in the appropriate continuation
                          regimen. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min. (if
                          creatinine value not available).
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: More than 3 weeks
                          of continuous anti-TB therapy immediately
                          prior to study entry, or more than 12 weeks
                          total of anti-TB therapy within the past 2
                          years.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Other
                          medications with anti-TB activity.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Multi-drug resistance to at least isoniazid
                          and rifampin or known to have had close
                          contact with a person with known multi-drug
                          resistant TB. 2. Known treatment-limiting
                          reaction to any of the study drugs. 3. Other
                          disorders or conditions for which the study
                          drugs are contraindicated.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0123  Isoniazid
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0109  Rifampin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0124  Pyrazinamide
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0111  Ethambutol
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0129  Levofloxacin
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0125  Pyridoxine
MANUFACTURERS             Drug 1: Schein Pharmaceuticals Incorporated /
                          Regulatory Affairs Mount Ebo Corporate Park /
                          Route 22 Brewster, NY 10509 Contact: Dr
                          William McIntyre (914) 278-3742.
MANUFACTURERS             Drug 2: Marion Merrell Dow Medical
                          Information / PO Box 9627 Kansas City, MO
                          64134-0627 Contact: Medical Information (800)
                          633-1610.
MANUFACTURERS             Drug 3: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
MANUFACTURERS             Drug 4: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
MANUFACTURERS             Drug 5: Ortho Pharmaceutical Corporation
                          Route 202 / PO Box 300 Raritan, NJ 08869-0602
                          Contact: Dr Vincent Ahonkha (908) 704-4991.
MANUFACTURERS             Drug 6: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: INDUCTION PHASE:
                          Resistant and susceptible areas - 300 mg
                          daily for 2 weeks, followed by 600 or 900 mg
                          thrice weekfor 6 weeks. CONTINUATION PHASE:
                          600 or 900 mg administered twice weekly for31
                          weeks in pansusceptible patients and for 70
                          weeks in rifampin-resistant/intolerant
                          patients (not administered in patwho are
                          isoniazid-resistant/intolerant). Drug 2:
                          INDUCTION PHASE: Resistant and
                          susceptible areas - 600 mg daily for 2
                          weeks, followed by 600 mg thrice weekly for
                          weeks. CONTINUATION PHASE: 600 mg twice
                          weekly for 44 weeks in patientare
                          pansusceptible or
                          isoniazid-resistant/intolerant (not
                          administered in those who are
                          rifampin-resistant/intolerant). Drug 3:
                          INDUCTION PHASE: Resistant and
                          susceptible areas - 2.0 g daily for 2
                          weeks, followed by 2.0 or 2.5 g thrice
                          weekly6 weeks. CONTINUATION PHASE: 3.0 or 3.5
                          g twice weekly for 70 weeks in
                          rifampin-resistant/intolerant patients who
                          received a four-druginduction regimen (not
                          administered in those who are
                          pansusceptisoniazid-resistant/intolerant, or
                          rifampin-resistant/intoleranthe five-drug
                          induction regimen). Drug 4: INDUCTION PHASE:
                          Resistant and susceptible areas - mg/kg
                          (maximum 2.4 g) daily for 2 weeks, followed
                          by 30 mg/kg (maximum 2.4 g) thrice weekly for
                          6 weeks. CONTINUATION PHASE: 50 mg/kg
                          (maximum 2.4 g) for 44 weeks in
                          isoniazid-resistant/intolerant patients and
                          70 weeks in in rifampin-resistant/intolerant
                          patients (not administered in patwith
                          pansusceptibility). Drug 5: INDUCTION PHASE:
                          Resistant areas only - 500 mg daily weeks,
                          followed by 750 mg thrice weekly for 6 weeks.
                          CONTINUATION PHASE: 750 mg twice weekly for
                          44 weeks in isoniazid-resistant/intolerant
                          patients who received the five-dinduction
                          regimen and for 70 weeks in
                          rifampin-resistant/intolepatients who
                          received the five-drug regimen (not
                          administered ipatients who received the
                          four-drug induction regimen). Drug 6:
                          INDUCTION PHASE: Resistant and
                          susceptible areas - daily for 2 weeks,
                          followed by 50 mg thrice weekly for 6 weeks
                          (administered with isoniazid). CONTINUATION
                          PHASE: 50 mg twice weekly in pansusceptible
                          and rifampin-resistant/intolerant patients
                          (no
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 300 mg (first 2 weeks
                          of induction). Drug 2: 450 or 600 mg (first 2
                          weeks of induction). Drug 3: 1.5 or 2.0 g
                          (first 2 weeks of induction). Drug 4: 20
                          mg/kg (first 2 weeks of induction). Drug 5:
                          500 mg (first 2 weeks of induction phase).
                          Drug 6: 50 mg (first 2 weeks of induction
                          phase)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 300 mg tablets.
                          Drug 2: Oral, 150 and 300 mg capsules. Drug
                          3: Oral, 500 mg tablets. Drug 4: Oral, 400 mg
                          tablets. Drug 5: Oral, 125 and 500 mg
                          tablets. Drug 6: Oral, 50 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 26-78 weeks.
OTHER TREATMENT INFO.     END POINT: Induction phase: Culture
                          conversion at 8 weeks. Continuation phase:
                          Failure while on therapy and relapse after
                          completion of therapy.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Development of
                          multi-drug resistance in induction phase. 2.
                          Failure to complete induction therapy within
                          10 weeks. 3. Unacceptable toxicity. 4. Not in
                          the patient's best interest to continue.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 toxicity: Hold
                          causative study drug, then restart at the
                          discretion of the primary physician. For
                          recurrent grade 3 or any grade 4 toxicity:
                          Hold study drugs temporarily; discontinue
                          permanently at the discretion of the primary
                          physician.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), National Institute of
                          Allergy & Infectious Diseases (CPCRA).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Ethambutol/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Isoniazid/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Ofloxacin/ANALOGS & DERIVATIVES/
                          ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
                          *THERAPEUTIC USE
MESH HEADING              Opportunistic Infections/COMPLICATIONS/DRUG
                          THERAPY
MESH HEADING              Pyrazinamide/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Pyridoxine/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Rifampin/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Tuberculosis, Pulmonary/COMPLICATIONS/*DRUG
                          THERAPY
CAS REGISTRY NUMBER       13292-46-1 (Rifampin)
CAS REGISTRY NUMBER       54-85-3 (Isoniazid)
CAS REGISTRY NUMBER       65-23-6 (Pyridoxine)
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       82419-36-1 (Ofloxacin)
CAS REGISTRY NUMBER       98-96-4 (Pyrazinamide)
LAST REVISION DATE        941207
ENTRY MONTH               9304
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          940311 ACTU: 1201.
COLORADO                  Denver / CPCRA 605 Bannock Street Denver, CO
                          80204-4507 Contact: Jack Rouff (303) 436-7184
                          Contact: (303) 436-7224 OPEN 930609.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 930715 ACTU: 6401.
DISTRICT OF COLUMBIA      Howard U Coll of Med / AIDS Minority
                          Infrastructure Program 2112 Georgia Avenue NW
                          Washington, DC 20059 Contact: Victoria Holly
                          -Trimmer (202) 806-4700 Contact: (202)
                          806-4755 OPEN 931130 ACTU: 5301.
DISTRICT OF COLUMBIA      Washington Regional AIDS Program 50 Irving St
                          N W / Room ID-151B Washington, DC 20422
                          Contact: John Scott (202) 745-8695 OPEN
                          930405.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 930607
                          ACTU: 0901.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 930610
                          ACTU: 5201.
ILLINOIS                  Cook County Hospital Passavant Pavilion /
                          Room 823 / 303 East Superior Chicago, IL
                          60611 Contact: Baiba L Berzins (312) 908-9636
                          OPEN 930716 ACTU: 2705.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 940513 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 940513 ACTU:
                          0202.
MICHIGAN                  Comprehensive AIDS Alliance of Detroit 4160
                          John R / Harper Hospital Prof Bldg / Suite
                          202 Detroit, MI 48201 Contact: Constance
                          Rowley (313) 993-0934 OPEN 940216.
MICHIGAN                  Henry Ford Hospital 2799 West Grand Boulevard
                          Detroit, MI 48202 Contact: Diane Mastro-Polak
                          (313) 876-7664 OPEN 930618.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 930405 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 930412 ACTU: 0401.
NEW YORK                  St Clare's Hospital and Health Center 415
                          West 51st Street New York, NY 10019 Contact:
                          Phyllis Ristau (212) 459-8449 OPEN 940427
                          ACTU: 2204.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          930721 ACTU: 2201.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          930412 ACTU: 1801.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 931207 ACTU: 7501.
NEW YORK                  Harlem AIDS Treatment Group Harlem Hospital /
                          Women's Pavilion Room 126 New York, NY 10037
                          Contact: Joshua Standig (212) 939-2951 OPEN
                          930405.
NEW YORK                  Bronx-Lebanon Hospital Center 1309 Fulton
                          Avenue Bronx, NY 10456 Contact: Cathy Pollard
                          (718) 293-2593 Contact: (718) 901-8916 OPEN
                          930405.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 930405 ACTU:
                          1905.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 930405
                          ACTU: 1902.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 930405 ACTU: 1903.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 930405
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 930405
                          ACTU: 1904.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 930405 ACTU: 1901.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 930405 ACTU: 1906.
NEW YORK                  North Central Bronx Hospital / Samaritan
                          Village Inc 418 Forchheimer ID / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 930405 ACTU: 1907.
NEW YORK                  Montefiore Medical Center / Adolescent AIDS
                          Program 111 East 210th Street / NW674 Bronx,
                          NY 10467 Contact: Dina Monte (718) 882-0023
                          OPEN 930405 ACTU: 4903.
NEW YORK                  Bronx Veterans Administration Medical Center
                          130 West Kingsbridge Road Bronx, NY 10468
                          Contact: Nancy Ostrow (718) 584-9000 X
                          667Contact: (718) 584-9000 X 667OPEN 930519
                          ACTU: 1804.
NEW YORK                  Addiction Research And Treatment Corporation
                          22 Chapel Street Brooklyn, NY 11201 Contact:
                          Dr Robert Sawyer (718) 260-2917 OPEN 930707.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 930405
                          ACTU: 5901.
NEW YORK                  Clinical Directors Network of Region II 5601
                          2nd Avenue #3 Brooklyn, NY 11220 Contact:
                          Linda Podhurst (212) 255-3841 OPEN 930405.
NEW YORK                  City Hospital at Elmhurst / Mt Sinai 79-01
                          Broadway Room D1-29 Elmhurst, NY 11373
                          Contact: Dinah Reitman (718) 334-3963 OPEN
                          940706 ACTU: 1803.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930722 ACTU: 7403.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930722 ACTU: 7402.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 930722 ACTU: 7401.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          930602 ACTU: 1102.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 931001 ACTU:
                          2401.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 940720 ACTU: 6201.
 
43
UNIQUE IDENTIFIER         NIH/00533
PROTOCOL ID NUMBERS       NIAID ACTG 221
PROTOCOL TITLE            A Phase I/II Study of Delayed-Type
                          Hypersensitivity (DTH) Reactions to
                          Intradermal HIV Envelope Antigen.
VERSION NUMBER & DATE     4 (941027)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Katzenstein D
GENERAL DESCRIPTION       PURPOSE: To determine the frequency of
                          delayed-type hypersensitivity (DTH) reactions
                          in HIV-positive patients to two doses of two
                          envelope glycoprotein antigens prepared
                          differently. To determine whether patients
                          who have previously demonstrated a DTH
                          response to intradermal MGStage HIV-1 gp160
                          IIIB baculovirus (MicroGeneSys) have a
                          reproducible response to a repeat injection
                          of gp160 and whether there is
                          cross-reactivity to intradermal HIV-1 rgp160
                          IIIB vero cell expressed (Immuno-AG).
GENERAL DESCRIPTION       RATIONALE: Previous studies in individuals
                          immunized with gp160 suggest that a skin test
                          response in immunized patients can be used as
                          a surrogate marker for new proliferative and
                          cytotoxic responses induced by vaccination.
GENERAL DESCRIPTION       METHODOLOGY: Patients are stratified into
                          three groups. Fifteen patients who are not on
                          antiretroviral therapy and received prior
                          MicroGeneSys gp160 antigen in ACTG 137
                          (stratum 1) will receive intradermal
                          injections of Immuno-AG gp160 IIIB in one
                          arm, followed 1 week later by intradermal
                          injections of MicroGeneSys gp160 IIIB antigen
                          in the opposite arm. Twenty patients who are
                          not on antiretroviral therapy and not
                          previously immunized with gp160 (stratum 2),
                          as well as 20 other patients who are
                          currently on antiretroviral therapy with
                          zidovudine, didanosine, dideoxycytidine, or
                          stavudine and not previously immunized with
                          gp160 (stratum 3), will receive intradermal
                          injections of Immuno-AG gp160 IIIB in one arm
                          simultaneously with MicroGeneSys gp160 IIIB
                          in the opposite arm. All patients return 48
                          hours after each injection session for skin
                          test reading.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA and
                          Western blot, culture, PCR, or p24 antigen.
                          2. CD4 count >= 400 cells/mm3 within 90 days
                          prior to study entry. 3. NO current active
                          opportunistic infection or neoplasm (other
                          than cutaneous Kaposi's sarcoma that is
                          stable with < 10 lesions).
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND BB5177
STUDY DESIGN              Blinded; Comparative
PROTOCOL DETAILS          STUDY INTENT: Immunology, Adverse effects.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 55 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 1-2 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 37/55 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count >= 400 cells/mm3. 3. NO current active
                          opportunistic infection or neoplasm (other
                          than stable cutaneous Kaposi's sarcoma).
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 400 cells/mm3. ( 400
                          - 500 - 600 - 700 - 800 - plus ).
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 30 days
                          prior to study entry: 1. Any antiretroviral
                          drugs (other than AZT, ddI, ddC, or d4T for
                          patients in stratum 3). 2. Systemic
                          corticosteroids, topical corticosteroids on
                          the arms, or other systemic immunosuppressant
                          agents or antineoplastic agents. Excluded
                          within 72 hours prior to intradermal
                          injections: Antihistamine or
                          anti-inflammatory medications.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antihistamine or anti-inflammatory
                          medications for the 48-hour period between
                          injection and skin test reading. 2. Topical
                          steroids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Known
                          hypersensitivity to insect proteins.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0041  gp160 Vaccine
                          (MicroGeneSys)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0162  gp160 Vaccine (Immuno-AG)
MANUFACTURERS             Drug 1: MicroGeneSys Incorporated 1000
                          Research Parkway Meridan, CT 06450-7159
                          Contact: Frank Volvovitz (203) 686-0800.
MANUFACTURERS             Drug 2: Immuno-US Incorporated / Media
                          Information Office c/o Cooney/Waters Group /
                          99 Park Avenue / Suite 25 New York, NY 10016
                          Contact: Sherri Michelstein (212) 557-7111.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 and 10 mcg in one
                          arm (administered 1 week prior to
                          MicroGeneSys gp160 antigen OR simultaneously
                          with MicroGeneSys antigen). Drug 2: 1 and 10
                          mcg in one arm (administered sequentially one
                          after Immuno-AG gp160 antigen OR
                          simultaneously with Immuno-AG antigen)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intradermal injection.
                          Drug 2: Intradermal injection
OTHER TREATMENT INFO.     END POINT: DTH reaction 48 hours after
                          injections.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Gene Products, env/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*IMMUNOLOGY
MESH HEADING              HIV Antigens/*IMMUNOLOGY
MESH HEADING              HIV Infections/*THERAPY
MESH HEADING              HIV-1/*IMMUNOLOGY
MESH HEADING              Human
MESH HEADING              Hypersensitivity, Delayed
MESH HEADING              Injections, Intradermal
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Protein Precursors/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*IMMUNOLOGY
MESH HEADING              Vaccines, Synthetic
CAS REGISTRY NUMBER       0 (HIV Antigens)
CAS REGISTRY NUMBER       0 (HIV envelope protein gp160)
CAS REGISTRY NUMBER       0 (Vaccines, Synthetic)
LAST REVISION DATE        941207
ENTRY MONTH               9405
CALIFORNIA                AIDS Community Research Consortium 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harris (415) 364-5653 OPEN
                          940824 ACTU: 0505.
CALIFORNIA                Santa Clara Valley Med Ctr / ACRC 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harriss (415) 364-5653 OPEN
                          941019 ACTU: 0506.
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 940824
                          ACTU: 0501.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 940824 ACTU: 0401.
 
44
UNIQUE IDENTIFIER         NIH/00527
PROTOCOL ID NUMBERS       NIAID ACTG 220
PROTOCOL TITLE            A Pre-Enrollment Protocol for HIV-Infected
                          Adolescents.
VERSION NUMBER & DATE     1 (930519)
TRIAL CATEGORY            Epidemiology
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  D'Angelo LJ
PROTOCOL CHAIRS           CO-CHAIR  Futterman D, Abdalian S
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To identify, characterize,
                          and co-enroll HIV-infected adolescents into
                          existing and future ACTG (or other
                          NIH-sponsored) HIV treatment protocols
                          through the systematic and recurrent
                          assessment of eligibility. To assess the
                          ability of adolescents enrolled in ACTG 220
                          to adhere to ACTG (or other NIH-sponsored)
                          HIV treatment protocols; and to define
                          factors that influence the adolescent's
                          ability to enter or adhere to study
                          protocols. SECONDARY: To describe the nature,
                          stage, and progression of HIV infection in
                          adolescents.
GENERAL DESCRIPTION       RATIONALE: Little is known about HIV-infected
                          adolescents as a group and, as a result,
                          small numbers of them are currently enrolled
                          in ACTG drug studies. Creative approaches are
                          needed to encourage enrollment of
                          HIV-infected adolescents whose
                          socio-demographic profile has made access to
                          NIH-sponsored research unlikely.
GENERAL DESCRIPTION       METHODOLOGY: At entry and at every subsequent
                          visit, participants are systematically
                          evaluated for eligibility and willingness to
                          enter ACTG (or other NIH-sponsored) HIV
                          treatment protocols from a menu developed and
                          updated by the Pediatric Adolescent Working
                          Group of the ACTG. A survey of participant
                          attitudes, behaviors, and beliefs is
                          administered and updated semiannually.
                          Participants attend clinic visits every 3
                          months and are followed for a minimum of 6
                          months, until the end of the study. They
                          receive periodic physical exams, STD and
                          gynecologic or genitourinary evaluations, HIV
                          symptom assessment and related diagnoses, TB
                          evaluation, and laboratory tests (hematology
                          and immunology).
PROTOCOL PHASE            Epidemiology
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Participants meet the following criteria:
                          Laboratory evidence of HIV infection
                          (positive HIV antibody test with standard
                          confirmatory tests).
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Prospective
PROTOCOL DETAILS          STUDY INTENT: Epidemiology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 250 patients. 0
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 6
                          months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 161/250 (941207).
PROTOCOL DETAILS          STUDY DURATION: 4 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 46 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants must
                          meet the following criteria: 1. HIV
                          infection. 2. NOT currently enrolled in an
                          ACTG treatment protocol. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: Non-applicable percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: Non-applicable g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: Non-applicable cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: Non-applicable platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CD4/CD8 RATION: Non-applicable.
PATIENT INCLUSION CRIT.   BILIRUBIN: Non-applicable mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): Non-applicable.
PATIENT INCLUSION CRIT.   SGPT(ALT): Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE: Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: Non-applicable ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: Non-applicable.
PATIENT AGE               AGE: 13 Years - 20 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years. 21 Years - 99 Years.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Participants with the
                          following condition are excluded: No legal
                          provision for consent to participate in
                          clinical research can be determined.
PATIENT EXCLUSION CRIT.   AVAILABILITY: No access to or ability to be
                          followed at a participating ACTG site.
OTHER TREATMENT INFO.     END POINT: Co-enrollment of patient in ACTG
                          (or other NIH-sponsored) HIV treatment
                          protocol(s); demonstration of patient
                          adherence with the requirements of ACTG 220;
                          identification of factors that interfere with
                          patient adherence to study protocol(s).
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Adolescence
MESH HEADING              Adolescent Behavior
MESH HEADING              Female
MESH HEADING              HIV Infections/*EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Human
MESH HEADING              Male
LAST REVISION DATE        941207
ENTRY MONTH               9311
ALABAMA                   University of Alabama at Birmingham School of
                          Medicine 751 CHT / University Station
                          Birmingham, AL 35294 Contact: Michael Cooney
                          (205) 939-9552 Contact: beeper (205) 869-9524
                          OPEN 930831 ACTU: 5046.
CALIFORNIA                UCLA Medical Center / Pediatrics 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          931118 ACTU: 3601.
CALIFORNIA                Children's Hospital of Los Angeles 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1757
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          940427 ACTU: 3602.
CALIFORNIA                Children's Hospital of Los Angeles /
                          Children's AIDS Center 4650 Sunset Blvd /
                          Mail Stop #54 Los Angeles, CA 90027 Contact:
                          Antonieta Sosa (213) 669-2180 OPEN 940606
                          ACTU: 9916.
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          940413 ACTU: 5048.
CALIFORNIA                UCSF / Moffitt Hospital 602 / Pediatrics 505
                          Parnassus / Box 0105 San Francisco, CA
                          94143-0105 Contact: Debbie Trevithick (415)
                          476-6480 OPEN 930930 ACTU: 4501.
CALIFORNIA                Children's Hospital Oakland 747 Fifty Second
                          Street Oakland, CA 94609-1809 Contact: Jim
                          Riddel (510) 428-3000 X 282Contact: (510)
                          539-6311 X PagOPEN 930729 ACTU: 4504.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 931004 ACTU:
                          7001.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 931014 ACTU: 5701.
DISTRICT OF COLUMBIA      Children's National Medical Center / Special
                          Immuno Svc Suite 2108 / 111 Michigan Avenue
                          NW Washington, DC 20010-2970 Contact: Sandra
                          Jones (202) 884-3682 OPEN 930726 ACTU: 7101.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 940824 ACTU: 4201.
GEORGIA                   Emory University Hospital 69 Butler Street SE
                          Atlanta, GA 30303 Contact: Judy Sarver (404)
                          616-6227 Contact: clinic (404) 616-4390
                          Contact: beeper (404) 899-5290 OPEN 931020
                          ACTU: 5030.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 940405 ACTU: 4001.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 931109 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 930729 ACTU: 7201.
MASSACHUSETTS             Children's Hosp of Boston / c/o Children's
                          Hosp AIDS Program 300 Longwood Avenue /
                          Carnegie Bldg / Third Floor Boston, MA 02115
                          Contact: Robert Bishop (617) 735-8198 OPEN
                          931208 ACTU: 2901.
MASSACHUSETTS             Boston City Hospital / Ped Infect Dis /
                          Finland Lab 774 Albany Street / Finland Lab
                          Room 301 Boston, MA 02118 Contact: Anne Marie
                          Reagan (617) 534-5813 OPEN 940304 ACTU: 2903.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 930708 ACTU:
                          4701.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Frances Tennant (402) 559-5750 OPEN
                          940919 ACTU: 1505.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue / Pediatric
                          New York, NY 10016 Contact: Nagamah Deygoo
                          (212) 263-6426 OPEN 930824 ACTU: 4401.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 ACTU:
                          1801.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940824 ACTU:
                          4301.
NEW YORK                  Harlem Hospital 506 Lenox Avenue New York, NY
                          10037 Contact: Rick Urbano (212) 939-4040
                          Contact: (212) 939-4045 OPEN 931215 ACTU:
                          5006.
NEW YORK                  Bronx Lebanon Hospital Center / Department of
                          Pediatrics 1650 Selwyn Avenue Room 2C Bronx,
                          NY 10457 Contact: Patrice Edwards-Cihak (718)
                          960-1015 OPEN 931022 ACTU: 6901.
NEW YORK                  Montefiore Medical Center / Adolescent AIDS
                          Program 111 East 210th Street / NW674 Bronx,
                          NY 10467 Contact: Dina Monte (718) 882-0023
                          OPEN 930726 ACTU: 4903.
NEW YORK                  Montefiore Medical Center Adolescent AIDS
                          Program 111 East 210th Street Bronx, NY
                          10467-2490 Contact: Dina Monte (718) 882-0023
                          OPEN 930812 ACTU: 5049.
NEW YORK                  Westchester Hospital / New York Medical
                          College Munger Pavillion Room 134 Valhalla,
                          NY 10595 Contact: Liz Ahern (914) 285-7898
                          Contact: (914) 993-4643 OPEN 940606 ACTU:
                          5005.
NEW YORK                  Schneider Children's Hospital / Long Island
                          Jewish Med Ctr 270-05 76th Avenue Room 235 /
                          Div of Allergy and Immunology New Hyde Park,
                          NY 11042 Contact: Debby Hickey (718) 470-3300
                          OPEN 930824 ACTU: 5001.
NEW YORK                  King's County Hospital Center / SUNY HSCB 450
                          Clarkson Avenue Brooklyn, NY 11203 Contact:
                          Helen Bergin (718) 245-3342 Contact: (718)
                          245-3341 Contact: (718) 245-4485 OPEN 940301
                          ACTU: 5035.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          940415 ACTU: 1102.
NEW YORK                  Children's Hospital 219 Bryant Street
                          Buffalo, NY 14222 Contact: Cynthia Kelly
                          (716) 878-7908 OPEN 940303 ACTU: 1104.
OHIO                      Children's Hospital 700 Children's Drive
                          Columbus, OH 43205-2696 Contact: Jane Hunkler
                          (614) 722-4460 Contact: (614) 722-6050 OPEN
                          940728 ACTU: 2302.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 940323 ACTU:
                          2401.
OHIO                      Childrens Hospital of Cincinnati Eden and
                          Bethesda Avenue Cincinnati, OH 45267-0405
                          Contact: Jill Leonard (513) 558-6977 OPEN
                          940330 ACTU: 2404.
OTHER                     Ramon Ruiz Arnau University Hospital Laurel
                          Avenue Bayamon, PR 00619 Contact: Leticia
                          Diaz (809) 798-2733 OPEN 931028 ACTU: 5033.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 940317 ACTU: 5031.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          940308 ACTU: 6601.
PENNSYLVANIA              Milton S Hershey Medical Center / Hemophilia
                          Cntr of W Penn 812 Fifth Avenue Pittsburgh,
                          PA 15219 Contact: Dr Margaret V Ragni (412)
                          622-7270 OPEN 940513 ACTU: 9318.
PENNSYLVANIA              George Washington University(Hershey
                          Satellite) 500 University Drive Post Office
                          Box 850 Hershey, PA 17033-0850 Contact: Dr
                          Fran Damianos (717) 531-7488 OPEN 940711.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 931118 ACTU: 6701.
SOUTH CAROLINA            Medical University of South Carolina Clinical
                          Science Building / 171 Ashley Avenue
                          Charleston, SC 29425-3312 Contact: Genny
                          Connelly (803) 792-2385 OPEN 931207 ACTU:
                          5037.
 
45
UNIQUE IDENTIFIER         NIH/00554
PROTOCOL ID NUMBERS       NIAID ACTG 219
PROTOCOL TITLE            Pediatric Late Outcomes Protocol.
VERSION NUMBER & DATE     1 (930121)
TRIAL CATEGORY            Epidemiology
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Oleske J
PROTOCOL CHAIRS           CO-CHAIR  Fowler MG
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To describe late outcomes
                          (long-term consequences related to HIV
                          disease progression, treatment effects, and
                          interaction of HIV disease and therapy) in
                          HIV-infected infants, children, and
                          adolescents currently or previously enrolled
                          in pediatric ACTG protocols; and to evaluate
                          late treatment effects in these children. To
                          determine whether infants born to
                          HIV-infected women who were enrolled in ACTG
                          protocols while pregnant demonstrate any late
                          treatment effects (late consequences of
                          antiretroviral therapy received in utero
                          and/or in the newborn period). SECONDARY: To
                          provide data describing the demographic,
                          medical, and treatment characteristics of
                          children enrolled in ACTG clinical trials.
GENERAL DESCRIPTION       RATIONALE: The potential long-term benefits,
                          toxicities, and other adverse outcomes of new
                          anti-HIV therapies cannot currently be
                          assessed within the time frame of clinical
                          trials underway. The need exists to better
                          assess both positive and negative late
                          outcomes and late treatment effects in
                          children who are still growing.
GENERAL DESCRIPTION       METHODOLOGY: Children have a complete
                          physical exam, history, Tanner staging
                          growth, neurologic exam, and quality-of-life
                          assessment every 6 months (if < 3 years of
                          age) or every 12 months (if >= 3 years of
                          age). Laboratory tests (hematology,
                          chemistries, urinalysis, etc.) are also
                          performed every 6 or 12 months (according to
                          age) in infected individuals and every 6
                          months or 3 years in uninfected individuals.
                          Audiometry is performed at ages 6 and 12. EKG
                          and ophthalmic exams are performed at
                          specified intervals. Participants are
                          followed until age 21 or until lost to
                          follow-up.
PROTOCOL PHASE            Epidemiology
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Participants must meet at least one of the
                          following criteria: 1. Infant born to an
                          HIV-infected woman who is currently enrolled
                          or has been enrolled in an ACTG perinatal
                          transmission or
                          antiretroviral/immunomodulator therapy
                          protocol while pregnant with this child. 2.
                          HIV-infected infant, child, or adolescent who
                          - has currently or previously enrolled in an
                          ACTG treatment protocol OR - was discontinued
                          from an ACTG treatment or perinatal
                          transmission protocol because of toxicity OR
                          - was enrolled in a protocol but never
                          received study drug.
ELIGIBILITY               ASYM. ARC. AIDS. HIV Seronegative / OTHER.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Prospective
PROTOCOL DETAILS          STUDY INTENT: Epidemiology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 1200 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until age 21 or
                          lost to follow-up.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1076/1200 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 74 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants must
                          meet at least one of the following criteria:
                          1. HIV-infected infant, child, or adolescent
                          currently or previously enrolled in an ACTG
                          treatment protocol. 2. Infant born to an
                          HIV-infected woman who is currently enrolled
                          or has been enrolled in an ACTG perinatal
                          transmission or
                          antiretroviral/immunomodulator therapy
                          protocol while pregnant with this child.
                          NOTE: Children and adolescents enrolled
                          solely in ACTG 220 (pre-enrollment protocol)
                          or other observational studies are not
                          eligible for this protocol until they become
                          enrolled in an ACTG treatment trial (adult,
                          perinatal, or pediatric). [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: Non-applicable percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: Non-applicable g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: Non-applicable cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: Non-applicable platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CD4/CD8 RATION: Non-applicable.
PATIENT INCLUSION CRIT.   BILIRUBIN: Non-applicable mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): Non-applicable.
PATIENT INCLUSION CRIT.   SGPT(ALT): Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE: Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: Non-applicable ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: Non-applicable.
PATIENT AGE               AGE: 01 Days - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Non-applicable.
OTHER TREATMENT INFO.     END POINT: Patient late outcomes, including
                          survival, growth, nutrition, quality of life,
                          neurologic and neuropsychologic parameters,
                          organ system toxicities, AIDS-defining
                          opportunistic infections or cancer, and
                          immunologic and virologic parameters.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Adolescence
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              HIV Infections/*EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
LAST REVISION DATE        941207
ENTRY MONTH               9310
ALABAMA                   University of Alabama at Birmingham School of
                          Medicine 751 CHT / University Station
                          Birmingham, AL 35294 Contact: Michael Cooney
                          (205) 939-9552 Contact: beeper (205) 869-9524
                          OPEN 930714 ACTU: 5046.
CALIFORNIA                Harbor General / UCLA Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 930824 ACTU: 3609.
CALIFORNIA                UCLA Medical Center / Pediatrics 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          930408 ACTU: 3601.
CALIFORNIA                Long Beach Memorial Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 930609 ACTU: 3606.
CALIFORNIA                Cedars Sinai Medical Center / Pediatrics 8700
                          Beverly Boulevard Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          930802 ACTU: 3603.
CALIFORNIA                Children's Hospital of Los Angeles 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1757
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          940627 ACTU: 3602.
CALIFORNIA                Children's Hospital of Los Angeles /
                          Children's AIDS Center 4650 Sunset Blvd /
                          Mail Stop #54 Los Angeles, CA 90027 Contact:
                          Antonieta Sosa (213) 669-2180 OPEN 940308
                          ACTU: 9916.
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          930430 ACTU: 5048.
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 930616
                          ACTU: 4601.
CALIFORNIA                Fountain Valley Regional Hospital and Medical
                          Center 17150 Euclid Avenue / Suite 322
                          Fountain Valley, CA 92708 Contact: Dr Douglas
                          Cable (714) 432-0422 OPEN 931028.
CALIFORNIA                UCSF / Moffitt Hospital 602 / Pediatrics 505
                          Parnassus / Box 0105 San Francisco, CA
                          94143-0105 Contact: Debbie Trevithick (415)
                          476-6480 OPEN 930824 ACTU: 4501.
CALIFORNIA                San Francisco General Hospital (Pediatric)
                          Box 0105 Moffitt Hospital 602 / 505 Parnassus
                          San Francisco, CA 94143-0105 Contact: Debbie
                          Trevithick (415) 476-6480 OPEN 930824 ACTU:
                          4502.
CALIFORNIA                Children's Hospital Oakland 747 Fifty Second
                          Street Oakland, CA 94609-1809 Contact: Jim
                          Riddel (510) 428-3000 X 282Contact: (510)
                          539-6311 X PagOPEN 930709 ACTU: 4504.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 930719 ACTU:
                          7001.
CONNECTICUT               Univ of Connecticut Farmington / Univ of CT
                          Health Center 263 Farmington Avenue
                          Farmington, CT 06032 Contact: Lorraine Wells
                          (203) 679-2320 OPEN 940214 ACTU: 7303.
CONNECTICUT               Yale University School of Medicine PO Box
                          3333 / 333 Cedar Street New Haven, CT
                          06510-8064 Contact: Unspecified (203)
                          737-4040 OPEN 940119 ACTU: 5038.
DISTRICT OF COLUMBIA      Georgetown University Hospital / PC 3800
                          Reservoir Road NW / Second Floor Washington,
                          DC 20007-2197 Contact: Maureen Dwyer (202)
                          687-5437 OPEN 931221 ACTU: 7104.
DISTRICT OF COLUMBIA      Children's National Medical Center / Special
                          Immuno Svc Suite 2108 / 111 Michigan Avenue
                          NW Washington, DC 20010-2970 Contact: Sandra
                          Jones (202) 884-3682 OPEN 930607 ACTU: 7101.
DISTRICT OF COLUMBIA      Howard University Hospital 2041 Georgia
                          Avenue NW Washington, DC 20060 Contact: Dr
                          Helga Finke (202) 865-1248 OPEN 930729 ACTU:
                          5044.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 930514 ACTU: 4201.
GEORGIA                   Emory University Hospital 69 Butler Street SE
                          Atlanta, GA 30303 Contact: Judy Sarver (404)
                          616-6227 Contact: clinic (404) 616-4390
                          Contact: beeper (404) 899-5290 OPEN 930430
                          ACTU: 5030.
ILLINOIS                  University of Illinois at Chicago 840 S Wood
                          Street Chicago, IL 60612 Contact: Patricia
                          Naughton (312) 996-1778 OPEN 930910 ACTU:
                          5028.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 930520 ACTU: 4001.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 940718 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 930831 ACTU: 7201.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street / SHU-Main 3
                          Springfield, MA 01199 Contact: MaryPat Toye
                          (413) 784-5399 OPEN 930609 ACTU: 7302.
MASSACHUSETTS             University of Massachusetts Medical School /
                          Dept of Peds 55 Lake Avenue North Worcester,
                          MA 01655-0001 Contact: Joanne Shepard (508)
                          856-1692 OPEN 931213 ACTU: 7301.
MASSACHUSETTS             Children's Hospital 300 Longwood Avenue /
                          Carnegie 3 Boston, MA 02115 Contact: Robert
                          Bishop (617) 735-8198 OPEN 930802 ACTU: 2901.
MASSACHUSETTS             Boston City Hospital / Ped Infect Dis /
                          Finland Lab 774 Albany Street / Finland Lab
                          Room 301 Boston, MA 02118 Contact: Anne Marie
                          Reagan (617) 534-5813 OPEN 940304 ACTU: 2903.
MARYLAND                  University of Maryland School of Medicine /
                          Pediatrics 120 Penn Street Baltimore, MD
                          21201 Contact: Sue Lovelace (410) 706-8220
                          OPEN 940124 ACTU: 3702.
MARYLAND                  The Johns Hopkins University ( Pediatrics )
                          600 North Wolfe Street Baltimore, MD 21287
                          Contact: Laura J Belcher (410) 955-9749 OPEN
                          940405 ACTU: 3701.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Charnell
                          Cromer (313) 745-5565 OPEN 931118 ACTU: 5041.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          940124 ACTU: 3201.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 930708 ACTU:
                          4701.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 930616 ACTU: 2801.
NEW JERSEY                Univ of Med & Dentistry of NJ / Univ Hospital
                          15 South Ninth Street Newark, NJ 07107-2198
                          Contact: George Donavan Mcsherry (201)
                          268-8273 OPEN 931227 ACTU: 2802.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          Ninth Street Newark, NJ 07107-2198 Contact:
                          George Donavan McSherry (201) 268-8273 OPEN
                          940304 ACTU: 2803.
NEW JERSEY                Robert Wood Johnson University Hospital /
                          UMDNJ One Robert Wood Johnson Place CN19 New
                          Brunswick, NJ 08903-0019 Contact: Ida Kechula
                          (908) 937-7894 OPEN 940610 ACTU: 5032.
NEW YORK                  Beth Israel Medical Center / Pediatrics First
                          Avenue at 16th Street Dazian Pavilion Tenth
                          Floor New York, NY 10003 Contact: Ann Marshak
                          (212) 420-4432 OPEN 930611 ACTU: 4302.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue / Pediatric
                          New York, NY 10016 Contact: Nagamah Deygoo
                          (212) 263-6426 OPEN 930412 ACTU: 4401.
NEW YORK                  Cornell Medical Center N-834 / Pediatric
                          Infectious Disease 1300 York Avenue New York,
                          NY 10021 Contact: Tony Hinds (212) 746-3326
                          OPEN 940114 ACTU: 5019.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 ACTU:
                          1801.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940114 ACTU:
                          4301.
NEW YORK                  Mount Sinai / Hemophilia Treatment Center One
                          Gustave Levy Place New York, NY 10029
                          Contact: Avril Gabriel (212) 241-0236 OPEN
                          940311 ACTU: 9210.
NEW YORK                  Metropolitan Hospital Center / Pediatrics
                          Department 1901 First Avenue New York, NY
                          10029 Contact: Mavis Dummit (212) 230-7103
                          Contact: message machine (212) 230-6841
                          Contact: beeper (212) 537-1589 OPEN 940815
                          ACTU: 5003.
NEW YORK                  Incarnation Children's Ctr / c/o Columbia
                          Presb Med Ctr 142 Audubon Avenue New York, NY
                          10032 Contact: Pam Clark (212) 928-2228 OPEN
                          930830 ACTU: 4103.
NEW YORK                  The Columbia Presbyterian Medical Hosp
                          (Pediatric) 622 West 168th St Room 1161 New
                          York, NY 10032-3796 Contact: Kathy A Shea
                          (212) 305-7222 OPEN 930830 ACTU: 4101.
NEW YORK                  Harlem Hospital 506 Lenox Avenue New York, NY
                          10037 Contact: Rick Urbano (212) 939-4040
                          Contact: (212) 939-4045 OPEN 931215 ACTU:
                          5006.
NEW YORK                  Lincoln Hospital Center / Department of
                          Pediatrics 234 East 149th Street Bronx, NY
                          10451 Contact: Annie Villareal (718) 579-5329
                          Contact: (718) 579-5000 OPEN 940711 ACTU:
                          5004.
NEW YORK                  Bronx Lebanon Hospital Center / Department of
                          Pediatrics 1650 Selwyn Avenue Room 2C Bronx,
                          NY 10457 Contact: Patrice Edwards-Cihak (718)
                          960-1015 OPEN 931022 ACTU: 6901.
NEW YORK                  Montefiore Medical Center / Adolescent AIDS
                          Program 111 East 210th Street / NW674 Bronx,
                          NY 10467 Contact: Dina Monte (718) 882-0023
                          OPEN 930922 ACTU: 4903.
NEW YORK                  North Shore University Hospital / Pediatric
                          Immunology 350 Community Drive Manhasset, NY
                          11030 Contact: Cathy Macco (516) 773-7676
                          OPEN 930729 ACTU: 5010.
NEW YORK                  Schneider Children's Hospital / Long Island
                          Jewish Med Ctr 270-05 76th Avenue Room 235 /
                          Div of Allergy and Immunology New Hyde Park,
                          NY 11042 Contact: Debby Hickey (718) 470-3300
                          OPEN 930824 ACTU: 5001.
NEW YORK                  King's County Hospital Center / SUNY HSCB 450
                          Clarkson Avenue Brooklyn, NY 11203 Contact:
                          Helen Bergin (718) 245-3342 Contact: (718)
                          245-3341 Contact: (718) 245-4485 OPEN 940214
                          ACTU: 5035.
NEW YORK                  SUNY at Brooklyn / Health Science Center /
                          Pediatrics 450 Clarkson Avenue / Box 24
                          Brooklyn, NY 11203 Contact: Barbara Driscoll
                          (718) 270-3081 OPEN 930402 ACTU: 5008.
NEW YORK                  SUNY Health Science Center at Stony Brook HSC
                          T 15 080 Stony Brook, NY 11794-8111 Contact:
                          Peggy Melendez (516) 444-1313 Contact: (516)
                          444-7692 Contact: beeper (516) 282-8808
                          Contact: Jeannie Conner (516) 444-2724 OPEN
                          931013 ACTU: 5040.
NEW YORK                  Children's Hospital at Albany Medical Center
                          22 New Scotland Avenue Albany, NY 12208
                          Contact: Mary Ellen Adams (518) 432-1501 OPEN
                          930601 ACTU: 5042.
NEW YORK                  SUNY Health Science Center at Syracuse 750
                          East Adams Street Syracuse, NY 13210 Contact:
                          Kathie Shea-Contello (315) 464-6331 OPEN
                          940405 ACTU: 5039.
NEW YORK                  Children's Hospital 219 Bryant Street
                          Buffalo, NY 14222 Contact: Cynthia Kelly
                          (716) 878-7908 OPEN 940303 ACTU: 1104.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 930525 ACTU: 1101.
OHIO                      Children's Hospital 700 Children's Drive
                          Columbus, OH 43205-2696 Contact: Jane Hunkler
                          (614) 722-4460 Contact: (614) 722-6050 OPEN
                          930602 ACTU: 2302.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940610 ACTU: 2501.
OHIO                      Childrens Hospital of Cincinnati Eden and
                          Bethesda Avenue Cincinnati, OH 45267-0405
                          Contact: Jill Leonard (513) 558-6977 OPEN
                          931028 ACTU: 2404.
OTHER                     Ramon Ruiz Arnau University Hospital Laurel
                          Avenue Bayamon, PR 00619 Contact: Leticia
                          Diaz (809) 798-2733 OPEN 930402 ACTU: 5033.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 930611 ACTU: 5031.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          930514 ACTU: 6601.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 931206 ACTU: 6701.
PENNSYLVANIA              Saint Christopher's Hospital for Children /
                          Sect Imm & Rheum Erie Avenue at Front Street
                          Philadelphia, PA 19134-1095 Contact: Carole
                          Treston (215) 427-5284 Contact: FAX (215)
                          427-5555 OPEN 931216 ACTU: 6704.
SOUTH CAROLINA            Medical University of South Carolina Clinical
                          Science Building / 171 Ashley Avenue
                          Charleston, SC 29425-3312 Contact: Genny
                          Connelly (803) 792-2385 OPEN 930520 ACTU:
                          5037.
 
46
UNIQUE IDENTIFIER         NIH/00485
PROTOCOL ID NUMBERS       NIAID ACTG 216
PROTOCOL TITLE            Chemoprevention of Anal Neoplasia Arising
                          Secondary to Anogenital Human Papillomavirus
                          Infection in Persons With HIV Infection.
VERSION NUMBER & DATE     3 (940401)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: PRIMARY: In Phase I, to define a
                          broadly tolerable dose of isotretinoin that
                          can be used in combination with interferon
                          alfa-2a (IFN alfa-2a). In Phase II, to
                          determine trends in efficacy of isotretinoin
                          alone or in combination with IFN alfa-2a as
                          chemoprevention (preventing progression or
                          recurrence) of anal intraepithelial neoplasia
                          in patients with HIV infection. SECONDARY: To
                          evaluate the effects of isotretinoin alone or
                          in combination with IFN alfa-2a on immune
                          function markers, human papillomavirus (HPV)
                          type, and HPV DNA levels.
GENERAL DESCRIPTION       RATIONALE: Patients with HIV infection have a
                          significant risk of recurrence following
                          local ablation of intraepithelial neoplasia;
                          thus, anogenital epithelial may become an
                          increasingly important cause of morbidity,
                          and possibly mortality, as the HIV epidemic
                          matures. Clinical studies of non-HIV-infected
                          subjects have established that synthetic
                          retinoids inhibit the progression of
                          epithelial preneoplastic conditions and some
                          neoplastic states.
GENERAL DESCRIPTION       METHODOLOGY: In the Phase I portion of the
                          study, 10 patients per site each receive
                          isotretinoin in escalating doses, beginning
                          with 0.25 mg/kg daily for weeks 1 and 2,
                          followed by increases to 0.50 mg/kg for weeks
                          3 and 4 and 0.75 mg/kg for weeks 5 and 6. If
                          a patient experiences grade 2 or worse
                          toxicity, dose is reduced to the previously
                          tolerated dose for the remainder of the 6
                          week period. Patients are then reassessed for
                          anal neoplasia; those with no progression and
                          no grade 2 or worse toxicity receive an
                          additional 6 weeks of isotretinoin in
                          combination with 1.5 MU interferon alfa-2a,
                          thrice weekly. For Phase II of the study, a
                          separate group of patients who have undergone
                          ablative therapy are randomized to one of
                          three arms (26 patients/arm): isotretinoin
                          alone at the dose tolerated by at least 60
                          percent of patients in Phase I; isotretinoin
                          plus 1.5 MU interferon alfa-2a; or
                          observation only. Treatment continues for 48
                          weeks.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Anal intraepithelial neoplasia.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA and
                          Western blot. 2. NO active opportunistic
                          infection requiring treatment with prohibited
                          drugs. 3. Current grade 1 anal
                          intraepithelial neoplasia with histologic
                          confirmation (for Phase I patients) OR prior
                          histologically confirmed grade 2 or 3 anal
                          intraepithelial neoplasia, with ablative
                          therapy within the past 30-90 days (for Phase
                          II patients).
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 41,357
STUDY DESIGN              Drug Combination; Dose Escalating; Drug
                          Tolerance; Randomized; 3-Arm
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy, Drug efficacy, Drug tolerance,
                          Secondary prophylaxis, Maximum tolerated dose
                          (MTD).
PROTOCOL DETAILS          PROJECTED ACCRUAL: 182 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 6/182 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. NO active
                          opportunistic infection requiring treatment
                          with prohibited drugs. 3. Current grade 1
                          anal intraepithelial neoplasia with
                          histologic confirmation (for Phase I
                          patients) OR prior histologically confirmed
                          grade 2 or 3 anal intraepithelial neoplasia,
                          with ablative therapy within the past 30-90
                          days (for Phase II patients). 4. Capability
                          of complying with study protocol. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10.0 g/dl. (Transfusion not
                          permitted within 2 weeks prior to study
                          entry).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min. (If
                          creatinine value not available).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 1500 cells/mm3.
                          Alkaline phosphatase <= 2.5 mg/dl. Serum
                          triglyceride < 400 mg/dl.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or two
                          effective methods of birth control /
                          contraception during the study and for 90
                          days after.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. PCP
                          prophylaxis (required for patients with CD4
                          count < 200 cells/mm3). 2. Chemoprophylaxis
                          for candidiasis and herpes simplex. 3.
                          Metronidazole for up to 14 days. 4.
                          Erythropoietin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of ventricular arrhythmias or
                          myocardial infarction. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 90 days after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse or
                          illegal drug use (alcohol consumption is
                          strongly discouraged).
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 20 days
                          prior to study entry: Radiation therapy.
                          Excluded within 14 days prior to study entry:
                          Transfusion.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 20 days
                          prior to study entry: 1. G-CSF. 2.
                          Myelosuppressive antibiotics. 3.
                          Corticosteroids. 4. Biologic response
                          modifiers. 5. Cytotoxic chemotherapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. G-CSF. 2.
                          Myelosuppressive antibiotics. 3.
                          Corticosteroids. 4. Biologic response
                          modifiers. 5. Cytotoxic chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active medical problems for which the patient
                          is undergoing evaluations or for which
                          prohibited therapy is required. 2. Other
                          active malignancies requiring systemic
                          therapy. NOTE: Patients with malignancies
                          being managed with local therapy (e.g.,
                          Kaposi's sarcoma, basal cell carcinoma) may
                          enroll at the discretion of the site
                          investigator. 3. Significant symptomatic
                          cardiac disease.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0034  Interferon Alfa-2a
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0213  Isotretinoin
TRADE NAME OF SUBSTANCE   Drug 1 Roferon-A
MANUFACTURERS             Drug 1: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
MANUFACTURERS             Drug 2: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Phase II: 1.5 MU
                          administered MWF for 48 weeks. Drug 2: Phase
                          I: 0.25, 0.50, and 0.75 mg/kg administered
                          during1-2, 3-4, and 5-6, respectively. Phase
                          II: Best tolerated dose as determined in
                          Phase I, adminisMWF for 48 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 2: Phase I: 0.25, 0.50,
                          and 0.75 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous, 18 MU
                          vials. Drug 2: Oral, 20 and 40 mg capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: Phase I: 12 weeks. Phase
                          II: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Phase I: Dose-limiting toxicity.
                          Phase II: Recurrence of grade 2 or 3 anal
                          intraepithelial neoplasia or progression to
                          invasive cancer; unacceptable toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Attainment of
                          study endpoint. 2. Development of major
                          opportunistic infection. 3. Intercurrent
                          illness that would affect assessment of
                          clinical status or require discontinuation of
                          study drugs. 4. Unacceptable toxicity. 5.
                          Progressive Kaposi's sarcoma that requires
                          systemic chemotherapy. 6. Development of
                          other malignancies requiring radiation or
                          systemic therapy. 7. Pregnancy. 8. Patient
                          noncompliance or desire to withdraw from
                          study.
OTHER TREATMENT INFO.     MODIFICATION: Phase II: For grade 3 toxicity,
                          hold study drug until toxicity resolves to
                          grade 1 or better, then restart at same dose.
                          For grade 3 toxicity that does not resolve
                          within 21 days or that recurs, or for any
                          occurrence of grade 4 toxicity, discontinue
                          drug permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Hoffmann-La Roche,
                          Incorporated.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Anus Neoplasms/ETIOLOGY/*PREVENTION & CONTROL
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Interferon Alfa-2a/*THERAPEUTIC USE
MESH HEADING              Isotretinoin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Papillomavirus, Human
MESH HEADING              Papovaviridae Infections/COMPLICATIONS
MESH HEADING              Tumor Virus Infections/COMPLICATIONS
CAS REGISTRY NUMBER       4759-48-2 (Isotretinoin)
CAS REGISTRY NUMBER       76543-88-9 (Interferon Alfa-2a)
LAST REVISION DATE        941207
ENTRY MONTH               9408
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          940706 ACTU: 0802.
 
47
UNIQUE IDENTIFIER         NIH/00484
PROTOCOL ID NUMBERS       NIAID ACTG 215
PROTOCOL TITLE            A Phase I Study of TNP-470 in the Treatment
                          of AIDS-Associated Kaposi's Sarcoma.
VERSION NUMBER & DATE     5 (940819)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Gill PS
PROTOCOL CHAIRS           CO-CHAIR  Dezube B
GENERAL DESCRIPTION       PURPOSE: To assess toxicity and determine the
                          MTD of intravenous TNP-470 administered
                          weekly in patients with AIDS-related Kaposi's
                          sarcoma. To assess pharmacokinetics and tumor
                          response of the drug.
GENERAL DESCRIPTION       RATIONALE: Since evidence shows that
                          neovascularization is important in the
                          development of Kaposi's sarcoma, drugs that
                          inhibit angiogenesis, such as TNP-470, may be
                          of benefit in patients with the disease.
GENERAL DESCRIPTION       METHODOLOGY: Patients are entered at 4
                          escalating dose levels of TNP-470, ranging
                          from 20-50 mg/m2. Four patients treated at a
                          given dose level must receive at least 4
                          weeks of therapy before escalation in
                          subsequent cohorts proceeds. If 50 percent of
                          patients at a given dose level experience
                          dose-limiting toxicity, the previous dose is
                          defined as the MTD and an additional two
                          patients are treated at the MTD. Patients
                          receive treatment for 12 weeks, followed by 2
                          weeks of rest, followed by an additional 12
                          weeks of treatment. Patients are followed for
                          12 weeks post-treatment.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot. 2. Biopsy-proven
                          cutaneous Kaposi's sarcoma (KS) with 5 or
                          more measurable lesions and no evidence of
                          visceral disease. Pulmonary or symptomatic
                          gastrointestinal KS or acutely
                          life-threatening KS potentially responsive to
                          other therapy is not permitted.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 41,244
STUDY DESIGN              Pharmacokinetic; Dose Escalating; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Maximum tolerated
                          dose (MTD), Pharmacokinetics, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 - 36 patients. (Up to 8
                          patients at each of 4 dose levels)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 36 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 20/20 - 36 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 10 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Cutaneous Kaposi's
                          sarcoma. 3. Life expectancy of at least 3
                          months. 4. Consent of parent or guardian if
                          under 18 years of age. NOTE: This protocol is
                          considered suitable for prison populations.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.0 g/dl. (No transfusion
                          during the week prior to study entry).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: > 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 1000 cells/mm3.
                          PTT or PT < 120 percent of control.
PATIENT AGE               AGE: 12 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study and for 60
                          days after.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. AZT, ddI,
                          ddC, or d4T provided patients have received
                          at least 2 weeks of this therapy prior to
                          study entry. (Combination ddI/ddC is not
                          permitted.) 2. MAI prophylaxis. Required in
                          patients with CD4 count < 200 cells/mm3:
                          Aerosolized pentamidine,
                          trimethoprim/sulfamethoxazole, or dapsone as
                          PCP prophylaxis.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of substanial non-iatrogenic bleeding
                          disorders. 2. History of tumor or
                          malignancies other than Kaposi's sarcoma,
                          with the exception of completely resected
                          basal cell skin carcinoma or in situ cervical
                          carcinoma. 3. History of seizures within the
                          past 10 years. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 11 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control
                          during study and for 60 days after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Unwilling to refrain from
                          unprotected sexual contact or other
                          activities that may result in HIV
                          re-infection.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: 1. Steroids. 2.
                          Antineoplastic drugs. 3. Interferons. 4.
                          Systemic or topical anti-Kaposi's sarcoma
                          agents or regimens. Excluded within 6 weeks
                          prior to study entry: suramin.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Combination therapy with ddI/ddC (although
                          these drugs may be administered alone or in
                          combination with AZT). 2. Anticonvulsive
                          medication. 3. Steroids. 4. Antineoplastic
                          drugs. 5. Interferons. 6. Systemic or topical
                          anti-Kaposi's sarcoma agents or regimens. 7.
                          Suramin. 8. Aspirin. 9. Warfarin. 10.
                          Heparin. 11. Nonsteroidal anti-inflammatory
                          drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Peripheral neuropathy (grade 2 or worse). 2.
                          Underlying severe or life-threatening
                          infection with bacterial, viral, fungal, or
                          protozoal pathogens. 3. Known
                          hypersensitivity to TNP-470, fumagillin, or
                          known related compounds.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0148  TNP-470
MANUFACTURERS             Drug 1: TAKEDA AMERICA Incorporated 101
                          Carnegie Center Princeton, NJ 08540 Contact:
                          Dr Mikihiko Obayashi (609) 452-1113.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 20 - 50 mg/m2 weekly
                          for a minimum of 4 and maximum of weeks, with
                          a 2-week rest after the first 12 weeks
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, 30 mg
                          vials
OTHER TREATMENT INFO.     TREATMENT DURATION: 4-24 weeks.
OTHER TREATMENT INFO.     END POINT: Toxicity, disease progression,
                          development of opportunisitic infection,
                          response.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity, including recurrent grade 3 or 4
                          toxicity. 2. Development of major
                          opportunistic infection that does not resolve
                          within 6 weeks. 3. Intercurrent illness that
                          would affect assessment of clinical status
                          significantly or preclude use of TNP-470. 4.
                          Progressive Kaposi's sarcoma. 5. Other
                          malignancies that require radiation or
                          systemic therapy. 6. Pregnancy.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 toxicity: Hold
                          study drug until toxicity resolves to
                          baseline, then resume at next lower dose
                          level (or 50 percent of dose for first
                          cohort). For grade 1 hematuria, grade 2
                          hemorrhage, or grade 2 or worse coagulation
                          abnormalities: Hold study drug until complete
                          resolution of symptoms, then resume.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents/*ADVERSE EFFECTS/
                          PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antineoplastic Agents)
LAST REVISION DATE        941207
ENTRY MONTH               9305
CALIFORNIA                Kenneth Norris Cancer Hospital / LAC-USC 2020
                          Zonal Avenue Room 309 Los Angeles, CA 90033
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          930611 ACTU: 1203.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          930611 ACTU: 1201.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 930520 ACTU: 2701.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02115 Contact: Sheila Hussey (617)
                          735-4103 OPEN 930514 ACTU: 0102.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 OPEN 940930 ACTU: 0104.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 930915 ACTU:
                          2101.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 940721 ACTU:
                          1802.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940923 ACTU: 1801.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 940627 ACTU: 7401.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 940713 ACTU: 1103.
 
48
UNIQUE IDENTIFIER         NIH/00476
PROTOCOL ID NUMBERS       NIAID ACTG 211
PROTOCOL TITLE            Phase I/II Study of Recombinant Human
                          Interferon-gamma (rIFN-gamma) in HIV-Infected
                          Children.
VERSION NUMBER & DATE     2 (930219)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
PROTOCOL CHAIRS           CHAIR  Shearer WT
PROTOCOL CHAIRS           CO-CHAIR  Abramson SL, Kline MW
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To determine the safety and
                          toxicity of recombinant interferon gamma-1b
                          (rIFN-gamma) in HIV-infected children
                          receiving ongoing zidovudine (AZT) therapy.
                          To document HIV-associated defects in
                          neutrophil and/or monocyte function that are
                          improved with rIFN-gamma. SECONDARY: To
                          determine whether a change in CD4 cell count
                          occurs and to assess virologic status and
                          effects on AZT pharmacokinetics.
GENERAL DESCRIPTION       RATIONALE: It is likely that infants and
                          children severely immunocompromised by HIV
                          infection would respond to immunomodulators
                          that augment different portions of the host
                          defense system. Interferon-gamma has been
                          shown to benefit children with severely
                          compromised nonspecific immunity and may thus
                          be of benefit to those with HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients are treated with
                          subcutaneous rIFN-gamma 3 times a week for 24
                          weeks and are then followed for an additional
                          12 weeks.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Class P-2 symptomatic HIV
                          infection demonstrated as follows: o Children
                          >= 15 months must have EITHER two positive
                          HIV antibody tests by ELISA, with one test
                          confirmed by Western blot OR a positive viral
                          culture (blood or CSF). o Children < 15
                          months of age whose only laboratory evidence
                          of HIV infection is a positive antibody test
                          must also have a positive viral culture
                          (blood or CSF). 2. Ongoing AZT therapy of 6
                          months or longer duration.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND BB4827
STUDY DESIGN              Dose Escalating; Open Label; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug toxicity,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 36 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 11/30 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Class P-2 symptomatic HIV infection.
                          2. Ongoing AZT therapy of 6 months or longer
                          duration. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: > 27 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.6 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: BUN <= 40 mg/dl. White blood cell
                          count > 1500 cells/mm3. Neutrophils > 750
                          cells/mm3.
PATIENT AGE               AGE: 01 Years - 17 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: 1. Ongoing AZT
                          therapy of 6 weeks or longer duration. 2.
                          Ongoing PCP prophylaxis for more than 6 weeks
                          duration.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: 1. AZT
                          therapy. 2. PCP prophylaxis. Allowed: 1.
                          Antipyretics. 2. Antiemetics. 3.
                          Antihistamines. 4. Decongestants. 5. Skin
                          creams and lotions. 6. Immunizations
                          according to current recommendations.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of congestive heart failure or
                          arrhythmias. 2. History of congenital heart
                          disease. 3. History of seizure disorder
                          requiring anticonvulsant medication. (NOTE:
                          History of uncomplicated febrile seizures
                          does not exclude.) [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 11 Months. 18 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Ongoing alcohol or drug use.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Red blood cell
                          transfusion within 4 weeks prior to study
                          entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 8 weeks
                          prior to study entry: Other immunomodulators
                          or IVIG.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral therapy other than AZT. 2.
                          Chemotherapy for active malignancy. 3.
                          Amphotericin B for systemic fungal
                          infections.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Co-enrollment and treatment on
                          other ACTG pediatric studies.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0020  Interferon-gamma
MANUFACTURERS             Drug 1: Genentech Incorporated 460 Point San
                          Bruno Boulevard South San Francisco, CA 94080
                          Contact: Professional Services (800)
                          821-8590.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 50 mcg/m2 3 times a
                          week (MWF) during weeks 1 through 1then 100
                          mcg/m2 3 times a week (MWF) during weeks 13
                          through 2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous, 100 mcg
                          (3 MU) vials
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Primary: Toxicity, improvement in
                          neutrophil and/or monocyte function.
                          Secondary: Change in CD4 cell counts,
                          virologic parameters, effects of study drug
                          on AZT pharmacokinetics.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Grade 4 local
                          or systemic reactions to study therapy or
                          persistent or recurrent grade 3 toxicity at
                          50 percent dose. 2. Sustained increases in
                          viral burden. 3. Patient noncompliance or at
                          the request of the patient, parents or
                          guardian, investigator, FDA, pharmaceutical
                          company, or IND sponsor.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 toxicity: hold
                          drug. If toxicity resolves to grade 2 or
                          better within 14 days, resume drug at 50
                          percent dose. If toxicity persists after 14
                          days, discontinue drug permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Genentech Incorporated.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Interferon-gamma, Recombinant/*ADVERSE
                          EFFECTS/PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Male
CAS REGISTRY NUMBER       0 (Interferon-gamma, Recombinant)
LAST REVISION DATE        941207
ENTRY MONTH               9306
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 940531 ACTU: 6701.
 
49
UNIQUE IDENTIFIER         NIH/00434
PROTOCOL ID NUMBERS       NIAID ACTG 206
PROTOCOL TITLE            A Randomized Phase II Trial to Determine the
                          Safety, Tolerance, and Efficacy of Two Doses
                          of Interferon Alfa-2b Combined With
                          Didanosine in Patients With Kaposi's Sarcoma.
VERSION NUMBER & DATE     3 (930318)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Krown SE
GENERAL DESCRIPTION       PURPOSE: Primary: To evaluate the safety,
                          toxicity, and antitumor activity of two doses
                          of interferon alfa-2b (IFN-alpha) combined
                          with a fixed dose of didanosine (ddI) in
                          patients with Kaposi's sarcoma associated
                          with HIV infection. Secondary: To evaluate
                          the effects of combined IFN-alpha and ddI
                          treatment on HIV expression and markers of
                          immune function.
GENERAL DESCRIPTION       RATIONALE: Previous studies have shown that
                          IFN-alpha can induce regression of Kaposi's
                          sarcoma and suppression of HIV in some
                          patients. Although various trials using
                          IFN-alpha in combination with the nucleoside
                          analog zidovudine have demonstrated a high
                          degree of antitumor activity and evidence of
                          HIV suppression, the overlapping toxicity
                          (primarily neutropenia) of these two agents
                          has proven dose-limiting. The toxicity
                          profile of ddI suggests that this drug may be
                          better tolerated than zidovudine when
                          combined with IFN-alpha.
GENERAL DESCRIPTION       METHODOLOGY: Up to 90 patients are randomized
                          to receive either low or high doses of
                          IFN-alpha (1 or 10 million Units/day) in
                          combination with a fixed dose of ddI.
                          Fourteen patients are initially entered at
                          each dose level. If no objective antitumor
                          responses are observed among the first 14
                          patients at a given dose, no further patients
                          are entered on that treatment arm. If one or
                          more antitumor responses are seen at a given
                          dose, up to 45 patients may be entered on
                          that treatment arm. Patients must complete at
                          least 4 weeks of study therapy to be
                          considered evaluable for tumor response.
                          Treatment is continued until tumor
                          progression or unacceptable toxicity occurs.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Positive antibody to HIV
                          confirmed by any federally licensed ELISA
                          test kit and Western blot. 2. Biopsy-proven
                          Kaposi's sarcoma (at least 5 measurable
                          lesions, with at least 1 measurable cutaneous
                          lesion) involving the skin, lymph nodes, oral
                          cavity, or asymptomatic lesions of the GI
                          tract not requiring systemic chemotherapy.
                          Lung involvement with Kaposi's sarcoma
                          excludes. 3. CD4 count = or > 100 cells/mm3
                          on one occasion within 30 days prior to study
                          entry.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 34,595
STUDY DESIGN              Drug Combination; Multicenter; Open Label;
                          Randomized; Unblinded
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 90 patients. 45 patients
                          per regimen)
PROTOCOL DETAILS          ACTUAL ACCRUAL: 42/90 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 22 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Positive antibody to HIV confirmed
                          by any federally licensed ELISA test kit and
                          Western blot. 2. Biopsy-proven Kaposi's
                          sarcoma (at least 5 measurable lesions, with
                          at least 1 measurable cutaneous lesion)
                          involving the skin, lymph nodes, oral cavity,
                          or asymptomatic lesions of the GI tract not
                          requiring systemic chemotherapy. Lung
                          involvement with Kaposi's sarcoma excludes.
                          3. CD4 count = or > 100 cells/mm3 on one
                          occasion within 30 days prior to study entry.
                          4. Consent of parent or guardian if less than
                          18 years of age. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl. (in the absence of
                          transfusion in the preceding 2 weeks.)
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3. ( 100
                          - 200 - 300 - 400 - 500 - 600 - 700 - 800
                          plus).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Neutrophil count >= 1000 cells/mm3.
                          Serum amylase < 1.5 x ULN. Serum triglyceride
                          <= 400 mg/dl. PT <= 1.3 x control.
PATIENT AGE               AGE: 12 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Negative pregnancy test
                          within 14 days of study entry. Abstinence or
                          agree to use barrier methods of birth control
                          / contraception during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for candidiasis and herpes
                          simplex. 2. Up to 14 days of metronidazole.
                          3. Recombinant erythropoietin. 4. G-CSF (for
                          severe cases of neutropenia). 5. Isoniazid
                          for treatment of TB if given in conjunction
                          with pyridoxine. Required in patients with
                          CD4 counts < 200 cells/mm3: Prophylaxis for
                          PCP.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Opportunistic infection or B symptoms. 2.
                          Prior grade 3 or 4 toxicity attributed to ddI
                          therapy. 3. Prior history of peripheral
                          neuropathy (= or > grade 1), pancreatitis,
                          intractable diarrhea, or active seizure
                          disorder not well controlled by anti-seizure
                          medications. 4. History of myocardial
                          infarction or ventricular arrhythmias. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 11 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. Positive pregnancy test
                          within 14 days of study entry. No abstinence
                          or no agreement to use barrier methods of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Alcohol consumption is
                          strongly discouraged. Patients considered to
                          be noncompliant should be excluded.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          within 30 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          IFN-alpha. 2. Corticosteroids, biological
                          response modifiers, cytotoxic chemotherapy,
                          or known neurotoxic drugs (other than ddI or
                          ddC) within 30 days prior to study entry. 3.
                          Therapy with antiretroviral drugs (other than
                          ddI) within 7 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          investigational, antiviral, immunomodulating,
                          or antitumor agents. 2. Drugs associated with
                          peripheral neuropathy (other than ddI).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Concurrent opportunistic infection or B
                          symptoms. 2. Visceral (non-nodal) Kaposi's
                          sarcoma requiring cytotoxic chemotherapy. 3.
                          Severe (> 2+) tumor-associated edema. 4.
                          Concurrent neoplasia other than basal cell
                          carcinoma, or anogenital intraepithelial
                          neoplasia. 5. Current clinical evidence of
                          peripheral neuropathy (= or > grade 1),
                          pancreatitis, intractable diarrhea, or active
                          seizure disorder not well controlled by
                          anti-seizure medications. 6. Significant
                          symptomatic cardiac disease. 7. Medical
                          contraindication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0035  Interferon Alfa-2b
MANUFACTURERS             Drug 1: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
MANUFACTURERS             Drug 2: Schering-Plough Corporation 2000
                          Galloping Hill Road Kenilworth, NJ 07033
                          Contact: Dr Janice Albrecht (908) 298-7985.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or 100 mg in
                          patients weighing < 50 kg) q 12 hrDrug 2: 1
                          or 10 million U daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 400 mg (or 200 mg in
                          patients weighing < 50 kg). Drug 2: 1 or 10
                          million U
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral; 25, 50, and 100
                          mg chewable, dispersible tablets.Drug 2:
                          Subcutaneous, 10 million unit vials
OTHER TREATMENT INFO.     TREATMENT DURATION: Until tumor progression
                          or unacceptable toxicity occurs.
OTHER TREATMENT INFO.     END POINT: Tumor response, dose-limiting
                          toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Development of
                          tumor progression, new visceral involvement,
                          or new or increasing tumor-related edema. 2.
                          Unacceptable toxicity. 3. Major opportunistic
                          infection. 4. Other malignancies requiring
                          radiation or systemic therapy. 5.
                          Intercurrent illness that would affect
                          assessments of clinical status to a
                          significant degree or require discontinuation
                          of drugs. 6. Pregnancy. 7. Patient
                          noncompliance.
OTHER TREATMENT INFO.     MODIFICATION: For grade 2 peripheral
                          neuropathy: hold ddI until return to grade 1
                          or better, then resume ddI at reduced dose.
                          For a second occurrence of grade 2 or any
                          occurrence of grade 3 peripheral neuropathy,
                          discontinue study medication permanently. In
                          general, for a first occurrence of grade 2
                          cardiac (excluding hemorrhage), stomatitis,
                          renal, bladder, pulmonary, allergic (other
                          than rash), or mucocutaneous toxicity, or a
                          first occurrence of other grade 3 toxicities:
                          hold study medication until toxicity returns
                          to acceptable level, then resume IFN-alpha at
                          50 percent dose and ddI at either a reduced
                          or full dose (depending on the specific
                          toxicity). If these toxicities recur, study
                          medication is permanently discontinued. Study
                          medication is also discontinued for a first
                          occurrence of grade 3 or higher cardiac
                          (including hemorrhage), stomatitis, renal,
                          bladder, pulmonary, allergic, or
                          mucocutaneous toxicity or any grade 4
                          hematologic (including anemia), headache,
                          constipation, or hepatic toxicity or grade 4
                          nausea or vomiting.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Bristol-Myers Squibb
                          Company, Schering-Plough Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS/DRUG THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Didanosine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Interactions
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Interferon-alpha/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Interferon-alpha)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        941207
ENTRY MONTH               9208
CALIFORNIA                Kaiser Permanente Medical Group / Stanford
                          University 2590 Geary Boulevard San
                          Francisco, CA 94115 Contact: Gretchen Van
                          Raalte (415) 202-3482 OPEN 920804 ACTU: 0502.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 920811 ACTU:
                          6101.
COLORADO                  Denver Department of Health and Hospitals /
                          Univ of CO Colorado ACTU / Campus Box B 163 /
                          4200 East Ninth Avenue Denver, CO 80262
                          Contact: M Graham Ray (303) 270-8551 OPEN
                          930325 ACTU: 6102.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941005 ACTU:
                          6104.
COLORADO                  Kaiser Permanente Franklin Med Cntr / Univ
                          Col Hlth Sci Cntr 4200 East Ninth Avenue /
                          Colorado ACTU / Campus Box B-163 Denver, CO
                          80262 Contact: Graham Ray (303) 270-8551
                          Contact: FAX (303) 270-6102 OPEN 930624 ACTU:
                          6103.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 921001 ACTU: 2701.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940902 ACTU: 2702.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940502 ACTU: 2601.
MASSACHUSETTS             Bay State Medical Center 759 Chestnut Street
                          Springfield, MA 01199 Contact: Deborah
                          Naglieri-Prescod (413) 784-3046 OPEN 921007
                          ACTU: 3002.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 OPEN 930512 ACTU: 0104.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 920818 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 920818
                          ACTU: 2102.
NEW YORK                  Memorial Hospital / Memorial Sloan-Kettering
                          Cancer Center 1275 York Avenue New York, NY
                          10021 Contact: Gloria Gilbert (212) 639-7169
                          OPEN 920729 ACTU: 2202.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          930630 ACTU: 1801.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 940317 ACTU: 7502.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930818 ACTU: 7403.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930818 ACTU: 7402.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 930818 ACTU: 7401.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          930610 ACTU: 1102.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 941102 ACTU:
                          2401.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 930316
                          ACTU: 5401.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 930518 ACTU: 6201.
 
50
UNIQUE IDENTIFIER         NIH/00482
PROTOCOL ID NUMBERS       NIAID ACTG 203P
PROTOCOL TITLE            A Phase I Pilot Study of the Safety and
                          Efficacy of Interferon Alfa-2b (IFN alfa-2b)
                          in Combination With Nucleoside Analogue
                          Therapy in Patients With Combined Hepatitis C
                          (HCV) and Advanced Human Immunodeficiency
                          Virus (HIV) Infections.
VERSION NUMBER & DATE     1 (921203)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To investigate the toxicity of
                          interferon alfa-2b (IFN alfa-2b) in
                          combination with nucleoside analogue therapy
                          in HIV-positive patients with chronic
                          hepatitis C. To determine the efficacy of
                          treatment with IFN alfa-2b for chronic
                          hepatitis C in patients with advanced HIV
                          infections treated with nucleoside therapy.
GENERAL DESCRIPTION       RATIONALE: IFN alfa-2b has HIV inhibitory
                          properties and has also been approved for
                          treatment of chronic hepatitis C. Studies
                          have shown that IFN alfa-2b is effective in
                          asymptomatic HIV-positive patients with
                          chronic hepatitis C, but the drug's benefit
                          against hepatitis C in patients with advanced
                          HIV infection has not been determined.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive interferon
                          alfa-2b subcutaneously at a dose of 3 million
                          units 3 times weekly for 6 months. If no
                          response is seen after 18 weeks of therapy or
                          if an initial response is followed by relapse
                          while on therapy, dose is increased to 5
                          million units. Patients who require a dose
                          escalation should continue on IFN alfa-2b for
                          an additional 6 months. All patients will
                          also receive available nucleoside analogue
                          therapy (zidovudine, didanosine,
                          dideoxycytidine) at currently accepted doses
                          as clinically appropriate.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Hepatitis C.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive by ELISA
                          confirmed by Western blot or other
                          confirmatory studies such as a positive HIV
                          culture, positive HIV antigen, or plasma
                          viremia. 2. Hepatitis C virus (HCV) infection
                          documented by positive test for HCV RNA by
                          PCR and HCV antibody by one of the more
                          sensitive ELISA assays. 3. CD4 count <= 200
                          cells/mm3 on at least two determinations.
                          NOTE: At least two patients will have CD4
                          count <= 50 cells/mm3. 4. No severe liver
                          disease (Grade C Childs-Pugh classification)
                          or chronic liver disease not caused by
                          hepatitis C.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND BB4878
STUDY DESIGN              Prospective; Drug Combination; Nonrandomized;
                          Multicenter; Pilot Study
PROTOCOL DETAILS          STUDY INTENT: Drug toxicity, Drug efficacy,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 10 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 6
                          months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 10/10 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV positivity. 2. Documented
                          hepatitis C virus. 3. CD4 count <= 200
                          cells/mm3. 4. No severe liver disease (Grade
                          C Childs-Pugh classification) or chronic
                          liver disease not caused by hepatitis C. 5.
                          Willingness to be followed for the duration
                          of treatment and follow-up period. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 200 cells/mm3. ( 0 -
                          100 - 200 ).
PATIENT INCLUSION CRIT.   SGPT(ALT): >= 1.5 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior AZT, ddI,
                          and ddC.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Treatment
                          or suppression of opportunistic infections
                          with standard drugs. 2. Pneumovax, HIB,
                          tetanus, influenza, and hepatitis B vaccines.
                          3. Clinically indicated antibiotics. 4. Short
                          courses of steroids (< 21 days) for acute
                          problems not related to hepatitis C. 5. Other
                          regularly prescribed medications such as
                          analgesics, nonsteroidal anti-inflammatory
                          agents, antipyretics, allergy medications,
                          and oral contraceptives.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy other than local irradiation to the
                          skin.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prednisone
                          within 12 weeks prior to study entry (if
                          patient has received prior daily doses for 1
                          month or longer duration). 2. Acute therapy
                          for an infection within 2 weeks prior to
                          study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Nonnucleoside analogue therapy for HIV. 2.
                          Biologic response modifiers. 3. Systemic
                          cytotoxic chemotherapy. 4. Chronic systemic
                          steroid use.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Hepatitis B (HBsAg positive). 2. Autoimmune
                          hepatitis (FANA titer >= 1:160 and
                          anti-smooth muscle antibody titer >= 1:160).
                          3. Wilson's disease. 4. alpha-1 antitrypsin
                          deficiency. 5. Hemochromatosis. 6. Malignancy
                          requiring systemic chemotherapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0035  Interferon Alfa-2b
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0015  Dideoxycytidine
TRADE NAME OF SUBSTANCE   Drug 1 Intron-A
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
TRADE NAME OF SUBSTANCE   Drug 3 Videx
TRADE NAME OF SUBSTANCE   Drug 4 Hivid
MANUFACTURERS             Drug 1: Schering-Plough Corporation 2000
                          Galloping Hill Road Kenilworth, NJ 07033
                          Contact: Dr Janice Albrecht (908) 298-7985.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 3: Bristol-Myers Squibb Company 2400
                          West Lloyd Expressway Evansville, IN
                          47721-0001 Contact: DDI Information (800)
                          662-7999.
MANUFACTURERS             Drug 4: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 3 MIU thrice weekly
                          (MWF) for 6 months. Drug 2: Administered at
                          currently accepted doses. Drug 3:
                          Administered at currently accepted doses.
                          Drug 4: Administered at currently accepted
                          doses
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous, 10 MIU
                          vials
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 6 months.
OTHER TREATMENT INFO.     END POINT: Toxicity, normalization of serum
                          ALT, loss of serum hepatitis C virus RNA,
                          survival, progression of liver disease.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Pregnancy. 3. Desire of patient
                          to withdraw from study. 4. Treatment
                          considered life-threatening to patient.
OTHER TREATMENT INFO.     MODIFICATION: For a first, second, or third
                          occurrence of neutrophils < 500 cells/mm3:
                          Hold IFN alfa-2b until count rises above 500,
                          then resume at full dose (first occurrence)
                          or reduced dose (second and third
                          occurrences). For a fourth occurrence of
                          neutrophils < 500 cell/mm3, discontinue study
                          drug permanently. For recurrent grade 3 or 4
                          anemia: Hold IFN alfa-2b until toxicity
                          resolves to grade 1 or better, then resume at
                          50 percent dose. For an additional occurrence
                          within a 30-day period, discontinue study
                          drug permanently. For direct
                          hyperbilirubinemia > 3.5 to 5 x ULN: Hold IFN
                          alfa-2b; if toxicity resolves within 4 weeks,
                          resume study drug at reduced dose, but if
                          toxicity does not resolve within 4 weeks or
                          recurs at the reduced dose, discontinue study
                          drug permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Schering-Plough Corporation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS/DRUG THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Hepatitis C/COMPLICATIONS/ETIOLOGY/*THERAPY
MESH HEADING              Human
MESH HEADING              Interferon Alfa-2b/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Opportunistic Infections/COMPLICATIONS/
                          ETIOLOGY/THERAPY
MESH HEADING              Zalcitabine/*THERAPEUTIC USE
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
CAS REGISTRY NUMBER       99210-65-8 (Interferon Alfa-2b)
LAST REVISION DATE        941207
ENTRY MONTH               9307
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 930702 ACTU: 2601.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 930702 ACTU: 0401.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 940609 ACTU: 7502.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940523
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940523 ACTU: 1901.
PENNSYLVANIA              Milton S Hershey Medical Center / Hemophilia
                          Cntr of W Penn 812 Fifth Avenue Pittsburgh,
                          PA 15219 Contact: Dr Margaret V Ragni (412)
                          622-7270 OPEN 930702 ACTU: 9318.
PENNSYLVANIA              Pennsylvania State University / Hershey
                          Medical Center 500 Univ Drive / PO Box 850 /
                          Biomedical Rsrch Bldg C-6833 Hershey, PA
                          17033 Contact: Francine Damianos (717)
                          531-7488 OPEN 931216.
 
51
UNIQUE IDENTIFIER         NIH/00516
PROTOCOL ID NUMBERS       NIAID ACTG 202
PROTOCOL TITLE            Dexamethasone in Cryptococcal Meningitis.
VERSION NUMBER & DATE     4 (940802)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Jacobson J
GENERAL DESCRIPTION       PURPOSE: To evaluate the effect of
                          corticosteroids on reducing elevated
                          intracranial pressure in cryptococcal
                          meningitis. To evaluate the safety of
                          corticosteroids in patients with cryptococcal
                          meningitis and intracranial hypertension.
GENERAL DESCRIPTION       RATIONALE: In AIDS patients with cryptococcal
                          meningitis, a correlation has been found
                          between early death and elevated intracranial
                          pressure. Since dexamethasone has been found
                          to reduce intracranial pressure resulting
                          from other forms of meningitis, it may be of
                          benefit in AIDS patients with cryptococcal
                          meningitis.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive dexamethasone or placebo every 6
                          hours for 72 hours (days 1 through 3).
                          Additionally, standard antifungal therapy
                          with amphotericin B and flucytosine is given
                          for 2 weeks, followed by fluconazole for 8
                          weeks. Lumbar punctures will be performed
                          daily on days 1 through 3, on days 7 and 14,
                          and at week 10.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Cryptococcal meningitis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented initial episode or
                          relapse of acute cryptococcal meningitis.
                          (NOTE: Patients must be untreated for this
                          episode except for administration of a test
                          dose of 1 g or less amphotericin B.) 2. Acute
                          cryptococcal meningitis with cerebrospinal
                          fluid opening pressure >= 250 mm H2O prior to
                          receipt of antifungal therapy for this
                          episode. 3. HIV infection documented by HIV
                          antibody (by ELISA confirmed by Western
                          blot), serum p24 antigen, or recovery of HIV
                          in culture; OR a diagnosis of AIDS based on a
                          documented AIDS-defining opportunistic
                          infection. NOTE: Patients with a history of
                          high-risk behavior for HIV infection
                          (bisexual or homosexual men, intravenous drug
                          abusers, recipients of blood or blood
                          products prior to May 1985, or sexual
                          partners of any of the above) may enroll
                          pending receipt of HIV documentation.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 41,525
STUDY DESIGN              Multicenter; Placebo-Controlled;
                          Double-Blind; Randomized; Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 36 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 10 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 5/36 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 13 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented initial episode or
                          relapse of acute cryptococcal meningitis.
                          (NOTE: Patients must be untreated for this
                          episode except for administration of a test
                          dose of 1 g or less amphotericin B.) 2. Acute
                          cryptococcal meningitis with cerebrospinal
                          fluid opening pressure >= 250 mm H2O prior to
                          receipt of antifungal therapy for this
                          episode. 3. Documented HIV infection OR a
                          diagnosis of AIDS based on a documented
                          AIDS-defining opportunistic infection. 4.
                          Ability to begin therapy within 8 hours after
                          the pre-entry lumbar puncture. 5. Consent of
                          parent or guardian if less than 18 years of
                          age. NOTE: Comatose patients eligible
                          provided informed consent can be provided by
                          guardian or next of kin. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or agree to use
                          barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Aerosolized pentamidine or systemic
                          chemoprophylaxis for PCP. 2. Preventive
                          therapy for steroid-associated ulcers and any
                          other therapies required to manage steroid
                          toxicity (e.g., insulin).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 7 days
                          prior to study entry: Corticosteroids,
                          mannitol, urea preparations, acetazolamide,
                          or more than 24 hours of phenytoin.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Acetazolamide, mannitol, urea preparations,
                          and other corticosteroids during the first 72
                          hours of the study. 2. Treatment or
                          prophylaxis with other systemic antifungal
                          agents at any time. 3. Antiretroviral therapy
                          during the first 72 hours of the study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Concurrent CNS disease such as another
                          infection or neoplasm that would interfere
                          with assessment of response. 2. Prison
                          incarceration.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0013  Dexamethasone
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0006  Amphotericin B
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0049  Flucytosine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0005  Fluconazole
MANUFACTURERS             Drug 1: Merck and Company Incorporated
                          Professional Services West Point, PA 19486
                          Contact: Professional Information (215)
                          661-7300 Contact: Prof Info / Call Collect
                          (215) 652-3298.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 10 mg (or placebo)
                          loading dose followed by 4 mg (or placebo) q
                          6 hr for 72 hr. Drug 2: 0.7 mg/kg daily for
                          at least 2 weeks. Drug 3: 100 mg/kg daily (in
                          4 divided doses) for at least 2 weeDrug 4:
                          400 mg daily for the first 2 days after
                          completion of amphotericin B/flucytosine,
                          then 200 mg daily for an additionalweeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 16 mg (after loading
                          dose). Drug 2: 0.7 mg/kg. Drug 3: 100 mg/kg.
                          Drug 4: 400 mg (for 2 days), then 200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, 4 mg
                          vials. Drug 2: Intravenous. Drug 3:
                          Intravenous (or if necessary, nasogastric).
                          Drug 4: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: 72 hours for steroid
                          phase of study; 10 weeks for antifungal
                          therapy phase.
OTHER TREATMENT INFO.     END POINT: Primary: Change in opening
                          cerebrospinal fluid pressure at 24 hours;
                          serious adverse events. Secondary: Changes in
                          opening cerebrospinal fluid pressure at 48
                          and 72 hours; survival; neurologic deficits;
                          quantitative cryptococcal culture
                          measurements; cryptococcal antigen titer; CSF
                          leucocyte counts, glucose, and protein
                          levels.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity attributed to study drug. 2.
                          Requirement for treatment with prohibited or
                          restricted medications.
OTHER TREATMENT INFO.     MODIFICATION: Flucytosine is held for grade 4
                          hepatic or hematologic toxicity and resumed
                          at full dose or reduced dose, respectively,
                          when toxicity resolves to grade 3 or better.
                          For a second occurrence of grade 4 hepatic
                          toxicity or for a third occurrence of grade 4
                          hematologic toxicity, flucytosine is
                          discontinued permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Amphotericin B/*THERAPEUTIC USE
MESH HEADING              Brain Diseases/*DRUG THERAPY/ETIOLOGY
MESH HEADING              Cryptococcosis/*DRUG THERAPY/ETIOLOGY
MESH HEADING              Dexamethasone/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Fluconazole/*THERAPEUTIC USE
MESH HEADING              Flucytosine/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Meningitis/*DRUG THERAPY/ETIOLOGY
MESH HEADING              Middle Age
MESH HEADING              Opportunistic Infections/COMPLICATIONS/*DRUG
                          THERAPY
CAS REGISTRY NUMBER       1397-89-3 (Amphotericin B)
CAS REGISTRY NUMBER       2022-85-7 (Flucytosine)
CAS REGISTRY NUMBER       50-02-2 (Dexamethasone)
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        941207
ENTRY MONTH               9306
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 940919 ACTU: 5801.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 931014 ACTU: 5701.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 940408
                          ACTU: 0901.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 931215 ACTU: 2701.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 930813 ACTU:
                          1802.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          930825 ACTU: 1801.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 930621
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 930621 ACTU: 1901.
NEW YORK                  Bronx Veterans Administration Medical Center
                          130 West Kingsbridge Road Bronx, NY 10468
                          Contact: Nancy Ostrow (718) 584-9000 X
                          667Contact: (718) 584-9000 X 667OPEN 930527
                          ACTU: 1804.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 930712
                          ACTU: 5901.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          940706 ACTU: 1102.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 941004
                          ACTU: 2301.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 931201
                          ACTU: 5401.
 
52
UNIQUE IDENTIFIER         NIH/00425
PROTOCOL ID NUMBERS       NIAID ACTG 201
PROTOCOL TITLE            A Phase I, Dose-Escalating Safety and
                          Tolerance Study of sCD4-PE40 in HIV-Infected
                          Persons.
VERSION NUMBER & DATE     7 (940422)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  van der Horst C
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          tolerance of sCD4-PE40 given at various
                          dosing intervals and concentrations. To
                          determine whether frequent dosing alters
                          immunogenicity or toxicity. To obtain
                          preliminary data to ascertain whether
                          sCD4-PE40 has activity against HIV in human
                          subjects. To determine whether there is any
                          additive toxicity with combined use of
                          sCD4-PE40 and zidovudine (AZT).
GENERAL DESCRIPTION       RATIONALE: There is some evidence that AZT
                          and sCD4-PE40, an experimental drug with
                          anti-HIV activity previously demonstrated in
                          vitro, may produce increased benefit when
                          used in combination in HIV-infected patients.
GENERAL DESCRIPTION       METHODOLOGY: Cohorts of six patients each
                          receive escalating doses of 20-640 mcg/m2
                          sCD4-PE40 in a single IV weekly dose for 8
                          weeks. All six patients at a given dose must
                          complete 2 weeks of therapy without
                          dose-limiting toxicity before dose escalation
                          in subsequent patient cohorts may occur. The
                          MTD is defined as the dose of sCD4-PE40
                          immediately below that at which two or more
                          of six patients experience grade 3 or higher
                          toxicity or one or more of six patients
                          experience grade 4 toxicity. After the MTD
                          for the once-weekly schedule is reached,
                          subsequent cohorts receive escalated doses of
                          sCD4-PE40 on a 5x weekly schedule for
                          approximately 4 weeks, in an attempt to
                          establish the MTD for that schedule. When an
                          MTD has been determined for the 5x weekly
                          schedule, and if antiretroviral activity is
                          observed, six additional patients receive
                          this dose combined with AZT (100 mg 5x daily)
                          for 4 weeks.
PROTOCOL PHASE            Phase I B
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented positive antibody
                          to HIV by any federally licensed ELISA test
                          kit, confirmed by another method such as
                          Western blot, RIA, HIV culture, etc. If a
                          prior diagnosis of AIDS has not been
                          established by CDC criteria, a confirmatory
                          test is required. 2. CD4 count = or < 300
                          cells/mm3 within 4 weeks prior to study
                          entry. 3. Must be p24 antigen positive.
                          Patients entering the AZT portion of the
                          study only: Must be AZT naive or have had
                          less than 2 months of AZT therapy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    BB IND 4442
STUDY DESIGN              Prospective; Dose Escalating; Open Label
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug dosing schedule, Maximum tolerated dose
                          (MTD).
PROTOCOL DETAILS          PROJECTED ACCRUAL: 64 patients. 6
                          patients/dose
PROTOCOL DETAILS          ACTUAL ACCRUAL: 64/64 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection by ELISA
                          confirmed by a second method. If a prior
                          diagnosis of AIDS has not been established by
                          CDC criteria, a confirmatory test is
                          required. 2. CD4 count = or < 300 cells/mm3
                          within 4 weeks prior to study entry. 3.
                          Positive p24 antigen. Patients entering the
                          AZT portion of the study only: Must be AZT
                          naive or have had less than 2 months of AZT
                          therapy. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl. (Transfusion
                          permitted.)
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 300 cells/mm3. ( 0 -
                          100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   SGOT(AST): < 1.25 x ULN. (ULN = upper limit
                          of normal.)
PATIENT INCLUSION CRIT.   SGPT(ALT): < 1.25 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: > 60.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 1.25 x ULN.
                          Absolute neutrophil count >= 1000 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 7 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. PCP
                          prophylaxis with aerosolized pentamidine,
                          trimethoprim / sulfamethoxazole, or dapsone.
                          2. Clotrimazole troches or nystatin oral
                          suspension for oral candidiasis. 3. Acyclovir
                          (up to 1000 mg/day for 10 days) for herpes
                          lesions. 4. Erythropoietin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 7 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current active alcoholism or
                          active substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Other
                          antiretroviral or immunomodulator agents
                          (including but not limited to AZT, ddI, ddC,
                          interferon, and steroids) within 4 weeks
                          prior to study entry. 2. Ribavirin within 90
                          days prior to study entry. 3. Cytotoxic
                          chemotherapy within one month prior to study
                          entry. 4. Prior soluble CD4 or CD4-Ig.
                          Excluded in patients entering the AZT portion
                          of the study: more than 2 months of prior AZT
                          therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Hepatotoxic agents. 2. Other antiretroviral
                          or immunomodulator agents (including but not
                          limited to AZT, ddI, ddC, interferon, and
                          steroids). 3. Other investigational drugs. 4.
                          Systemic therapy for malignancy. 5. G-CSF and
                          GM-CSF.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Hemophilia. 2. Acute medical problems
                          (including active opportunistic infections
                          such as active cryptococcosis, Pneumocystis
                          carinii, herpes zoster, histoplasmosis, or
                          CMV or nonopportunistic diseases including
                          liver disease, renal disease, or orthostatic
                          hypotension) at time of study entry. 2.
                          Active pulmonary disease. 3. Chronic active
                          hepatitis B surface antigenemia or unstable
                          hepatitis C. 4. Current diagnosis of
                          malignancy for which systemic therapy would
                          be required during the study. 5. Inadequate
                          intravenous access.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0118  sCD4-PE40 (Recombinant
                          Soluble
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: The Upjohn Company 7000 Portage Road
                          Kalamazoo, MI 49001 Contact: James VanSweden
                          (616) 323-4696.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 mg 5x daily for
                          8 weeks (in selected patients). Drug 2: 20,
                          40, 80, 160, 320, and 640 mcg/m2 weekly
                          administeresingle dose for 8 weeks, or
                          divided into 5 equal doses per
                          weekapproximately 4 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules.
                          Drug 2: Intravenous, 1330 mcg vials
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 or 8 weeks.
OTHER TREATMENT INFO.     END POINT: MTD of sCD4-PE40 administered once
                          a week and five times per week. HIV plasma
                          and lymphocyte culture titers. Concentration
                          of circulating HIV p24 antigen. Amount of HIV
                          DNA by PCR in lymphocytes. CD4 lymphocyte
                          count.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Major,
                          unexpected, or life-threatening toxicity
                          requiring drug discontinuation. 2.
                          Development of intercurrent illness such as
                          opportunistic infection. 3. Generalized
                          debilitation or mental incapacity that would
                          preclude informed consent. 4. Indication for
                          systemic cytotoxic therapy for a newly
                          diagnosed malignancy. 5. Pregnancy. 6.
                          Further participation is deemed detrimental
                          to patient's health or well-being. 7.
                          Administrative reasons such as patient
                          noncompliance or a major protocol violation.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 cutaneous or
                          hematologic toxicity, grade 3 headache,
                          constipation, or diarrhea, grade 4 nausea or
                          vomiting, or grade 2 hemorrhagic, other
                          gastrointestinal, renal, bladder, pulmonary,
                          allergic (except skin rashes), cardiac,
                          neurologic, or other pain-related toxicities:
                          hold study drug until return to pretherapy or
                          grade 1, then resume at 50 percent dose. For
                          persistent grade 3 hepatic toxicity, hold
                          study drug until return to grade 1, then
                          resume at 50 percent dose. Study drug is
                          permanently discontinued for the following:
                          persistent grade 4 hepatic toxicity in
                          patients receiving once-weekly doses or an
                          initial unresolved occurrence of grade 4
                          hepatic toxicity in all other patients; grade
                          4 hematologic toxicity, or grade 3 or 4
                          hemorrhagic, gastrointestinal (except grade 3
                          nausea or vomiting), renal, bladder,
                          pulmonary, febrile, allergic, cutaneous,
                          cardiac, neurologic, or pain-related
                          toxicities. Study drug is also permanently
                          discontinued for recurrent toxicity at a 50
                          percent dose.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), The Upjohn Company /
                          Antiretrovirals, Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antigens, CD4/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Recombinant Proteins/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Zidovudine/*ADVERSE EFFECTS/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Recombinant Proteins)
CAS REGISTRY NUMBER       0 (Antigens, CD4)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        941207
ENTRY MONTH               9206
CALIFORNIA                University of California at Los Angeles
                          School of Medicine 60051 CHS / 10833 Le Conte
                          Avenue Los Angeles, CA 90024-1793 Contact:
                          Susan G McCarthy (310) 825-1301 OPEN 920610
                          ACTU: 0601.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 930427 ACTU: 5701.
LOUISIANA                 Tulane U School of Medicine \ General
                          Clinical Research Ctr 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Dana Wineski
                          (504) 585-4020 OPEN 920807.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 920610 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 920610 ACTU:
                          0202.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          920522 ACTU: 3201.
 
53
UNIQUE IDENTIFIER         NIH/00461
PROTOCOL ID NUMBERS       NIAID ACTG 200
PROTOCOL TITLE            A Phase III Randomized Trial of Topical
                          Vaginal Fluorouracil (5-Fluorouracil, 5-FU)
                          Maintenance Therapy Versus Observation After
                          Standard Treatment for High-Grade Cervical
                          Dysplasia in HIV-Infected Women.
VERSION NUMBER & DATE     2 (941012)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Maiman M
PROTOCOL CHAIRS           CO-CHAIR  Watts DH
GENERAL DESCRIPTION       PURPOSE: To determine the efficacy and safety
                          of intravaginal fluorouracil administered as
                          prophylaxis in HIV-infected women who have
                          received standard ablative therapy (surgery)
                          for high-grade cervical dysplasia (pre-cancer
                          of the cervix; cervical intraepithelial
                          neoplasia). To correlate time to recurrence
                          of cervical dysplasia with T-cell function.
GENERAL DESCRIPTION       RATIONALE: Women with HIV infection are at
                          greater risk for cervical dysplasia. Because
                          of the likelihood that untreated or recurrent
                          cervical dysplasia may progress to invasive
                          cancer, there is an urgent need to develop
                          appropriate therapies.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either intravaginal fluorouracil or
                          no treatment (observation only). Fluorouracil
                          cream is self-administered via applicator at
                          biweekly intervals for 6 months. Patients are
                          evaluated for recurrent cervical dysplasia by
                          cytology and colposcopy with or without
                          biopsy.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Dysplasia, Cervical.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA
                          confirmed by Western blot. 2. History of
                          histologically diagnosed grade II or III
                          cervical intraepithelial neoplasia (CIN) that
                          was successfully treated by laser therapy,
                          cryotherapy, loop excision, or cone biopsy
                          within the past 12 weeks. Mild cervical
                          dysplasia (grade I CIN) is not eligible. 3.
                          History of vaginal intraepithelial neoplasia
                          (VAIN) or vulvar intraepithelial neoplasia
                          (VIN) is permitted. Patients with vaginal or
                          vulvar warts are eligible, but such lesions
                          must be biopsied to prove absence of
                          dysplasia.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 40,765
STUDY DESIGN              Randomized; Open Label; Multicenter; 2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Secondary prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 158 patients. (79 patients
                          per treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 6 months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 38/158 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 26 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Prior cervical
                          dysplasia (grade II or III cervical
                          intraepithelial neoplasia) successfully
                          treated with an ablative procedure within the
                          past 12 weeks. 3. Patients less than 18 years
                          of age must have consent of parent or
                          guardian. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 7 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 30 days after.
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Required: Ablative therapy
                          for cervical dysplasia within the past 8
                          weeks.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretrovirals (AZT, ddI, ddC) and
                          immunomodulators (interferon and
                          interleukin). 2. Prophylaxis or treatment for
                          opportunistic infections. 3. Vaginal
                          antifungal agents or other indicated vaginal
                          medications (although not permitted on day of
                          fluorouracil application). 4. Contraceptives.
                          5. Acyclovir (prophylaxis or treatment) in
                          patients with a history of primary or
                          recurrent genital herpes.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Malignancy requiring cytotoxic chemotherapy
                          within the 3 months prior to study entry. 2.
                          Prior hysterectomy. 3. History of allergic
                          reaction or severe hypersensitivity to
                          fluorouracil. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   SEX: MALE
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 7 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control during
                          study and for 30 days after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Fluorouracil
                          (systemic or topical) within 3 months prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapy for malignancy. 2. High-dose
                          steroids (> 10 mg/day prednisone or its
                          steroid equivalent).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Untreated or persistent vaginal or vulvar
                          dysplasia. 2. Colposcopy or biopsy
                          inconclusive or positive for dysplasia. 3.
                          Active genital ulcerative disease such as
                          syphilitic chancre or herpes ulcer. 4.
                          Adenocarcinoma in situ.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0161  Fluorouracil (Topical)
TRADE NAME OF SUBSTANCE   Drug 1 Efudex
MANUFACTURERS             Drug 1: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 2 g biweekly for 6
                          months
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravaginal, 5% cream
OTHER TREATMENT INFO.     TREATMENT DURATION: 6 months.
OTHER TREATMENT INFO.     END POINT: Time to development of recurrent
                          dysplasia; frequency of recurrence of
                          dysplasia as a function of CD4 and CD8
                          counts; dose-limiting toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Recurrence of
                          cervical dysplasia. 2. Pregnancy. 3. Third
                          occurrence of grade 3 or 4 toxicity.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 or 4 toxicity: hold
                          fluorouracil until 4 weeks after toxicity
                          resolves, then resume with regular schedule.
                          For a second occurrence of grade 3 or 4
                          toxicity, hold fluorouracil until 4 weeks
                          after toxicity resolves, then resume on a
                          4-week schedule. For a third occurrence of
                          grade 3 or 4 toxicity, discontinue treatment
                          permanently.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Hoffmann-La Roche
                          Pharmaceutical Company.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cervix Diseases/COMPLICATIONS/*PREVENTION &
                          CONTROL
MESH HEADING              Cervix Dysplasia/COMPLICATIONS/*PREVENTION &
                          CONTROL
MESH HEADING              Female
MESH HEADING              Fluorouracil/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       51-21-8 (Fluorouracil)
LAST REVISION DATE        941207
ENTRY MONTH               9301
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 930527 ACTU: 5701.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 930318
                          ACTU: 0901.
ILLINOIS                  Children's Memorial Hospital Family Clinic
                          303 East Superior Passavant Pavilion Room 823
                          Chicago, IL 60611 Contact: Baiba L Berzins RN
                          (312) 908-9636 OPEN 930121 ACTU: 2704.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 930121 ACTU: 2701.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 940502 ACTU: 7201.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 OPEN 940308 ACTU: 0104.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 930402 ACTU: 0201.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Dr Paula
                          Shuman (313) 745-1941 OPEN 931227.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          940919 ACTU: 3201.
NEW JERSEY                Univ of Med & Dentistry of NJ / Univ Hospital
                          15 South Ninth Street Newark, NJ 07107-2198
                          Contact: George Donavan Mcsherry (201)
                          268-8273 CLOSED 940513 ACTU: 2802.
NEW YORK                  St Clare's Hospital and Health Center 415
                          West 51st Street New York, NY 10019 Contact:
                          Phyllis Ristau (212) 459-8449 OPEN 930607
                          ACTU: 2204.
NEW YORK                  Memorial Hospital / Memorial Sloan-Kettering
                          Cancer Center 1275 York Avenue New York, NY
                          10021 Contact: Gloria Gilbert (212) 639-7169
                          OPEN 930723 ACTU: 2202.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 930923 ACTU: 7502.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 930301
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 930202 ACTU: 1901.
NEW YORK                  Montefiore Medical Center Adolescent AIDS
                          Program 111 East 210th Street Bronx, NY
                          10467-2490 Contact: Dina Monte (718) 882-0023
                          OPEN 931026 ACTU: 5049.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 930121
                          ACTU: 5901.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930818 ACTU: 7403.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930818 ACTU: 7402.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 930818 ACTU: 7401.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          930602 ACTU: 1102.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 930426 ACTU:
                          2401.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 930607 ACTU: 5031.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 930618
                          ACTU: 5401.
 
54
UNIQUE IDENTIFIER         NIH/00531
PROTOCOL ID NUMBERS       NIAID ACTG 193A
PROTOCOL TITLE            A Randomized, Double-Blind, Four-Arm Study
                          Comparing Combination Nucleoside, Alternating
                          Nucleoside, and Triple-Drug Therapy for the
                          Treatment of Advanced HIV Disease (CD4 <=
                          50/mm3).
VERSION NUMBER & DATE     6 (941101)
TRIAL CATEGORY            HIV Infection
PROTOCOL CHAIRS           CHAIR  Henry WK
PROTOCOL CHAIRS           CO-CHAIR  Kahn JO, Balfour HH
GENERAL DESCRIPTION       PURPOSE: To determine the relative clinical
                          efficacy of zidovudine (AZT) plus didanosine
                          (ddI), AZT plus dideoxycytidine (ddC), AZT
                          alternating monthly with ddI, and AZT/ddI
                          plus nevirapine in HIV-infected patients with
                          advanced disease.
GENERAL DESCRIPTION       RATIONALE: The rapid emergence of resistant
                          HIV strains has been observed in patients
                          receiving monotherapy with a nucleoside
                          analog or non-nucleoside reverse
                          transcriptase inhibitor. Use of combination
                          therapy with two nucleoside drugs or
                          convergent combination therapy with two
                          nucleosides and a non-nucleoside RT inhibitor
                          may minimize the evolution of these resistant
                          HIV strains. Since toxicity is a major
                          problem in patients with advanced disease who
                          are receiving combination nucleoside therapy,
                          alternating the two drugs may provide a way
                          of retaining several benefits of combination
                          therapy while minimizing the increased
                          toxicity.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either AZT/ddC, AZT/ddI, AZT
                          alternating monthly with ddI, or
                          AZT/ddI/nevirapine. Patients are evaluated at
                          week 0 and every 4 weeks thereafter for 2
                          years. Pharmacologic, virologic, and
                          macroneurologic substudies will be conducted.
                          Patients who are already enrolled on protocol
                          ACTG 193 will be given the option of
                          continuing on their originally assigned ACTG
                          193 therapy for an additional 6 months or
                          undergoing re-randomization to one of the
                          four treatment arms on ACTG 193A.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Serodiagnosis of HIV infection
                          by ELISA confirmed by an FDA-approved
                          confirmatory test such as Western blot. 2.
                          CD4 count <= 50 cells/mm3 (documented by an
                          ACTG-certified laboratory within 90 days
                          prior to study entry). 3. Either no prior
                          nucleoside therapy OR a history of prior
                          nucleoside therapy in the absence of
                          high-grade intolerance.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 42,003
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          4-Arm; Drug Combination; Comparative
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug dosing schedule.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 1292 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 908/1292 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 90 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count <= 50 cells/mm3. 3. Either no prior
                          nucleoside therapy OR a history of prior
                          nucleoside therapy in the absence of
                          high-grade intolerance. 4. Life expectancy of
                          at least 6 months. 5. Consent of parent or
                          guardian if < 18 years of age. NOTE: Patients
                          who withdrew from protocol ACTG 193 therapy
                          prior to activation of ACTG 193A are not
                          eligible. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 25000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 50 cells/mm3. ( 0 ).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          Serum amylase <= 2 x ULN. (If serum amylase >
                          2 x ULN, then pancreatic amylase <= 2 x ULN
                          or normal lipase may be substituted.)
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          during the study and for 90 days after.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: 1. Radiation
                          therapy for cutaneous Kaposi's sarcoma. 2.
                          Acupuncture.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: PCP
                          prophylaxis. Allowed: 1. Erythropoietin
                          maintenance. 2. G-CSF and GM-CSF. 3.
                          Prophylaxis for Mycobacterium avium
                          intracellulare. 4. Antifungal prophylaxis or
                          treatment with specific drugs. 5. Maintenance
                          therapy for opportunistic infection. 6.
                          Over-the-counter medications or alternative
                          therapies such as vitamins and herbs. 7.
                          Antibiotics as clinically indicated. 8.
                          Steroids for < 21 days for acute problems. 9.
                          Antipyretics, analgesics, allergy medication,
                          antidepressants, sleep medications, oral
                          contraceptives, or other appropriate
                          medications.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of recurrent grade 3 or greater
                          toxicity to AZT, ddI, or ddC on two or more
                          occasions. 2. Evidence of active pulmonary
                          disease within 6 months prior to study entry.
                          3. History of grade 3 or worse peripheral
                          neuropathy. 4. History of acute or chronic
                          pancreatitis. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 90 days after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active alcohol or drug abuse.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: More than 4 units
                          of blood in a 30-day period.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          nevirapine. Excluded within 7 days prior to
                          study entry: 1. Acute therapy for
                          opportunistic infection (maintenance therapy
                          is permitted). 2. Acute systemic therapy for
                          a nonopportunistic infection or other medical
                          condition. 3. Antiretroviral drugs other than
                          AZT, ddI, or ddC. 4. Biological response
                          modifiers. 5. d4T therapy. 6. Nucleosides
                          other than those used in the study. 7.
                          Antibiotics containing clavulanate potassium.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          chemotherapy for malignancy. 2. Acute or
                          induction therapy for opportunistic
                          infection. 3. Antiretroviral drugs other than
                          study drugs. 4. Biological response
                          modifiers. 5. Erythromycin, phenytoin,
                          phenobarbital, warfarin, or coumadin.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Abnormal baseline chest x-ray. 2. New
                          pulmonary or cardiac symptoms. 3.
                          Psychological or emotional problems
                          sufficient to prevent compliance with study
                          medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0015  Dideoxycytidine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0116  Nevirapine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 Videx
TRADE NAME OF SUBSTANCE   Drug 3 Hivid
TRADE NAME OF SUBSTANCE   Drug 4 BI-RG-587
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 5
                          Research Parkway / PO Box 5100 Wallingford,
                          CT 06492-7600 Contact: Colin McLaren (203)
                          284-6942.
MANUFACTURERS             Drug 3: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
MANUFACTURERS             Drug 4: Boehringer Ingelheim Pharmaceuticals
                          Incorporated 900 Ridgebury Road Ridgefield,
                          CT 06877 Contact: Susannah Cort (203)
                          791-6063 Contact: Maureen Myers (203)
                          798-5583.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or placebo)
                          TID. Drug 2: 200 mg (or placebo) BID. (125 mg
                          BID in patients weighi60 kg). Drug 3: 0.75 mg
                          (or placebo) TID. Drug 4: 200 mg (or placebo)
                          BID
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 600 mg. Drug 2: 400 mg
                          (250 mg in patients weighing < 60 kg). Drug
                          3: 2.25 mg. Drug 4: 400 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 100 mg capsules.
                          Drug 2: Oral; 25, 50, and 100 mg
                          chewable/dispersible tablets. Drug 3: Oral,
                          0.375 and 0.75 mg scored tablets. Drug 4:
                          Oral, 200 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 2 years.
OTHER TREATMENT INFO.     END POINT: Primary: Survival. Secondary:
                          Changes in clinical status; development of
                          HIV/AIDS-related complications; changes in
                          CD4 and CD8 counts, virologic markers, and
                          neurologic impairment.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Intercurrent event or
                          requirement for therapy that precludes
                          further use of study drugs. 3. Development of
                          a malignancy treated with systemic
                          chemotherapy. 4. Pregnancy. 5. Study
                          treatment has ceased for 90 or more days. 6.
                          Poor compliance rate. 7. Termination of the
                          study arm.
OTHER TREATMENT INFO.     MODIFICATION: Dose is held or reduced for
                          specific toxicities.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Burroughs Wellcome,
                          Bristol-Myers Squibb Company.
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Didanosine/ADMINISTRATION & DOSAGE/
                          *THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zalcitabine/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADMINISTRATION & DOSAGE/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        941207
ENTRY MONTH               9306
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 940714 ACTU: 5801.
CALIFORNIA                Children's Hospital at Los Angeles/
                          Children's AIDS Center 4650 Sunset Blvd /
                          Mail Stop #54 Los Angeles, CA 90027 Contact:
                          Antonieta Sosa (213) 669-2180 OPEN 940714
                          ACTU: 9927.
CALIFORNIA                Children's Hospital of Los Angeles /
                          Children's AIDS Center 4650 Sunset Blvd /
                          Mail Stop #54 Los Angeles, CA 90027 Contact:
                          Antonieta Sosa (213) 669-2180 OPEN 940719
                          ACTU: 9916.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          940714 ACTU: 1201.
CALIFORNIA                Harbor General / REI Lab / UCLA 1124 West
                          Carson Street Torrance, CA 90502 Contact:
                          Sally Kruger (310) 222-3848 Contact: Rick
                          Johnson OPEN 940714 ACTU: 0603.
CALIFORNIA                Olive View Medical Center / Department of
                          Medicine 14445 Olive View Drive / 2B182 Olive
                          View Medical Center Sylmar, CA 91342 Contact:
                          Betsy Manchester (818) 364-3205 OPEN 940714
                          ACTU: 0602.
CALIFORNIA                University of California San Diego 9500
                          Gilman Drive / Clinical Sciences Bldg
                          LaJolla, CA 92093-0672 Contact: Candace
                          McIvor (619) 534-7170 OPEN 940714 ACTU: 0701.
CALIFORNIA                AIDS Community Research Consortium 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harris (415) 364-5653 OPEN
                          940714 ACTU: 0505.
CALIFORNIA                Santa Clara Valley Med Ctr / ACRC 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harriss (415) 364-5653 OPEN
                          940714 ACTU: 0506.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840OPEN 940714 ACTU: 0801.
CALIFORNIA                UCSF / AIDS Clinic Ambulatory Care Center 995
                          Potrero Avenue San Francisco, CA 94110
                          Contact: David Gary (415) 476-9296 X 840OPEN
                          940714 ACTU: 0802.
CALIFORNIA                Kaiser Permanente Medical Group / Stanford
                          University 2590 Geary Boulevard San
                          Francisco, CA 94115 Contact: Gretchen Van
                          Raalte (415) 202-3482 OPEN 940714 ACTU: 0502.
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 940714
                          ACTU: 0501.
COLORADO                  University of Colorado c/o Mountain States
                          Reg Hemo Center 4200 East Ninth Avenue / Box
                          C 222 Denver, CO 80262 Contact: Sheryl
                          Giambartolomei (303) 372-1750 OPEN 940714
                          ACTU: 9813.
COLORADO                  Denver Department of Health and Hospitals /
                          Univ of CO Colorado ACTU / Campus Box B 163 /
                          4200 East Ninth Avenue Denver, CO 80262
                          Contact: M Graham Ray (303) 270-8551 OPEN
                          940714 ACTU: 6102.
COLORADO                  Rose Med Ctr / Univ of Colorado Hlth Sci Ctr
                          / Colorado ACTU Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M
                          Graham Ray (303) 270-8551 OPEN 941004 ACTU:
                          6104.
COLORADO                  University of Colorado Health Science Center
                          Colorado ACTU / Campus Box B-163 / 4200 East
                          Ninth Avenue Denver, CO 80262 Contact: M.
                          Graham Ray (303) 270-8551 OPEN 940714 ACTU:
                          6101.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 940714 ACTU: 6401.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 940714 ACTU: 5701.
DISTRICT OF COLUMBIA      HIV Center - DC General Hospital / Georgetown
                          Univ Med Ctr Kober-Cogan 110 / 3800 Reservoir
                          Road NW Washington, DC 20007-2197 Contact:
                          Karen Gammon (202) 687-1079 Contact: Fax
                          (202) 687-6476 OPEN 940714 ACTU: 5703.
DISTRICT OF COLUMBIA      Whitman-Walker Clinic / Georgetown Univ
                          Medical Center Kober-Cogan 110 / 3800
                          Reservoir Road NW Washington, DC 20007-2197
                          Contact: Karen Gammon (202) 687-1079 Contact:
                          Fax (202) 687-6476 OPEN 940714 ACTU: 5702.
DISTRICT OF COLUMBIA      Howard U Coll of Med / AIDS Minority
                          Infrastructure Program 2112 Georgia Avenue NW
                          Washington, DC 20059 Contact: Victoria Holly
                          -Trimmer (202) 806-4700 Contact: (202)
                          806-4755 OPEN 940714 ACTU: 5301.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 940714
                          ACTU: 0901.
FLORIDA                   University of South Florida / Division of
                          Infectious Disease 12901 North 30th St / Box
                          19 Tampa, FL 33612 Contact: Pat Seeley (813)
                          974-5378 OPEN 940714.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 940714
                          ACTU: 5201.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 940714 ACTU: 2701.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940714 ACTU: 2702.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941205 ACTU: 2708.
ILLINOIS                  Cook County Hospital Passavant Pavilion /
                          Room 823 / 303 East Superior Chicago, IL
                          60611 Contact: Baiba L Berzins (312) 908-9636
                          OPEN 940714 ACTU: 2705.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940714 ACTU: 2601.
INDIANA                   Methodist Hospital Of Indiana 550 North
                          University Boulevard Room 5550 Indianapolis,
                          IN 46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940714 ACTU: 2602.
MASSACHUSETTS             New England Hemophilia Center / Med Ctr of
                          Central Mass-Mem 119 Belmont Street
                          Worcester, MA 01605 Contact: Pat Forand (508)
                          793-6276 OPEN 940714 ACTU: 9110.
MASSACHUSETTS             Dartmouth-Hitchcock Med Ctr / c/o Med Ctr
                          Cntrl Mass-Mem 119 Belmont Street Worcester,
                          MA 01605 Contact: Pat Forand (508) 793-6276
                          OPEN 940714 ACTU: 9116.
MASSACHUSETTS             Massachusetts General Hospital / Harvard 55
                          Fruit Street Gray 5 Boston, MA 02114 Contact:
                          Ellen Godfrey (617) 726-5598 OPEN 940714
                          ACTU: 0101.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 OPEN 940714 ACTU: 0104.
MINNESOTA                 St Paul-Ramsey Medical Center 640 Jackson
                          Street St Paul, MN 55101 Contact: Ray Nelson
                          (612) 221-1280 OPEN 940714 ACTU: 1503.
MINNESOTA                 Hennepin County Med Clinic / Univ of
                          Minnesota Hosp Clinic 420 Delaware Street SE
                          / Room G255 Mayo Building Minneapolis, MN
                          55415 Contact: Renee St Jacques (612)
                          373-1810 OPEN 940714 ACTU: 1502.
MINNESOTA                 University of Minnesota Hospital and Clinic
                          PO Box 437 / UMHC / Harvard Street & East
                          River Road Minneapolis, MN 55455 Contact:
                          Nancy Reed (612) 625-1462 OPEN 940714 ACTU:
                          1501.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 940714 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 940714
                          ACTU: 2102.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          940714 ACTU: 3201.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Frances Tennant (402) 559-5750 OPEN
                          940714 ACTU: 1505.
NEW JERSEY                Univ of Med & Dentistry of NJ / Univ Hospital
                          15 South Ninth Street Newark, NJ 07107-2198
                          Contact: George Donavan Mcsherry (201)
                          268-8273 OPEN 940714 ACTU: 2802.
NEW JERSEY                Robert Wood Johnson University of Medicine
                          One Robert Wood Johnson Place / CN-19 Room
                          378C New Brunswick, NJ 08903-0019 Contact: Dr
                          Hugh Kim (908) 937-7680 OPEN 940714 ACTU:
                          9218.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 940714 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 940714 ACTU: 0401.
NEW YORK                  St Clare's Hospital and Health Center 415
                          West 51st Street New York, NY 10019 Contact:
                          Phyllis Ristau (212) 459-8449 OPEN 940714
                          ACTU: 2204.
NEW YORK                  Memorial Hospital / Memorial Sloan-Kettering
                          Cancer Center 1275 York Avenue New York, NY
                          10021 Contact: Gloria Gilbert (212) 639-7169
                          OPEN 940714 ACTU: 2202.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          940714 ACTU: 2201.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940714 ACTU: 1801.
NEW YORK                  Mount Sinai / Hemophilia Treatment Center One
                          Gustave Levy Place New York, NY 10029
                          Contact: Avril Gabriel (212) 241-0236 OPEN
                          940714 ACTU: 9210.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 940714 ACTU: 7501.
NEW YORK                  Harlem Hospital Center 506 Lenox Avenue /
                          Room 3101A New York, NY 10037 Contact: Robin
                          Flam (212) 939-3948 OPEN 940714 ACTU: 7502.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 940714 ACTU:
                          1905.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940714 ACTU: 1906.
NEW YORK                  North Central Bronx Hospital / Samaritan
                          Village Inc 418 Forchheimer ID / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940714 ACTU: 1907.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940714
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940714
                          ACTU: 1904.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940714 ACTU: 1903.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 940714 ACTU: 1901.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 940714
                          ACTU: 1902.
NEW YORK                  Montefiore Medical Center / Adolescent AIDS
                          Program 111 East 210th Street / NW674 Bronx,
                          NY 10467 Contact: Dina Monte (718) 882-0023
                          OPEN 940714 ACTU: 4903.
NEW YORK                  Bronx Veterans Administration Medical Center
                          130 West Kingsbridge Road Bronx, NY 10468
                          Contact: Nancy Ostrow (718) 584-9000 X
                          667Contact: (718) 584-9000 X 667OPEN 940714
                          ACTU: 1804.
NEW YORK                  North Shore University Hospital 300 Community
                          Drive Manhasset, NY 11030 Contact: Patricia
                          Gemma (516) 562-1528 OPEN 940714 ACTU: 2203.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 940714
                          ACTU: 5901.
NEW YORK                  City Hospital at Elmhurst / Mt Sinai 79-01
                          Broadway Room D1-29 Elmhurst, NY 11373
                          Contact: Dinah Reitman (718) 334-3963 OPEN
                          940714 ACTU: 1803.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          940714 ACTU: 7403.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 940714 ACTU: 7401.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          940714 ACTU: 7402.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 940714 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          940714 ACTU: 1102.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940714 ACTU: 1101.
OHIO                      Children's Hospital 700 Children's Drive
                          Columbus, OH 43205-2696 Contact: Jane Hunkler
                          (614) 722-4460 Contact: (614) 722-6050 OPEN
                          940714 ACTU: 2302.
OHIO                      Medical College of Ohio / Department of
                          Medicine 3000 Arlington Avenue Toledo, OH
                          43699 Contact: Lynn Lipton (419) 381-3729
                          Contact: (419) 381-4328 OPEN 940714 ACTU:
                          2502.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940714 ACTU: 2501.
OHIO                      Metrohealth Medical Center / Case Western
                          Reserve Univ 2500 MetroHealth Drive
                          Cleveland, OH 44109-1998 Contact: Nancy
                          Frantz (216) 459-5136 OPEN 940714 ACTU: 2503.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 940714 ACTU:
                          2401.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 940714
                          ACTU: 5401.
PENNSYLVANIA              George Washington University (Hershey
                          Satellite) 812 Fifth Avenue Pittsburgh, PA
                          15219 Contact: Elaine Carfagna (412) 622-7271
                          OPEN 940714.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 940714 ACTU: 6201.
PENNSYLVANIA              University of Pennsylvania / Girard Medical
                          Center 549 Johnson Pavillion/6073 / 36th and
                          Hamilton Walk Philadelphia, PA 19104-6073
                          Contact: Debora Dunbar (215) 349-8092 OPEN
                          940714 ACTU: 6203.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 940714 ACTU: 6202.
SOUTH CAROLINA            Medical University of SC / Infect Diseases
                          Division 807 CSB 171 Ashley Avenue
                          Charleston, SC 29425 Contact: Denise Taylor
                          (803) 782-6174 OPEN 940714 ACTU: 3205.
 
55
UNIQUE IDENTIFIER         NIH/00459
PROTOCOL ID NUMBERS       NIAID ACTG 192
PROTOCOL TITLE            A Double-Blind, Placebo-Controlled Trial of
                          Paromomycin for Treatment of
                          Cryptosporidiosis in Patients With Advanced
                          HIV Disease and CD4 Counts Under 150
                          Cells/mm3.
VERSION NUMBER & DATE     3 (941013)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Carey J
GENERAL DESCRIPTION       PURPOSE: To determine the effectiveness of
                          oral paromomycin at an initial dose of 2000
                          mg/day for 21 days compared to placebo in the
                          treatment of cryptosporidiosis in patients
                          with HIV infection. To evaluate the safety of
                          oral paromomycin at two different doses. To
                          explore whether paromomycin administered over
                          a longer period provides additional benefit.
GENERAL DESCRIPTION       RATIONALE: In previous studies, patients with
                          cryptosporidiosis demonstrated dramatic
                          improvement with paromomycin therapy.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either placebo or paromomycin (2000
                          mg/day) for 3 weeks. After the initial
                          double-blind phase, all patients receive
                          open-label paromomycin (2000 mg/day) for 3
                          weeks. Following 6 weeks of therapy, patients
                          who do not achieve a complete response
                          receive 4000 mg/day for an additional 3
                          weeks, while complete responders continue
                          receiving 2000 mg/day for an additional 3
                          weeks. Complete or partial responders after 9
                          weeks may receive 16 additional weeks of
                          optional maintenance therapy at the dose at
                          which their response was achieved. Treatment
                          continues for up to 25 weeks total. Patients
                          are followed at weeks 1, 3, 4, 6, 7, and 9,
                          and then at 2-4 week intervals.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Cryptosporidiosis / diarrhea.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive. 2. CD4 count
                          <= 150 cells/mm3. 3. Cryptosporidial diarrhea
                          for at least 4 of 7 days prior to study
                          entry, defined by four or more loose stools
                          per day. 4. Cryptosporidium oocysts
                          documented in 2 consecutive stool samples
                          within 21 days prior to study entry.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    IND 40,711
STUDY DESIGN              Multicenter; Double-Blind;
                          Placebo-Controlled; Randomized; 2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 68 patients. (34 per
                          treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 25 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 27/68 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 20 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Advanced HIV disease. 2. Diarrhea
                          presumptively caused by Cryptosporidia.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 150 cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE: < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 40.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral therapy. 2. Macrolides for
                          disseminated Mycobacterium avium. 3.
                          Atovaquone for toxoplasmosis. 4. Other
                          antimicrobials for concurrent infections. 5.
                          Lomotil, Imodium, or deodorized opium
                          tincture in a standardized regimen for
                          diarrhea.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Paromomycin at >
                          1 g/day for >= 14 days prior to study entry.
                          Excluded within 14 days prior to study entry:
                          1. Agents with putative anticryptosporidial
                          activity (such as spiramycin, diclazuril,
                          letrazuril, or bovine colostrum), with the
                          exception of macrolides that are permitted
                          for other indications. 2. Octreotide acetate
                          (Sandostatin).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded during the
                          first 9 weeks of study: 1. Agents with
                          putative anticryptosporidial activity (such
                          as spiramycin, diclazuril, letrazuril, or
                          bovine colostrum). 2. Octreotide acetate
                          (Sandostatin). 3. Antidiarrheals other than
                          those specifically allowed. 4. Clarithromycin
                          if initiated at 500 mg or higher or
                          azithromycin if initiated at 600 mg or
                          higher.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Hypersensitivity to aminoglycosides. 2.
                          Inability to swallow capsules. 3. Active
                          infection due to other enteric pathogens.
                          Previous diagnosis of CMV or MAC infection
                          permitted if patient is currently stabilized
                          on a therapeutic regimen (clarithromycin up
                          to 500 mg BID or azithromycin up to 600 mg
                          daily). 4. Other known causes for diarrhea
                          (e.g., malabsorption syndrome,
                          gastrointestinal Kaposi's sarcoma).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0188  Paromomycin
TRADE NAME OF SUBSTANCE   Drug 1 Humatin
MANUFACTURERS             Drug 1: Warner Lambert Company / Parke-Davis
                          Research 2800 Plymouth Road Ann Arbor, MI
                          48105 Contact: John Bender (313) 996-7297.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 500 mg (or placebo)
                          QID during weeks 1 through 3, followed by 500
                          mg QID for all patients during weeks 4
                          through followed by either 500 mg QID (in
                          patients with a complete respafter 6 weeks)
                          or 1000 mg QID (in patients without a
                          complete response after 6 weeks) during weeks
                          7 through 9; followed by optional maintenance
                          (in patients with a complete or partial
                          response) during weeks 10 through 25, at the
                          dose at which the response was achieved
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 2000 - 4000 mg,
                          depending on response
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 250 mg capsules
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 9 weeks, with
                          possible continuation for 16 additional
                          weeks.
OTHER TREATMENT INFO.     END POINT: Response rate, drug tolerance,
                          parasitologic response.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Clinically
                          significant adverse experiences (e.g.,
                          ototoxicity). 2. Lack of efficacy. 3.
                          Progressive rise in serum creatinine to 2 X
                          baseline for > 4 days, or serum creatinine >
                          1.5 mg/dl despite adequate hydration. 4.
                          Continuation would jeopardize patient's
                          health.
OTHER TREATMENT INFO.     MODIFICATION: Patients on 4000 mg/day study
                          drug who experience increased diarrhea,
                          nausea, or vomiting decrease dose to 2000
                          mg/day.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cryptosporidiosis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Paromomycin/*THERAPEUTIC USE
CAS REGISTRY NUMBER       7542-37-2 (Paromomycin)
LAST REVISION DATE        941207
ENTRY MONTH               9309
CALIFORNIA                Kaiser Permanente Medical Group / Stanford
                          University 2590 Geary Boulevard San
                          Francisco, CA 94115 Contact: Gretchen Van
                          Raalte (415) 202-3482 OPEN 931020 ACTU: 0502.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 931006
                          ACTU: 0901.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 931223 ACTU: 2701.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941017 ACTU: 2708.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940201 ACTU: 2702.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940513 ACTU: 2601.
INDIANA                   Methodist Hospital Of Indiana 550 North
                          University Boulevard Room 5550 Indianapolis,
                          IN 46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940523 ACTU: 2602.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 931109 ACTU:
                          2101.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 930916 ACTU: 0401.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          931006 ACTU: 2201.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 931227 ACTU: 7501.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 931101
                          ACTU: 1902.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 931101 ACTU: 1901.
NEW YORK                  Montefiore Medical Center Adolescent AIDS
                          Program 111 East 210th Street Bronx, NY
                          10467-2490 Contact: Dina Monte (718) 882-0023
                          OPEN 930916 ACTU: 5049.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 940825 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          940214 ACTU: 1102.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 931006
                          ACTU: 2301.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 931006 ACTU: 2501.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 940113 ACTU:
                          2401.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 941004
                          ACTU: 5401.
 
56
UNIQUE IDENTIFIER         NIH/00467
PROTOCOL ID NUMBERS       NIAID ACTG 188
PROTOCOL TITLE            Neurodevelopmental and Neurological Study of
                          Infants and Children With HIV-1 Infection and
                          AIDS in Clinical Trials.
VERSION NUMBER & DATE     1 (920925)
TRIAL CATEGORY            Epidemiology
TRIAL CATEGORY            Child
PROTOCOL CHAIRS           CHAIR  Wilson B
PROTOCOL CHAIRS           CO-CHAIR  Fletcher J, Belman A
GENERAL DESCRIPTION       PURPOSE: To establish the validity of the
                          NIMH Neurodevelopmental and Neurological
                          Assessment Battery. To evaluate
                          neurodevelopment in infants and children with
                          HIV-related CNS disease. To evaluate
                          multicultural assessment issues in multisite
                          studies. To describe the nature of impaired
                          developmental abilities and the different
                          course of HIV disease in infants and
                          children.
GENERAL DESCRIPTION       RATIONALE: The assessment of children who
                          sustain CNS insult requires approaches that
                          differ in several ways from adult-based
                          assessment. The rapid changes that occur in
                          the developing CNS as well as in behavior
                          reflect underlying processes of growth and
                          development.
GENERAL DESCRIPTION       METHODOLOGY: This study will be conducted as
                          a nested substudy within ACTG 152. It will
                          include 225 HIV-infected patients from ACTG
                          152, as well as an additional 450
                          non-infected participants recruited for two
                          comparison groups, one consisting of
                          seronegative infants and children with
                          perinatal exposure to HIV and a second group
                          without perinatal exposure to HIV. A
                          neurological assessment battery will evaluate
                          the following domains: growth, sensory, tone,
                          motor, posture, locomotion, hand use, deep
                          tendon reflexes, abnormal movements,
                          language, and behavior. Participants will be
                          asked to do different kinds of activities
                          such as talking, listening, and drawing, and
                          to play games that involve walking, jumping,
                          concentration, and memory. Spanish-speaking
                          children will be evaluated using the Spanish
                          translations of the battery. All participants
                          will be assessed at clinic visits and
                          followed for a minimum of 2 years.
PROTOCOL PHASE            Epidemiology
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Participants must meet the following
                          criteria. 1. Belong to one of the following
                          categories: o Infants and children enrolled
                          on ACTG 152; o Other infants and children who
                          are HIV seronegative WITHOUT perinatal HIV
                          exposure; o Other infants and children who
                          are HIV seronegative WITH perinatal HIV
                          exposure. NOTE: Infants < 15 months of age
                          with perinatal HIV exposure may have a
                          positive serological test for HIV antibody at
                          enrollment, but a negative test must be
                          obtained once the child reaches the age of 15
                          months. 2. Recruited at sites designated to
                          conduct this observational study.
ELIGIBILITY               ARC. AIDS. HIV Seronegative.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Nested Study
PROTOCOL DETAILS          STUDY INTENT: Epidemiology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 675 patients. (225
                          patients from ACTG 152; 450 other
                          participants for comparison)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 141/675 (941207).
PROTOCOL DETAILS          STUDY DURATION: 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Participants must
                          meet the following criteria: 1. Infants and
                          children on ACTG 152 OR other infants and
                          children who are HIV seronegative without
                          perinatal HIV exposure OR other infants and
                          children who are HIV seronegative with
                          perinatal HIV exposure. NOTE: Infants < 15
                          months of age with perinatal HIV exposure may
                          have a positive serological test for HIV
                          antibody at enrollment, but a negative test
                          must be obtained once the child reaches the
                          age of 15 months. 2. Recruited at sites
                          designated to conduct this observational
                          study. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: Non-applicable percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: Non-applicable g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: Non-applicable cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: Non-applicable platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CD4/CD8 RATION: Non-applicable.
PATIENT INCLUSION CRIT.   BILIRUBIN: Non-applicable mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): Non-applicable.
PATIENT INCLUSION CRIT.   SGPT(ALT): Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE: Non-applicable.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: Non-applicable ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: Non-applicable.
PATIENT AGE               AGE: 03 Months - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Excluded in
                          participants enrolled in ACTG 152: History of
                          pancreatitis within one year prior to study
                          entry associated with compatible symptoms.
                          Excluded in ALL participants: History of
                          uncontrolled seizure disorder. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 19 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Ongoing drug or alcohol use.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded in
                          participants in comparison groups:
                          Chemotherapy for malignancy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Excluded in participants
                          enrolled in ACTG 152: 1. Active malignancy.
                          2. Grade 3 or higher peripheral neuropathy.
                          3. Cardiomyopathy. 4. Blindness or deafness.
                          5. Pancreatitis. Excluded in participants in
                          the comparison groups: 1. Active malignancy.
                          2. Peripheral neuropathy defined by absent
                          deep tendon reflexes, severe motor weakness,
                          paralysis, severe paresthesia, or sensory
                          loss.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Inablilty to be followed at the
                          site of enrollment or another ACTU for 104
                          weeks.
OTHER TREATMENT INFO.     END POINT: Neurodevelopmental and
                          neurological status.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG).
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS/ETIOLOGY
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS/ETIOLOGY
MESH HEADING              Adolescence
MESH HEADING              Central Nervous System Diseases/
                          *COMPLICATIONS/EPIDEMIOLOGY/ETIOLOGY
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Peripheral Nervous System Diseases/
                          *COMPLICATIONS/EPIDEMIOLOGY/ETIOLOGY
LAST REVISION DATE        941207
ENTRY MONTH               9402
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          940105 ACTU: 1801.
 
57
UNIQUE IDENTIFIER         NIH/00446
PROTOCOL ID NUMBERS       NIAID ACTG 185
PROTOCOL TITLE            A Phase III Randomized, Double-Blind,
                          Controlled Study of the Use of Anti-HIV
                          Immune Serum Globulin (HIVIG) for the
                          Prevention of Maternal-Fetal HIV Transmission
                          in Pregnant Women and Newborns Receiving
                          Zidovudine (AZT).
VERSION NUMBER & DATE     2 (930712)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Pregnancy
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the effect of anti-HIV
                          immune serum globulin (HIVIG) versus immune
                          globulin (IVIG) administered during pregnancy
                          and to the newborn, in combination with
                          zidovudine (AZT) administered intrapartum and
                          to the newborn, on incidence of HIV infection
                          in infants born to HIV-infected women who
                          received AZT during pregnancy for medical
                          indications.
GENERAL DESCRIPTION       RATIONALE: Vertical transmission of HIV from
                          mother to child may occur before, during, or
                          after parturition (via breast-feeding). It is
                          believed that therapy administered both
                          during pregnancy and intrapartum may help
                          prevent vertical transmission. Additionally,
                          adjunctive short-term antiretroviral therapy
                          for the newborn, following the intensive
                          viral exposure presumed to occur at birth,
                          may be necessary.
GENERAL DESCRIPTION       METHODOLOGY: Pregnant women who are currently
                          receiving AZT are randomized at 20-30 weeks
                          of gestation to begin receiving either HIVIG
                          or IVIG every 28 days up to delivery. Within
                          12 hours after birth, the infant receives an
                          infusion of matching study drug. During
                          labor, all women receive an intravenous
                          loading dose of AZT administered over 1 hour,
                          followed by continuous infusion during the
                          intrapartum period until the umbilical cord
                          is clamped. All infants receive AZT syrup
                          every 6 hours, beginning as soon as oral
                          fluids are tolerated but within 8-12 hours
                          after birth and continuing for 6 weeks. Women
                          are followed until 26 weeks postpartum.
                          Infants are followed at weeks 1, 2, 4, and
                          then every 4 weeks through week 24, every 12
                          weeks through week 60, at week 78 (18
                          months), and at week 104 (24 months).
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA, with appropriate confirmatory test,
                          positive p24 antigen, or positive viral
                          culture (blood or CSF). 2. Receiving AZT
                          during current pregnancy for any of the
                          following medical indications: o CD4 count <=
                          500 cells/mm3 at study entry o CD4 count <=
                          500 cells/mm3 at time AZT was initiated o
                          History of AIDS-defining illness. 3.
                          Gestational age between 20 and 30 weeks based
                          on sonogram or menstrual history confirmed by
                          first pelvic exam.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    BB-IND 4293
STUDY DESIGN              Randomized; Controlled; Multicenter; Drug
                          Combination; 2-Arm; Double-Blind
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination drug therapy,
                          Immunotherapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 800 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Women: Until 6
                          months postpartum. Infants: 2 years.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 118/800 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. Been
                          receiving AZT during current pregnancy for
                          medical indications. 3. Gestational age
                          between 20 and 30 weeks. 4. Intention to
                          carry pregnancy to term. 5. Available venous
                          access (placement of central line or Hickman
                          catheter not indicated for study purposes).
                          6. Willingness to be followed by a
                          participating site for study duration. NOTE:
                          Father of fetus (if available after a
                          reasonable attempt to contact him) must also
                          provide informed consent. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 70 ml/min. (if
                          creatinine value not available).
PATIENT INCLUSION CRIT.   OTHER: Urine protein < 2+ by dipstick or < 4
                          g protein in 24-hour urine collection.
PATIENT AGE               AGE: 13 Years - 60 Years.
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Pregnant.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Women -
                          Medications as required for obstetrical
                          management of HIV infection (e.g., acyclovir,
                          ketoconazole, isoniazid, antibiotics, or
                          other antiretroviral therapy if intolerant or
                          failing on AZT), unless specifically
                          excluded. 2. Infants - Drug treatment for
                          signs of drug withdrawal (phenobarbital,
                          chlorpromazine, tincture of opium, paregoric
                          or Valium). 3. Infants - Medications as
                          indicated for management of an HIV-exposed
                          infant (e.g., hepatitis B vaccine, syphilis
                          treatment, Pneumocystis carinii pneumonia
                          prophylaxis).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Evidence of pre-existing fetal anomalies
                          (e.g., anencephaly, renal agenesis, or
                          Potter's syndrome) that may result in a high
                          probability that the fetus-infant would not
                          survive to the end of the study period. 2.
                          Chorionic villus sampling (CVS) or
                          percutaneous umbilical blood sampling (PUBS)
                          occurring in this pregnancy prior to study
                          entry. 3. Illness associated with excessive
                          protein loss, e.g., chronic diarrhea with no
                          documented weight gain in a 3-month period
                          during pregnancy. 4. Pre-existing conditions
                          such as hypogammaglobulinemia or immune
                          thrombocytopenia that are felt to require
                          IVIG therapy. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   SEX: MALE
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Not pregnant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Receipt of
                          anti-HIV vaccines or passive immunotherapy
                          with HIVIG or IVIG during this pregnancy
                          prior to study entry. 2. Receipt of
                          antiretroviral agents other than AZT during
                          this pregnancy prior to study entry (e.g.,
                          rCD4, CD4-IgG, d4T, ddC, ddI).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Illness
                          associated with excessive protein loss, e.g.,
                          severe proteinuria (protein >= 4 g protein in
                          a 24-hour urine collection).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0087  Anti-HIV immune serum
                          globulin (Human)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0022  Globulin, immune
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 1 HIVIG
TRADE NAME OF SUBSTANCE   Drug 2 IVIG
TRADE NAME OF SUBSTANCE   Drug 3 Retrovir
MANUFACTURERS             Drug 1: North American Biologicals
                          Incorporated 16500 NW 15th Avenue Miami, FL
                          33169 Contact: Dr Christine Sapan (305)
                          625-5303.
MANUFACTURERS             Drug 2: Cutter Biological Miles Incorporated
                          4th & Parker Streets PO Box 1986 Berkeley, CA
                          94701 Contact: Dr Ralph Rousell (510)
                          420-5120.
MANUFACTURERS             Drug 3: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: During pregnancy:
                          200 mg/kg q 28 days beginning
                          betweengestational weeks 20 and 30 and
                          continuing until delivery. Infant: 200 mg/kg
                          within 12 h after birth. Drug 2: During
                          pregnancy: 200 mg/kg q 28 days beginning
                          betweengestational weeks 20 and 30 and
                          continuing until delivery. Infant: 200 mg/kg
                          within 12 h after birth. Drug 3: Intrapartum:
                          2.0 mg/kg IV (loading dose) followed by
                          1.mg/kg/hr continuous infusion until
                          umbilical cord is clamped. Infant: 2.0 mg/kg
                          PO q 6 h (beginning as soon as infant can
                          toloral fluids within 8-12 h after birth)
                          until week 6
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 3: Infant: 8.0 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV); 500,
                          2000, 2500, and 12500 mg vials. Drug 2:
                          Intravenous (IV); 500, 2500, and 12500 mg
                          vials. Drug 3: Intravenous - 200 mg vials;
                          oral - 2400 mg bottles
OTHER TREATMENT INFO.     END POINT: Definitive HIV infection in the
                          infant.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue HIVIG or
                          IVIG treatment for the following reasons: 1.
                          Severe allergic reaction to infusion such as
                          exfoliative erythroderma, anaphylaxis, or
                          vascular collapse. 2. A clinical condition
                          that is considered incompatible with life. 3.
                          At the request of the patient, parent or
                          guardian, investigator, FDA, pharmaceutical
                          company, or IND sponsor. Infants discontinue
                          AZT treatment for the following reasons: 1.
                          Immediate life-threatening or clinical
                          condition that is considered incompatible
                          with life. 2. Grade 3 toxicity or
                          unacceptable laboratory values. 3. Severe
                          allergic reaction such as exfoliative
                          erythroderma, anaphylaxis, or vascular
                          collapse. 4. Evidence of HIV infection. 5. At
                          the request of the parent or guardian,
                          investigator, FDA, pharmaceutical company, or
                          IND sponsor.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), National Institute of Child
                          Health and Development.
MESH HEADING              AIDS-Related Complex/*THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*THERAPY/TRANSMISSION
MESH HEADING              Human
MESH HEADING              Immunization, Passive
MESH HEADING              Immunoglobulins, Intravenous/*THERAPEUTIC USE
MESH HEADING              Infant
MESH HEADING              Middle Age
MESH HEADING              Pregnancy
MESH HEADING              Pregnancy Complications, Infectious
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Immunoglobulins, Intravenous)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        941207
ENTRY MONTH               9311
CALIFORNIA                UCLA Medical Center / Pediatrics 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          940804 ACTU: 3601.
CALIFORNIA                University of Southern California Medical
                          Center Pediatric Pavillion / Room 3D14 / 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          940804.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Sheri Jo
                          Smith (Adults) (313) 993-2681 Contact:
                          Charnell Cromer (Pediatrics) (313) 745-5565
                          OPEN 940804.
OTHER                     University of Puerto Rico / University
                          Pediatric Hospital 4th Floor South Wing Room
                          4B-45 / GPO Box 365067 San Juan, PR
                          00936-5067 Contact: Carmen Rivera (809)
                          759-9595 Contact: (809) 765-1979 X 724OPEN
                          940804 ACTU: 6601.
 
58
UNIQUE IDENTIFIER         NIH/00389
PROTOCOL ID NUMBERS       NIAID ACTG 180
PROTOCOL TITLE            Pharmacokinetics, Safety, Tolerance, and
                          Activity of Nevirapine (BI-RG-587) Alone and
                          in Combination With AZT in Mildly to
                          Moderately Symptomatic HIV-I Infected
                          Children.
VERSION NUMBER & DATE     1 (910821) Final
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
TRIAL CATEGORY            Child
PROTOCOL CHAIRS           CHAIR  Sullivan J
PROTOCOL CHAIRS           CO-CHAIR  Luzuriaga K
GENERAL DESCRIPTION       PURPOSE: Monotherapy phase: To evaluate and
                          compare the safety, tolerance,
                          pharmacokinetics, and preliminary activity of
                          nevirapine administered alone in mildly to
                          moderately symptomatic HIV-infected children
                          ages 2 months to less than 18 years; to
                          evaluate and compare the safety, tolerance,
                          and pharmacokinetics of nevirapine in
                          HIV-infected children ages 1 day to less than
                          2 months. Combination therapy phase: To
                          evaluate and compare the safety, tolerance,
                          pharmacokinetics, and preliminary activity of
                          nevirapine administered in combination with
                          zidovudine (AZT) in mildly to moderately
                          symptomatic HIV-infected children ages 2
                          months to less than 18 years.
GENERAL DESCRIPTION       RATIONALE: Compounds with reverse
                          transcriptase inhibitory activity that are
                          more potent and less toxic than the
                          nucleoside analogs are needed. Nevirapine
                          (BI-RG-587) has shown in vitro inhibitory
                          activity against HIV-1 reverse transcriptase
                          and has shown a synergistic inhibition of
                          HIV-1 replication when combined with
                          zidovudine (AZT) in a plaque reduction assay.
GENERAL DESCRIPTION       METHODOLOGY: Sixty mildly to moderately
                          symptomatic HIV-infected children (five
                          patients in each of four age groups) will
                          receive oral nevirapine at 7.5, 30, or 120
                          mg/m2 daily for 168 days. If preliminary
                          activity is demonstrated and toxicity is
                          acceptable after 84 days of treatment in the
                          three oldest age groups (ages 2 months - less
                          than 2 years, ages 2 years - less than 13
                          years, and ages 13 years - less than 18
                          years), children ages 1 day - less than 2
                          months will receive one of the three doses of
                          nevirapine. Additionally, 15 additional
                          patients (five in each of three age groups)
                          will receive 180 mg/m2 zidovudine in
                          combination with 120 mg/m2 nevirapine. At the
                          end of 24 weeks of combination therapy,
                          patients discontinue zidovudine for 2 weeks
                          while remaining on nevirapine, in order for
                          pharmacokinetic sampling to be done. Children
                          will be enrolled sequentially by decreasing
                          age and increasing nevirapine dose.
PROTOCOL PHASE            Unspecified
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Evidence of HIV-1 infection as
                          follows: o Children younger than 15 months
                          must have one positive peripheral blood viral
                          isolation OR one detectable serum p24 antigen
                          test (at least 30 pg/ml). o Children older
                          than 15 months must have Either of the above
                          criteria OR Two positive tests for serum HIV
                          antibodies (at least 72 hours apart), both
                          determined by ELISA or one of the two
                          determined by Western blot. 2. Children ages
                          1 day to less than 2 months may be enrolled
                          regardless of CD4 count and symptoms. 3.
                          Children ages 2 months to less than 18 years
                          must have absolute CD4 cell counts within
                          28-42 days prior to entry as follows: o Ages
                          2-11 months - < 1500/mm3 o Ages 12-23 months
                          - < 750/mm3 o Ages 24 months and over - <
                          500/mm3 AND/OR Have one or more of the
                          following symptoms: o HIV encephalopathy o
                          Lymphocytic interstitial pneumonitis
                          (provided patient is not on steroids or
                          requires supplemental oxygen or has a
                          pretreatment paO2 < 70 mm Hg) o Hepatitis
                          considered secondary to HIV (patients with
                          hemophilia cannot have hepatitis as the sole
                          inclusion criteria) o Cardiomyopathy o
                          Nephropathy (defined as persistent
                          proteinuria, i.e., > 500 mg/24 hours in
                          children 12 years and older and > 300 mg/24
                          hours in children younger than 12 years),
                          with a normal creatinine clearance o
                          Hematologic disorders including absolute
                          neutrophil count < 1500/mm3 but > 800/mm3 or
                          platelet count < 150000 on 2 occasions more
                          than one week apart or hemolytic anemia o
                          Dermatologic disease considered secondary to
                          HIV o One or more episodes of herpes zoster
                          or herpes simplex during the patient's life
                          that occur simultaneously with HIV positivity
                          o Diarrhea defined as more than 4 watery
                          stools per day for > 4 weeks in the absence
                          of a defined infection or 2 or more episodes
                          of severe diarrhea within 2 months requiring
                          hospitalization for rehydration o Parotitis
                          (chronic parotid enlargement for 8 weeks or
                          longer after diagnosis of HIV o Organomegaly
                          (hepatomegaly or splenomegaly) o History of
                          recurrent bacterial infections (6 or more
                          episodes within 2 years) other than serious
                          bacterial infections (bacteremia, meningitis,
                          pneumonia, abscess of internal organ,
                          bone/joint infections).
ELIGIBILITY               AIDS. p24+. HIV Seropositive. ARC. ASYM.
OTHER PROTOCOL NUMBERS    882
STUDY DESIGN              Multicenter; Open Label; Drug Tolerance; Drug
                          Combination
PROTOCOL DETAILS          STUDY INTENT: Combination and single drug
                          therapy, Combination and single
                          pharmacokinetics, Drug efficacy, Drug safety,
                          Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 35 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 29/35 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 7 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. A positive Polymerase
                          Chain Reaction (PCR) is not acceptable as the
                          sole evidence of HIV infection. Three out of
                          five children in each age and dose group must
                          have a serum p24 antigen level of 70 pg/ml or
                          greater and/or a plasma viral titer of 50
                          TCID/ml or greater prior to study entry. 2.
                          Ability to be followed by their original
                          trial center for the duration of the trial.
                          3. Consent of parent or guardian. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: > 24 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl. Transfusion permitted.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
                          Exclusion: HIV-associated thrombocytopenia.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN mg/dl. ULN = upper limit
                          of normal.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophil count > 750
                          cells/mm3
PATIENT AGE               AGE: 01 Days - 17 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study. Negative
                          pregnancy test.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. IV
                          gammaglobulin therapy. 2. Medications for PCP
                          prophylaxis (e.g., TMP / SMX, dapsone,
                          aerosolized and iv pentamidine). 3.
                          Fluconazole.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with
                          prior participation in this trial are
                          excluded. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: No abstinence or no
                          agreement to use barrier methods of birth
                          control / contraception during the study.
                          Pregnant.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active alcohol or drug abuse
                          to impair compliance with the protocol.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: More than 6 weeks
                          of prior zidovudine (AZT) therapy or more
                          than 6 weeks of any other antiretroviral
                          therapy. Excluded within 7 days prior to
                          study entry: AZT (in monotherapy groups
                          only). Excluded within 4 weeks prior to study
                          entry: 1. Other approved or investigational
                          antiretroviral agents. 2. All other
                          investigational agents. 3. Glucocorticoids
                          and steroid hormones. 4. Dicumarol, warfarin,
                          and other anticoagulants. 5. Digitoxin. 6.
                          Valproic acid. 7. Tolbutamide. 8.
                          Doxycycline. 9. Chloramphenicol. 10.
                          Isoniazid. 11. Phenobarbital and other
                          barbiturates.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          approved or investigational antiretroviral
                          agents. 2. All other investigational agents
                          (except fluconazole). 3. Glucocorticoids and
                          steroid hormones. 4. Dicumarol, warfarin, and
                          other anticoagulants. 5. Digitoxin. 6.
                          Valproic acid. 7. Tolbutamide. 8.
                          Doxycycline. 9. Chloramphenicol. 10.
                          Isoniazid. 11. Phenobarbital and other
                          barbiturates. 12. Hepatotoxic drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Lymphocytic interstitial pneumonitis if
                          steroid-dependent or requiring supplemental
                          oxygen or with a pretreatment paO2 < 70 mm
                          Hg. 2. Opportunistic or serious bacterial
                          infections within 28 days prior to entry. 3.
                          Demonstrated intolerance to zidovudine prior
                          to administration of nevirapine (in patients
                          enrolled in the combination therapy phase of
                          the study). 4. CDC classification of P-2D
                          (secondary infectious diseases) and/or P-2E
                          (secondary cancers). 5. Pre-existing
                          malignancies.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unable to be followed by their
                          original trial center for the duration of the
                          study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 1 BI-RG-587
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Boehringer Ingelheim Pharmaceuticals
                          Incorporated 900 Ridgebury Road Ridgefield,
                          CT 06877 Contact: Susannah Cort (203)
                          791-6063 Contact: Maureen Myers (203)
                          798-5583.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 7.5, 30, or 120
                          mg/m2 daily for 168 days. Drug 2: 180 mg/m2 q
                          6 hr for 168 days
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 7.5, 30, or 120 mg/m2.
                          Drug 2: 720 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 5 mg/ml
                          suspension and 2.5, 12.5, and 50 mg tablets.
                          Drug 2: Oral, 10 mg/ml syrup or 100 mg
                          tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Safety, tolerance,
                          pharmacokinetics, and preliminary activity of
                          nevirapine alone and in combination with
                          zidovudine.
OTHER TREATMENT INFO.     DISCONTINUE: Patients will be discontinued
                          from treatment for the following reasons: 1.
                          Occurrence of an intolerable adverse event.
                          2. Recurrent grade 3 or 4 toxicity despite
                          maximal dose reductions. 3. Significant
                          noncompliance with protocol requirements.
OTHER TREATMENT INFO.     MODIFICATION: Monotherapy: For grade 3 or 4
                          toxicity, hold nevirapine until return to
                          grade 2 or better, then resume at 50% dose.
                          Combination therapy: For recognizable grade 3
                          or 4 toxicity or intolerable grade 2 toxicity
                          to either neveripine or AZT, hold that drug
                          until return to grade 1 or baseline, then
                          resume at 50% dose; continue the other study
                          drug. If toxicity cannot be attributed to
                          either drug, discontinue both medications
                          until resolution to grade 1 or baseline, then
                          resume both drugs.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Boehringer Ingelheim
                          Pharmaceutical Incorporated.
MESH HEADING              AIDS-Related Complex/DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY/METABOLISM
MESH HEADING              Adolescence
MESH HEADING              Antiviral Agents/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Child
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY/METABOLISM
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Pyridines/PHARMACOKINETICS/*THERAPEUTIC USE
MESH HEADING              Reverse Transcriptase/ANTAGONISTS & INHIB
MESH HEADING              Zidovudine/PHARMACOKINETICS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       EC 2
LAST REVISION DATE        941207
ENTRY MONTH               9112
CALIFORNIA                UCLA School of Medicine / Department of
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024 Contact: Dr Yvonne J Bryson (310)
                          825-5235 OPEN 940804.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          940804 ACTU: 1201.
CONNECTICUT               University of Connecticut Health Center /
                          Dept of Pediatrics 263 Farmington Avenue
                          Farmington, CT 06032 Contact: Dr James
                          Robinson (203) 679-2221 OPEN 940804.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 940804 ACTU: 4201.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street Springfield,
                          MA 01199 Contact: Dr Barbara Stechenberg
                          (413) 784-5379 OPEN 940804.
MASSACHUSETTS             University of Massachusetts Medical Center /
                          Biotech II 373 Plantation Street Room 318
                          Worcester, MA 01605 Contact: John Sullivan
                          (508) 856-6282 OPEN 940804.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 940804 ACTU: 2801.
 
59
UNIQUE IDENTIFIER         NIH/00413
PROTOCOL ID NUMBERS       NIAID ACTG 179
PROTOCOL TITLE            Comparison of Two Dosage Regimens of Oral
                          Dapsone for Prophylaxis of Pneumocystis
                          Carinii Pneumonia in Pediatric HIV Infection.
VERSION NUMBER & DATE     3 (931129)
TRIAL CATEGORY            Child
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  McIntosh K
PROTOCOL CHAIRS           CO-CHAIR  Cooper E
GENERAL DESCRIPTION       PURPOSE: Primary: To compare the toxicity of
                          daily versus weekly dapsone in HIV-infected
                          infants and children; to study the
                          pharmacokinetics of orally administered
                          dapsone in HIV-infected infants and children.
                          Secondary: To obtain information on the rate
                          of Pneumocystis carinii pneumonia ( PCP )
                          breakthrough in children receiving two
                          different dose regimens of dapsone.
GENERAL DESCRIPTION       RATIONALE: Prophylaxis for Pneumocystis
                          carinii pneumonia ( PCP ) is recommended for
                          all HIV-infected children considered to be at
                          high risk. Approximately 15 percent of
                          children are intolerant to trimethoprim /
                          sulfamethoxazole, the first choice drug for
                          PCP prophylaxis. Since many children are also
                          unable to take or tolerate aerosolized
                          pentamidine, dapsone is a second choice for
                          PCP prophylaxis. The most favorable dose
                          regimen for dapsone has not been established.
GENERAL DESCRIPTION       METHODOLOGY: Ninety-six HIV-infected infants
                          and children who are intolerant to
                          trimethoprim / sulfamethoxazole ( TMP / SMX )
                          are randomized to receive oral dapsone either
                          at 2 mg/kg once daily or at 4 mg/kg once
                          weekly. Treatment continues until the last
                          patient enrolled has received at least 3
                          months of therapy. Blood samples are drawn
                          between weeks 4 and 8, at weeks 12 and 24,
                          and every 3 months thereafter during dapsone
                          administration.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Evidence of HIV infection. o
                          Children 15 months of age and older must have
                          a positive viral culture (blood or CSF) OR
                          serum p24 antigen = or > 30 pg/ml OR two
                          positive tests for HIV antibody by ELISA,
                          with one test confirmed by Western blot. o
                          Children younger than 15 months whose only
                          laboratory evidence of HIV infection is a
                          positive antibody test must also have a
                          positive viral culture (blood or CSF) OR an
                          AIDS-defining illness by CDC criteria. 2.
                          Risk of developing PCP with prophylaxis
                          requirement as defined in MMWR guidelines. 3.
                          Known intolerance to TMP / SMX, such as
                          occurrence of leukopenia, thrombocytopenia,
                          or cutaneous reaction.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    IND 38,841
STUDY DESIGN              Dose Comparison; Randomized; Open Label;
                          2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug safety,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 96 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 61/96 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 50 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Evidence of HIV infection. 2. Risk
                          of developing PCP. 3. Known intolerance to
                          TMP / SMX. 4. Consent of parent or guardian.
                          Patients entering this study may be
                          co-enrolled in other ACTG pediatric studies.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 5 x ULN mg/dl. (ULN = upper
                          limit of normal.)
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophil count > 750
                          cells/mm3. Methemoglobin < 15 percent.
PATIENT AGE               AGE: 01 Months - 12 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Rifampin
                          and rifampin derivatives for up to 1 week
                          during the study. 2. Rifabutin or other drugs
                          that could alter dapsone metabolism (if
                          prescribed by the child's primary care
                          physician).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Serious or life-threatening reactions to TMP
                          / SMX (e.g., anaphylaxis, Stevens-Johnson
                          syndrome, hypotension) that would
                          contraindicate therapy with sulfa drugs.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 29 Days. 13 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: RBC transfusion
                          within 4 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior dapsone.
                          2. Rifampin, rifampin derivatives, or oxidant
                          drugs within 1 week prior to study entry. 3.
                          TMP / SMX within 7 days prior to study entry
                          (and toxicity must be clearly resolving).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Rifampin,
                          rifampin derivatives, or oxidant drugs for
                          more than 1 week.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Glucose-6-phosphate dehydrogenase deficiency.
                          2. Known allergy to dapsone.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0036  Dapsone
MANUFACTURERS             Drug 1: Jacobus Pharmaceutical Company PO Box
                          5290 / 37 Cleveland Lane Princeton, NJ 08540
                          Contact: Dr David Jacobus (609) 921-7447
                          Contact: Dr Neil Lewis (609) 921-7447.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 2 mg/kg (maximum 100
                          mg/dose) once daily or 4 mg/kg (maximum 200
                          mg/dose) once weekly, for a minimum of 3
                          months
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral; 10 mg/5 ml syrup
                          and 25 and 100 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 3 months.
OTHER TREATMENT INFO.     END POINT: Hematologic and dermatologic
                          toxicity to dapsone.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Unacceptable
                          toxicity. 2. Patient noncompliance related to
                          failure to take study drug or keep scheduled
                          appointments. 3. At the request of parent or
                          guardian or at the discretion of ACTG, NIAID,
                          FDA, investigator, or pharmaceutical sponsor.
OTHER TREATMENT INFO.     MODIFICATION: Special criteria have been
                          determined for evaluation of hematologic,
                          hepatic, allergic, and neurologic toxicities.
                          Alternative explanations for clinical and
                          laboratory toxicities should be sought prior
                          to withholding study drug. If study drug is
                          discontinued for toxicities attributed to
                          other drugs, the study drug must be restarted
                          within 14 days (for daily dose) or 18 days
                          (for weekly dose), provided there is no
                          contraindication.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Jacobus Pharmaceutical
                          Company.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Child
MESH HEADING              Dapsone/*ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Drug Administration Schedule
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *PREVENTION & CONTROL
CAS REGISTRY NUMBER       80-08-0 (Dapsone)
LAST REVISION DATE        941207
ENTRY MONTH               9207
ALABAMA                   University of Alabama at Birmingham School of
                          Medicine 751 CHT / University Station
                          Birmingham, AL 35294 Contact: Michael Cooney
                          (205) 939-9552 Contact: beeper (205) 869-9524
                          OPEN 930203 ACTU: 5046.
CALIFORNIA                UCLA Medical Center / Pediatrics 10833 Le
                          Conte Avenue Los Angeles, CA 90024-1752
                          Contact: Leslie Spring (310) 206-6369 OPEN
                          930430 ACTU: 3601.
CALIFORNIA                Long Beach Memorial Medical Center /
                          Pediatrics 10833 Le Conte Avenue Los Angeles,
                          CA 90024-1752 Contact: Leslie Spring (310)
                          206-6369 OPEN 940513 ACTU: 3606.
CALIFORNIA                Los Angeles County USC Medical Center 1129
                          North State Street Los Angeles, CA 90033
                          Contact: Janice Ono (213) 226-3945 OPEN
                          931020 ACTU: 5048.
CALIFORNIA                University of CA San Diego Medical Center /
                          Pediatric 9500 Gilman Drive / Clinical
                          Sciences Bldg LaJolla, CA 92093-0672 Contact:
                          Candace McIvor (619) 534-7170 OPEN 920702
                          ACTU: 4601.
CALIFORNIA                Children's Hospital Oakland 747 Fifty Second
                          Street Oakland, CA 94609-1809 Contact: Jim
                          Riddel (510) 428-3000 X 282Contact: (510)
                          539-6311 X PagOPEN 930402 ACTU: 4504.
COLORADO                  University of Colorado Hlth Sciences Ctr /
                          Peds Infect Dis 1056 East 19Th Avenue B055
                          Denver, CO 80218-1088 Contact: Carol
                          Salbenblatt (303) 861-6751 OPEN 930408 ACTU:
                          7001.
DISTRICT OF COLUMBIA      Children's National Medical Center / Special
                          Immuno Svc Suite 2108 / 111 Michigan Avenue
                          NW Washington, DC 20010-2970 Contact: Sandra
                          Jones (202) 884-3682 OPEN 930601 ACTU: 7101.
DISTRICT OF COLUMBIA      Howard University Hospital 2041 Georgia
                          Avenue NW Washington, DC 20060 Contact: Dr
                          Helga Finke (202) 865-1248 OPEN 921106 ACTU:
                          5044.
FLORIDA                   Northeast Florida AIDS Program / Div of
                          Pediatric Inf Dis/Im 653-1 W 8th Street
                          Jacksonville, FL 32209 Contact: Michelle
                          Eagle (904) 549-3051 OPEN 940909 ACTU: 5051.
FLORIDA                   Univ of Miami School of Medicine / Pediatric
                          Imm Infect Dis 1800 NW Tenth Avenue Miami, FL
                          33136 Contact: Janet Gourley (305) 548-4446
                          OPEN 940524 ACTU: 4201.
GEORGIA                   Emory University Hospital 69 Butler Street SE
                          Atlanta, GA 30303 Contact: Judy Sarver (404)
                          616-6227 Contact: clinic (404) 616-4390
                          Contact: beeper (404) 899-5290 OPEN 921021
                          ACTU: 5030.
ILLINOIS                  University of Illinois at Chicago 840 S Wood
                          Street Chicago, IL 60612 Contact: Patricia
                          Naughton (312) 996-1778 OPEN 930727 ACTU:
                          5028.
ILLINOIS                  Chicago Children's Memorial Hospital /
                          Pediatric 2300 Childrens Plaza Box 20
                          Chicago, IL 60614-3394 Contact: Debbie Fonken
                          (312) 880-4757 OPEN 920702 ACTU: 4001.
ILLINOIS                  Cook County Hospital / Childrens Memorial
                          2300 Childrens Plaza Box #20 Chicago, IL
                          60614-3394 Contact: Debbie Fonken (312)
                          880-4757 OPEN 921027 ACTU: 4002.
ILLINOIS                  Wyler Children's Hospital 5841 South Maryland
                          Avenue Chicago, IL 60637-1470 Contact: Kim
                          Stieglitz (312) 702-6176 OPEN 940131 ACTU:
                          4003.
LOUISIANA                 Tulane University School of Medicine / Div of
                          Ped Infect Dis 1430 Tulane Avenue / PO Box
                          SL37 New Orleans, LA 70112-2699 Contact: Jane
                          Price (504) 585-7153 OPEN 920630 ACTU: 7201.
MASSACHUSETTS             Baystate Medical Center / Department of
                          Pediatrics 759 Chestnut Street / SHU-Main 3
                          Springfield, MA 01199 Contact: MaryPat Toye
                          (413) 784-5399 OPEN 920827 ACTU: 7302.
MASSACHUSETTS             University of Massachusetts Medical School /
                          Dept of Peds 55 Lake Avenue North Worcester,
                          MA 01655-0001 Contact: Joanne Shepard (508)
                          856-1692 OPEN 921022 ACTU: 7301.
MASSACHUSETTS             Children's Hospital 300 Longwood Avenue /
                          Carnegie 3 Boston, MA 02115 Contact: Robert
                          Bishop (617) 735-8198 OPEN 920630 ACTU: 2901.
MASSACHUSETTS             Boston City Hospital / Ped Infect Dis /
                          Finland Lab 774 Albany Street / Finland Lab
                          Room 301 Boston, MA 02118 Contact: Anne Marie
                          Reagan (617) 534-5813 OPEN 920910 ACTU: 2903.
MICHIGAN                  Children's Hospital of Michigan 3901 Beaubien
                          Boulevard Detroit, MI 48201 Contact: Charnell
                          Cromer (313) 745-5565 OPEN 930318 ACTU: 5041.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          930727 ACTU: 3201.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 OPEN 930624 ACTU:
                          4701.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 921215 ACTU: 2801.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          Ninth Street Newark, NJ 07107-2198 Contact:
                          George Donavan McSherry (201) 268-8273 OPEN
                          930420 ACTU: 2803.
NEW JERSEY                Robert Wood Johnson University Hospital /
                          UMDNJ One Robert Wood Johnson Place CN19 New
                          Brunswick, NJ 08903-0019 Contact: Ida Kechula
                          (908) 937-7894 OPEN 930923 ACTU: 5032.
NEW YORK                  Beth Israel Medical Center / Pediatrics First
                          Avenue at 16th Street Dazian Pavilion Tenth
                          Floor New York, NY 10003 Contact: Ann Marshak
                          (212) 420-4432 OPEN 920818 ACTU: 4302.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue / Pediatric
                          New York, NY 10016 Contact: Nagamah Deygoo
                          (212) 263-6426 OPEN 930128 ACTU: 4401.
NEW YORK                  Memorial Hospital / Memorial Sloan-Kettering
                          Cancer Center 1275 York Avenue New York, NY
                          10021 Contact: Gloria Gilbert (212) 639-7169
                          OPEN 930727 ACTU: 2202.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          920818 ACTU: 1801.
NEW YORK                  Mount Sinai School of Medicine / Pediatrics
                          One Gustave L Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-8903
                          Contact: (212) 241-7856 OPEN 940301 ACTU:
                          4301.
NEW YORK                  Incarnation Children's Ctr / c/o Columbia
                          Presb Med Ctr 142 Audubon Avenue New York, NY
                          10032 Contact: Pam Clark (212) 928-2228 OPEN
                          921222 ACTU: 4103.
NEW YORK                  The Columbia Presbyterian Medical Hosp
                          (Pediatric) 622 West 168th St Room 1161 New
                          York, NY 10032-3796 Contact: Kathy A Shea
                          (212) 305-7222 OPEN 921222 ACTU: 4101.
NEW YORK                  Harlem Hospital 506 Lenox Avenue New York, NY
                          10037 Contact: Rick Urbano (212) 939-4040
                          Contact: (212) 939-4045 OPEN 920714 ACTU:
                          5006.
NEW YORK                  Albert Einstein College of Medicine /
                          Pediatrics 1300 Morris Park Avenue / Mazer
                          Room 219 Bronx, NY 10461 Contact: Sarah
                          Patterson (718) 430-2940 Contact: Clin (718)
                          918-5462 OPEN 920902 ACTU: 4901.
NEW YORK                  North Shore University Hospital / Pediatric
                          Immunology 350 Community Drive Manhasset, NY
                          11030 Contact: Cathy Macco (516) 773-7676
                          OPEN 930518 ACTU: 5010.
NEW YORK                  Schneider Children's Hospital / Long Island
                          Jewish Med Ctr 270-05 76th Avenue Room 235 /
                          Div of Allergy and Immunology New Hyde Park,
                          NY 11042 Contact: Debby Hickey (718) 470-3300
                          OPEN 920706 ACTU: 5001.
NEW YORK                  King's County Hospital Center / SUNY HSCB 450
                          Clarkson Avenue Brooklyn, NY 11203 Contact:
                          Helen Bergin (718) 245-3342 Contact: (718)
                          245-3341 Contact: (718) 245-4485 OPEN 930216
                          ACTU: 5035.
NEW YORK                  SUNY Health Science Center at Stony Brook HSC
                          T 15 080 Stony Brook, NY 11794-8111 Contact:
                          Peggy Melendez (516) 444-1313 Contact: (516)
                          444-7692 Contact: beeper (516) 282-8808
                          Contact: Jeannie Conner (516) 444-2724 OPEN
                          920729 ACTU: 5040.
NEW YORK                  SUNY Health Science Center at Syracuse 750
                          East Adams Street Syracuse, NY 13210 Contact:
                          Kathie Shea-Contello (315) 464-6331 OPEN
                          921215 ACTU: 5039.
NEW YORK                  University of Rochester Medical Center Box
                          689 / 601 Elmwood Avenue Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 921009 ACTU: 1101.
OHIO                      Childrens Hospital of Cincinnati Eden and
                          Bethesda Avenue Cincinnati, OH 45267-0405
                          Contact: Jill Leonard (513) 558-6977 OPEN
                          931021 ACTU: 2404.
OTHER                     San Juan City Hospital / Puerto Rico Medical
                          Center Department of Pediatrics Third Floor
                          Hematology Rio Piedras, PR 00927 Contact:
                          Esther Rosa (809) 764-3083 Contact: (809)
                          274-0904 OPEN 930216 ACTU: 5031.
PENNSYLVANIA              Children's Hospital of Philadelphia 34th
                          Street & Civic Center Blvd Philadelphia, PA
                          19104-4399 Contact: Dr Deborah Schaible (215)
                          590-2097 Contact: Hospital Information (215)
                          590-1000 OPEN 921029 ACTU: 6701.
PENNSYLVANIA              Saint Christopher's Hospital for Children /
                          Sect Imm & Rheum Erie Avenue at Front Street
                          Philadelphia, PA 19134-1095 Contact: Carole
                          Treston (215) 427-5284 Contact: FAX (215)
                          427-5555 OPEN 930805 ACTU: 6704.
SOUTH CAROLINA            Medical University of South Carolina Clinical
                          Science Building / 171 Ashley Avenue
                          Charleston, SC 29425-3312 Contact: Genny
                          Connelly (803) 792-2385 OPEN 921112 ACTU:
                          5037.
 
60
UNIQUE IDENTIFIER         NIH/00239
PROTOCOL ID NUMBERS       NIAID ACTG 177
PROTOCOL TITLE            Prophylaxis Against Mycobacterium
                          Tuberculosis (MTb) in Patients Who Are
                          Infected With the Human Immunodeficiency
                          Virus (HIV) and Suspected or Confirmed Latent
                          MTb Infection.
VERSION NUMBER & DATE     4 (940630)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Chaisson R
GENERAL DESCRIPTION       PURPOSE: To evaluate and compare the safety
                          and effectiveness of a one-year course of
                          isoniazid (INH) versus a two-month course of
                          rifampin plus pyrazinamide for the prevention
                          of reactivation tuberculosis in individuals
                          infected with both HIV and latent (inactive)
                          Mycobacterium tuberculosis.
GENERAL DESCRIPTION       RATIONALE: Current guidelines from the
                          American Thoracic Society and the Centers for
                          Disease Control recommend 6 to 12 months of
                          INH for PPD (purified protein
                          derivative)-positive individuals. Although
                          the effectiveness of this treatment is not
                          known for HIV-infected individuals, several
                          studies using INH to prevent tuberculosis in
                          presumably normal hosts have shown 60 to 80
                          percent effectiveness. Problems with this
                          treatment include compliance, adverse
                          reaction, and the possibility of not
                          preventing disease due to tuberculosis
                          organisms being resistant to INH. A two-month
                          preventive treatment plan should help in
                          increasing compliance. In addition, the use
                          of two drugs (rifampin / pyrazinamide) may
                          help overcome problems with drug resistance.
                          If this study shows equal or greater
                          effectiveness of the two month rifampin /
                          pyrazinamide treatment, it could alter the
                          approach to tuberculosis prevention for both
                          HIV-positive and HIV-negative individuals.
GENERAL DESCRIPTION       METHODOLOGY: Patients are chosen by a random
                          selection process to either the INH or the
                          rifampin / pyrazinamide arm of the dose.
                          Patients on the INH arm receive 300 mg INH
                          plus 50 mg vitamin B6 (pyridoxine) per day
                          for 12 months. Patients on the other arm
                          receive rifampin (450 - 600 mg/day) plus
                          pyrazinamide (500 - 3000 mg/day) for 60 days.
                          Dosage of rifampin and pyrazinamide depends
                          on weight of patient.
PROTOCOL PHASE            Unspecified
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Tuberculosis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Written documentation of
                          positive antibody to HIV by federally
                          licensed ELISA, confirmed by another method,
                          such as Western blot, RIA, HIV culture. (If a
                          prior diagnosis of AIDS has been established
                          by CDC criteria, confirmatory test is not
                          required.) 2. Positive PPD skin test (defined
                          as = or > 5 mm induration to 5-TU of PPD
                          using Mantoux method, to be read between 48
                          and 72 hours after application) but without
                          evidence of active clinical tuberculosis: OR
                          Documented history of a positive PPD skin
                          test without subsequent treatment or
                          prophylaxis with > 2 months of any
                          antimycobacterial medication. (Note: While
                          the optimal time for reading the PPD is
                          between 48 and 72 hours, positive reactions
                          beyond 72 hours are acceptable.)
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Prospective; Randomized; Comparative; Dose
                          Comparison; Multicenter; Open Label; 2-Arm
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy,
                          Combination and single drug therapy, Drug
                          efficacy, Drug safety, Drug prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 2000 patients. This study
                          is part of a larger collaborative CPCRA /
                          ACTG study; total required is 2000 patients.
                          Analysis is based on total 2000; ACTG
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 24
                          months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 388/2000 (941207).
PROTOCOL DETAILS          STUDY DURATION: 72 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 73 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Current or
                          documented history of positive PPD skin test.
                          3. Life expectancy of at least 6 months or,
                          in the physician's opinion, patient has a
                          reasonable chance of survival to end of
                          study. Allowed: Participation in other
                          clinical trials as long as there is no
                          potential activity of other study drugs
                          against Mycobacterium tuberculosis (MTb),
                          additive toxicities between study agents, or
                          known possible drug interactions between
                          study drugs. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. ULN = upper limit of
                          normal.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophil count > 750
                          cells/mm3. Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study. Not pregnant. Negative
                          pregnancy test within 30 days of study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Antiretroviral treatment. Pneumocystis
                          carinii pneumonia prophylaxis. Treatment for
                          acute opportunistic infection.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients may not
                          have the following prior conditions: History
                          of sensitivity / intolerance to any study
                          medication. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Positive pregnancy
                          test within 30 days of study entry. Pregnant.
                          No abstinence or no agreement to use
                          effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Unwilling or unable to comply
                          with the follow-up requirements of the
                          protocol.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: More than 2
                          months of continuous treatment, after
                          documentation of a positive PPD skin test,
                          with agents that have known or potential
                          antituberculous activity OR any
                          antimycobacterial medication for > 1 month.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Treatment
                          with quinolones, fluoroquinolones,
                          aminoglycosides, or other agents that have
                          activity against Mycobacterium tuberculosis.
                          Excluded as ongoing (i.e., continuous,
                          chronic and/or recurring) treatment:
                          Aminoglycosides such as amikacin.
                          Aminosalicylic acid salts (PAS). Capreomycin.
                          Clofazimine. Cycloserine. Ethambutol.
                          Ethionamide. Isoniazid (INH) if randomized to
                          rifampin/pyrazinamide arm of study.
                          Kanamycin. Pyrazinamide if randomized to INH
                          arm of study. Quinolones and fluoroquinolones
                          including but not limited to rifabutin,
                          rifampin (if randomized to INH arm of study),
                          ciprofloxacin, levofloxacin, ofloxacin,
                          streptomycin, thiacetazone.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions or symptoms are excluded: 1.
                          Current active clinical tuberculosis,
                          confirmed or suspected. 2. History of
                          sensitivity / intolerance to any study
                          medication. 3. Evidence of peripheral
                          neuropathy, i.e., signs or symptoms of
                          paresis, paresthesias, neuromotor
                          abnormalities, or neurosensory deficits of
                          grade 3 or worse. 4. Unwilling or unable to
                          have current therapy and/or concomitant
                          medication changed to avoid serious
                          interaction with study medication. 5. Acute
                          hepatitis. 6. Unable to comply with the
                          follow-up requirements of the protocol.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0109  Rifampin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0125  Pyridoxine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0124  Pyrazinamide
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0123  Isoniazid
MANUFACTURERS             Drug 1: Marion Merrell Dow Medical
                          Information / PO Box 9627 Kansas City, MO
                          64134-0627 Contact: Medical Information (800)
                          633-1610.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
MANUFACTURERS             Drug 4: Lannett Company Incorporated 9000
                          State Road Philadelphia, PA 19136 Contact:
                          Vlad Mikijanic (215) 333-9000.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 450 - 600 mg/day for
                          60 days. Drug 2: 50 mg/day for 12 months.
                          Drug 3: 500 - 3000 mg/day for 60 days. Drug
                          4: 300 mg daily for 12 months
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 450 - 600 mg. Drug 2:
                          50 mg. Drug 3: 500 - 3000 mg. Drug 4: 300 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 150 or 300 mg
                          capsules. Drug 2: Oral, 50 mg tablets. Drug
                          3: Oral, 500 mg scored tablets. Drug 4: Oral,
                          300 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: Sixty days (rifampin +
                          pyrazinamide) or 12 months (isoniazid +
                          pyridoxine).
OTHER TREATMENT INFO.     END POINT: Primary end point: Time to
                          development of confirmed active tuberculosis.
                          Secondary end point: Combined end points of
                          death and confirmed or probable clinical
                          tuberculosis, toxicity from treatment, and
                          laboratory findings.
OTHER TREATMENT INFO.     DISCONTINUE: Study drugs will be discontinued
                          for the following: 1. Development of any
                          confirmed or probable active pulmonary or
                          extrapulmonary tuberculosis. 2. Development
                          of severe clinical hepatitis due to study
                          drug. 3. Development of Mycobacterium avium
                          infection requiring continuous, chronic, or
                          recurrent treatment with agents active in the
                          treatment of tuberculosis, at the
                          investigator's discretion. 4. Persistent or
                          recurring severe study drug toxicity despite
                          temporary drug discontinuation.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 hepatic toxicity:
                          withhold study drug until toxicity resolves
                          to baseline. For grade 4 hepatic toxicity:
                          discontinue study drug. For grade 3 or 4
                          peripheral neuropathy: withhold study drug
                          until toxicity resolves to grade 2 or lower.
                          Restart study drug at investigator's
                          discretion. For grade 2 rash: withhold study
                          drug at the discretion of the investigator.
                          For grade 3 or 4 rash: discontinue study
                          drug. For grade 2 nausea or vomiting
                          toxicity: withhold study drug until symptoms
                          subside to grade 1 or lower. For grade 2
                          nausea or vomiting toxicity with laboratory
                          evidence of transaminitis: withhold study
                          drug and monitor symptoms and laboratory
                          data. If signs and symptoms appear to be due
                          to drug-induced hepatitis, discontinue study
                          drug. For recurrent grade 2 nausea and
                          vomiting: discontinue study drug. For grade 3
                          or 4 nausea or vomiting toxicity: withhold
                          study drug until symptoms subside or resolve
                          to baseline. For grade 3 or 4 nausea/vomiting
                          related to drug-induced hepatitis,
                          discontinue study drug permanently. For grade
                          2 or higher fever: withhold study drug until
                          etiology of fever has been determined. If
                          isoniazid (INH) is interrupted due to
                          toxicity or other reasons, every effort
                          should be made to have patient on the INH
                          receive at least 6 reasonably continuous
                          months of study drug. Multiple interruptions
                          are permissible, and patients may receive INH
                          beyond the first 12 months after
                          randomization if this is required to complete
                          6 reasonably continuous months of study drug.
                          If rifampin / pyrazinamide treatment is
                          interrupted due to toxicity or other reasons,
                          every effort should be made to have patients
                          receive 60 days of study drug. Multiple
                          interruptions are permissible and patients
                          may receive rifampin / pyrazinamide beyond
                          the first 2 months after randomization if
                          necessary.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Lederle Laboratories, Marion
                          Merrell Dow Research Institute.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antitubercular Agents/ADMINISTRATION & DOSAGE/
                          *THERAPEUTIC USE
MESH HEADING              Comparative Study
MESH HEADING              Drug Evaluation
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Isoniazid/ADMINISTRATION & DOSAGE/THERAPEUTIC
                          USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Multicenter Studies
MESH HEADING              Mycobacterium tuberculosis/DRUG EFFECTS
MESH HEADING              Opportunistic Infections/COMPLICATIONS/
                          PREVENTION & CONTROL
MESH HEADING              Pyrazinamide/ADMINISTRATION & DOSAGE/
                          THERAPEUTIC USE
MESH HEADING              Pyridoxine/ADMINISTRATION & DOSAGE/
                          THERAPEUTIC USE
MESH HEADING              Rifampin/ADMINISTRATION & DOSAGE/THERAPEUTIC
                          USE
MESH HEADING              Tuberculosis/COMPLICATIONS/*PREVENTION &
                          CONTROL
CAS REGISTRY NUMBER       0 (Antitubercular Agents)
CAS REGISTRY NUMBER       13292-46-1 (Rifampin)
CAS REGISTRY NUMBER       54-85-3 (Isoniazid)
CAS REGISTRY NUMBER       65-23-6 (Pyridoxine)
CAS REGISTRY NUMBER       98-96-4 (Pyrazinamide)
LAST REVISION DATE        941207
ENTRY MONTH               9112
ALABAMA                   University of Alabama at Birmingham 908 20th
                          Street S / 1917 Research Clinic Room 135
                          Birmingham, AL 35294-2041 Contact: Susan
                          Duncan (205) 934-3690 OPEN 940711 ACTU: 5801.
CALIFORNIA                Children's Hospital of Los Angeles /
                          Children's AIDS Center 4650 Sunset Blvd /
                          Mail Stop #54 Los Angeles, CA 90027 Contact:
                          Antonieta Sosa (213) 669-2180 OPEN 941110
                          ACTU: 9916.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          930427 ACTU: 1201.
CALIFORNIA                Harbor General / REI Lab / UCLA 1124 West
                          Carson Street Torrance, CA 90502 Contact:
                          Sally Kruger (310) 222-3848 Contact: Rick
                          Johnson OPEN 911031 ACTU: 0603.
CALIFORNIA                Olive View Medical Center / Department of
                          Medicine 14445 Olive View Drive / 2B182 Olive
                          View Medical Center Sylmar, CA 91342 Contact:
                          Betsy Manchester (818) 364-3205 OPEN 940513
                          ACTU: 0602.
CALIFORNIA                AIDS Community Research Consortium 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harris (415) 364-5653 OPEN
                          920902 ACTU: 0505.
CALIFORNIA                Santa Clara Valley Med Ctr / ACRC 1048 El
                          Camino Real / Suite A Redwood City, CA 94063
                          Contact: Deborah Harriss (415) 364-5653 OPEN
                          920902 ACTU: 0506.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 840OPEN 920911 ACTU: 0801.
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 920914 ACTU: 0808.
CALIFORNIA                Kaiser Permanente Medical Group / Stanford
                          University 2590 Geary Boulevard San
                          Francisco, CA 94115 Contact: Gretchen Van
                          Raalte (415) 202-3482 OPEN 911031 ACTU: 0502.
CALIFORNIA                Stanford University School of Medicine 300
                          Pasteur Drive Stanford, CA 94305 Contact:
                          Virginia Tallman (415) 723-2804 Contact: Dr
                          Rami Ramachandran (415) 723-6231 OPEN 920702
                          ACTU: 0501.
CONNECTICUT               Yale University School of Medicine / Sect of
                          Infectious Dis 135 College Street New Haven,
                          CT 06510-2483 Contact: Laurie Andrews (203)
                          737-4040 OPEN 920824 ACTU: 6401.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Kober
                          Cogan 110 / 3800 Reservoir Road NW
                          Washington, DC 20007-2197 Contact: Karen
                          Gammon (202) 687-1079 OPEN 921224 ACTU: 5701.
DISTRICT OF COLUMBIA      HIV Center - DC General Hospital / Georgetown
                          Univ Med Ctr Kober-Cogan 110 / 3800 Reservoir
                          Road NW Washington, DC 20007-2197 Contact:
                          Karen Gammon (202) 687-1079 Contact: Fax
                          (202) 687-6476 OPEN 930126 ACTU: 5703.
DISTRICT OF COLUMBIA      Whitman-Walker Clinic / Georgetown Univ
                          Medical Center Kober-Cogan 110 / 3800
                          Reservoir Road NW Washington, DC 20007-2197
                          Contact: Karen Gammon (202) 687-1079 Contact:
                          Fax (202) 687-6476 OPEN 931008 ACTU: 5702.
DISTRICT OF COLUMBIA      Howard U Coll of Med / AIDS Minority
                          Infrastructure Program 2112 Georgia Avenue NW
                          Washington, DC 20059 Contact: Victoria Holly
                          -Trimmer (202) 806-4700 Contact: (202)
                          806-4755 OPEN 921215 ACTU: 5301.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue / Elliot Building First Floor
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 Contact: (305) 547-3838 OPEN 920506
                          ACTU: 0901.
HAWAII                    Hawaii Aids Clinical Trails Unit Leahi
                          Hospital / Young Bldg / 3675 Kilauea Avenue /
                          6th Flr Honolulu, HI 96816 Contact: Debra M
                          Ogata Arakaki (808) 737-2751 OPEN 921215
                          ACTU: 5201.
ILLINOIS                  Children's Memorial Hospital Family Clinic
                          303 East Superior Passavant Pavilion Room 823
                          Chicago, IL 60611 Contact: Baiba L Berzins RN
                          (312) 908-9636 OPEN 911107 ACTU: 2704.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 911031 ACTU: 2701.
ILLINOIS                  Louis A Weiss Memorial Hospital /
                          Northwestern Univ Med Schl 303 East Superior
                          Street Passavant 823 Chicago, IL 60611
                          Contact: Baiba Berzins (312) 908-9636 OPEN
                          941017 ACTU: 2708.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 920805 ACTU: 2702.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 940721 ACTU: 2601.
MASSACHUSETTS             Bay State Medical Center 759 Chestnut Street
                          Springfield, MA 01199 Contact: Deborah
                          Naglieri-Prescod (413) 784-3046 OPEN 920106
                          ACTU: 3002.
MASSACHUSETTS             New England Deaconess Hospital 185 Pilgrim
                          Road Boston, MA 02215 Contact: Helen Fitch
                          (617) 735-0785 OPEN 941020 ACTU: 0103.
MARYLAND                  Johns Hopkins University / Infectious
                          Diseases 1830 East Monument Street Room 8071
                          Baltimore, MD 21205 Contact: Becky Becker
                          (410) 955-2898 OPEN 911210 ACTU: 0201.
MARYLAND                  State of Maryland Div of Corrections c/o
                          Johns Hopkins Hosp 1830 East Monument Street
                          / Room 8071 Baltimore, MD 21205 Contact:
                          Becky Becker (410) 955-2898 OPEN 920304 ACTU:
                          0202.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 920313 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 920313
                          ACTU: 2102.
NORTH CAROLINA            Moses H Cone Memorial Hospital / University
                          North Carolina 1200 North Elm Street
                          Greensboro, NC 27401 Contact: Pam Mentley
                          (910) 574-7888 OPEN 920228 ACTU: 3203.
NORTH CAROLINA            University of North Carolina at Chapel Hill
                          516 Burnett-Womack Building / CB #7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-6712 Contact: (919) 966-7883 OPEN
                          911126 ACTU: 3201.
NORTH CAROLINA            Wake County Department of Health Hosp South
                          Room 0207 Box 3284 Durham, NC 27710 Contact:
                          Kelley Rayle (919) 250-1035 OPEN 930607 ACTU:
                          3206.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Frances Tennant (402) 559-5750 OPEN
                          930720 ACTU: 1505.
NEW JERSEY                Children's Hospital of New Jersey 15 South
                          9th Street / CHAP Program 5 East Newark, NJ
                          07107 Contact: George Donovan Mcsherry (201)
                          268-8273 OPEN 930414 ACTU: 2801.
NEW JERSEY                Univ of Med & Dentistry of NJ / Univ Hospital
                          15 South Ninth Street Newark, NJ 07107-2198
                          Contact: George Donavan Mcsherry (201)
                          268-8273 OPEN 911202 ACTU: 2802.
NEW YORK                  Beth Israel Medical Center ( Mount Sinai )
                          16th Street at 1st Ave / 10Th Floor Dazian
                          Pavilion New York, NY 10003 Contact: Ann
                          Marshak (212) 420-4432 OPEN 911202 ACTU:
                          1802.
NEW YORK                  Bellevue Hospital / New York University
                          Medical Center 550 First Avenue New York, NY
                          10016 Contact: Mary Ann Kiernan (212)
                          263-6565 OPEN 911031 ACTU: 0401.
NEW YORK                  Saint Luke's Roosevelt Hospital 432 West 58th
                          Street Antenucchi Building Lobby Level ANT 1
                          New York, NY 10019 Contact: Julie Linksman
                          Rivera (212) 523-6743 CLOSED 930317 ACTU:
                          3401.
NEW YORK                  St Clare's Hospital and Health Center 415
                          West 51st Street New York, NY 10019 Contact:
                          Phyllis Ristau (212) 459-8449 OPEN 920729
                          ACTU: 2204.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          911031 ACTU: 2201.
NEW YORK                  Memorial Hospital / Memorial Sloan-Kettering
                          Cancer Center 1275 York Avenue New York, NY
                          10021 Contact: Glennon Stutterer (212)
                          639-7161 OPEN 921221.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          911202 ACTU: 1801.
NEW YORK                  Columbia Presbyterian Medical Center 622 West
                          168 Street / Harkness Pavilion 5 Room 516 New
                          York, NY 10032-3784 Contact: Mykyelle Wade
                          (212) 305-8507 OPEN 940311 ACTU: 7501.
NEW YORK                  Montefiore Drug Treatment Center 418
                          Forchheimer-ID / 1300 Morris Avenue Bronx, NY
                          10461 Contact: Nahla Mohamed (718) 430-3639
                          Contact: (718) 920-5344 OPEN 911113 ACTU:
                          1905.
NEW YORK                  North Central Bronx Hospital / Montefiore
                          Family Health Cntr 418 Forchheimer-ID/1300
                          Morris Park Ave Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 911113 ACTU: 1906.
NEW YORK                  North Central Bronx Hospital / Samaritan
                          Village Inc 418 Forchheimer ID / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 911113 ACTU: 1907.
NEW YORK                  Comprehensive Health Care Center 418
                          Forchheimer-ID / 1300 Morris Park Ave Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 940418
                          ACTU: 1908.
NEW YORK                  Albert Einstein College of Medicine 418
                          Forcheimer / 1300 Morris Park Avenue Bronx,
                          NY 10461 Contact: Nahla Mohamed (718)
                          430-3659 Contact: (718) 920-5344 OPEN 911113
                          ACTU: 1904.
NEW YORK                  Montefiore Medical Center / Albert Einstein
                          College of Med 418 Forchheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 911113 ACTU: 1903.
NEW YORK                  Bronx Municipal Hospital / Albert Einstein
                          College of Med Forchheimer 418 / 1300 Morris
                          Park Avenue Bronx, NY 10461 Contact: Nahla
                          Mohamed (718) 430-3659 Contact: (718)
                          920-5344 OPEN 911107 ACTU: 1901.
NEW YORK                  Jack Weiler Hospital / Albert Einstein
                          College of Med 418 Fochheimer-ID / 1300
                          Morris Park Avenue Bronx, NY 10461 Contact:
                          Nahla Mohamed (718) 430-3659 OPEN 911031
                          ACTU: 1902.
NEW YORK                  Montefiore Medical Center / Adolescent AIDS
                          Program 111 East 210th Street / NW674 Bronx,
                          NY 10467 Contact: Dina Monte (718) 882-0023
                          OPEN 921224 ACTU: 4903.
NEW YORK                  North Shore University Hospital 300 Community
                          Drive Manhasset, NY 11030 Contact: Patricia
                          Gemma (516) 562-1528 OPEN 930329 ACTU: 2203.
NEW YORK                  SUNY Health Sciences Center at Brooklyn ACTU
                          Box 77 / 450 Clarkson Avenue Brooklyn, NY
                          11203-2098 Contact: Donald Smith (718)
                          270-3372 Contact: (718) 270-3370 OPEN 920603
                          ACTU: 5901.
NEW YORK                  City Hospital at Elmhurst / Mt Sinai 79-01
                          Broadway Room D1-29 Elmhurst, NY 11373
                          Contact: Dinah Reitman (718) 334-3963 OPEN
                          920310 ACTU: 1803.
NEW YORK                  Nassau County Medical Center 2201 Hempstead
                          Turnpike East Meadow, NY 11554 Contact: Ann M
                          Gardner (516) 542-5707 Contact: (516)
                          542-5414 OPEN 911031 ACTU: 3302.
NEW YORK                  SUNY at Stony Brook Health Sciences Center T
                          15 080 Stony Brook, NY 11794-8153 Contact:
                          Ruth Ann Burk (516) 444-1658 Contact: Dr Roy
                          Steigbigel (516) 444-1660 Contact: Dr
                          Benjamin Luft (516) 444-1660 OPEN 911105
                          ACTU: 3301.
NEW YORK                  Adirondack Medical Center at Saranac Lake 47
                          New Scotland Avenue Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930819 ACTU: 7403.
NEW YORK                  Mid-Hudson Care Center / Albany Med College /
                          Div Med Oncol 47 New Scotland Avenue / Div
                          Med Oncology A52 Albany, NY 12208-6752
                          Contact: Patricia Amsler (518) 262-6759 OPEN
                          930819 ACTU: 7402.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 930727 ACTU: 7401.
NEW YORK                  SUNY Health Science Center / Dept of Medicine
                          750 East Adams Street / Rm 1254-WH Syracuse,
                          NY 13210 Contact: Linda Brasington (315)
                          464-5533 OPEN 920122 ACTU: 1103.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          920805 ACTU: 1102.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 911031
                          ACTU: 2301.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 921009 ACTU: 2501.
OHIO                      Metrohealth Medical Center / Case Western
                          Reserve Univ 2500 MetroHealth Drive
                          Cleveland, OH 44109-1998 Contact: Nancy
                          Frantz (216) 459-5136 OPEN 930603 ACTU: 2503.
OHIO                      University of Cincinnati School of Medicine
                          Eden and Bethesda Avenue / AIDS Clinical
                          Trials Cincinnati, OH 45267-0405 Contact:
                          Jill Leonard (513) 558-6977 OPEN 930301 ACTU:
                          2401.
OTHER                     University of Puerto Rico / Schl of Med / Inf
                          Dis Sec / ACTU G P O Box 365067 San Juan, PR
                          00936-5067 Contact: Maritza Cruz-Ortiz (809)
                          767-9192 Contact: (809) 767-9193 OPEN 930618
                          ACTU: 5401.
PENNSYLVANIA              University of Pennsylvania / Div of
                          Infectious Diseases 549 Johnson Pavillion /
                          6073 / 36th and Hamilton Walk Philadelphia,
                          PA 19104-6073 Contact: Debora Dunbar (215)
                          349-8092 OPEN 920603 ACTU: 6201.
PENNSYLVANIA              University of Pennsylvania / Girard Medical
                          Center 549 Johnson Pavillion/6073 / 36th and
                          Hamilton Walk Philadelphia, PA 19104-6073
                          Contact: Debora Dunbar (215) 349-8092 OPEN
                          921113 ACTU: 6203.
PENNSYLVANIA              Thomas Jefferson Unversity 1015 Chestnut
                          Street Philadelphia, PA 19107 Contact: Lyle
                          Jew (215) 955-7785 OPEN 920721 ACTU: 6202.
SOUTH CAROLINA            Medical University of SC / Infect Diseases
                          Division 807 CSB 171 Ashley Avenue
                          Charleston, SC 29425 Contact: Denise Taylor
                          (803) 782-6174 OPEN 921215 ACTU: 3205.
 
61
UNIQUE IDENTIFIER         NIH/00403
PROTOCOL ID NUMBERS       NIAID ACTG 149
PROTOCOL TITLE            Phase II Study of G-CSF Plus ABVD (Adriamycin
                          / Bleomycin / Vinblastine / Dacarbazine) in
                          the Treatment of HIV-Associated Hodgkin's
                          Disease.
VERSION NUMBER & DATE     3 (940419) Final
TRIAL CATEGORY            AIDS-Related Malignancies
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Levine A
GENERAL DESCRIPTION       PURPOSE: Primary: To assess the toxicity of
                          chemotherapy with ABVD (doxorubicin /
                          bleomycin / vinblastine / dacarbazine) when
                          given with granulocyte colony-stimulating
                          factor (G-CSF) in patients with underlying
                          HIV infection and Hodgkin's disease; to
                          observe the efficacy of ABVD and G-CSF in
                          reducing tumor burden in HIV-infected
                          patients with Hodgkin's disease. Secondary:
                          To determine the durability of tumor response
                          to ABVD plus G-CSF over the 2-year study
                          period; to observe the incidence of bacterial
                          and opportunistic infections in HIV-infected
                          patients with Hodgkin's disease receiving
                          this regimen; to document quality of life of
                          patients receiving this regimen.
GENERAL DESCRIPTION       RATIONALE: Addition of granulocyte
                          colony-stimulating factor may prevent
                          neutropenia caused by chemotherapy, allowing
                          more timely administration of chemotherapy
                          and improved response.
GENERAL DESCRIPTION       METHODOLOGY: Study drugs are administered in
                          28-day cycles to twenty-seven HIV-infected
                          patients with Hodgkin's disease. ABVD
                          (doxorubicin / bleomycin / vinblastine /
                          dacarbazine) is administered on days 1 and 15
                          of each cycle, and granulocyte
                          colony-stimulating factor (G-CSF) is given on
                          days 2 through 14 and 16 through 28 of each
                          cycle. All patients receive four cycles of
                          treatment and are then restaged. Patients
                          with a complete response (CR) following the
                          initial four cycles receive two additional
                          cycles of ABVD / G-CSF. Patients with a
                          partial response following the initial four
                          cycles receive two additional cycles of ABVD
                          / G-CSF and are again restaged; those who
                          have achieved a CR at that point then receive
                          two more cycles, while those without CR
                          discontinue study therapy. Patients with
                          disease progression following the initial
                          four cycles of therapy discontinue treatment
                          on the study. Concomitant PCP prophylaxis is
                          administered.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941207)
DISEASE STUDIED           Hodgkin's Disease.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA, HIV culture, or p24 antigen capture
                          assay, or prior diagnosis of AIDS by 1987 CDC
                          definition documented by medical records. 2.
                          Pathologic diagnosis of measurable Hodgkin's
                          disease (any stage) previously untreated by
                          chemotherapy or radiotherapy.
ELIGIBILITY               ASYM / OTHER. AIDS / OTHER. ARC / OTHER.
OTHER PROTOCOL NUMBERS    BB IND 4220
STUDY DESIGN              Multicenter; Open Label; Nonrandomized
PROTOCOL DETAILS          STUDY INTENT: Combination drug therapy, Drug
                          efficacy, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 27 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum 4
                          months.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 15/27 (941207).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 13 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection or
                          diagnosis of AIDS. 2. Hodgkin's disease. 3.
                          Consent of parent or guardian and have care
                          directly supervised by a pediatric oncologist
                          if under 18 years of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   GRANULOCYTES: > 1000 cells/mm3. (No
                          hematologic criteria applicable if bone
                          marrow involvement with tumor).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3. (No
                          hematologic criteria applicable if bone
                          marrow involvement with tumor).
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: LVEF > 50 (in patients who undergo
                          MUGA scan).
PATIENT AGE               AGE: 12 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Cranial
                          irradiation (2400 rads) for patients with CNS
                          involvement.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Maintenance
                          therapy for opportunistic infections.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: PCP
                          prophylaxis consisting of Bactrim,
                          aerosolized pentamidine, or dapsone.
                          Recommended: Antiemetic therapy within 30
                          minutes of chemotherapy. Allowed: 1.
                          Antiretroviral medication after two cycles of
                          chemotherapy, provided the patient has not
                          experienced grade 3 neutropenia while on
                          chemotherapy or on previous antiretroviral
                          therapy. 2. Acetaminophen and/or nonsteroidal
                          anti-inflammatory agents. 3. Bone
                          marrow-suppressive agents, such as
                          ganciclovir, Fansidar, Bactrim, and dapsone.
                          4. Maintenance therapy for chronic
                          opportunistic infection.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 11 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control /
                          contraception during the study.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Prior radiotherapy
                          for Hodgkin's disease.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          chemotherapy for Hodgkin's disease. 2.
                          Antiretroviral therapy within 2 weeks prior
                          to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Second primary cancer other than Kaposi's
                          sarcoma that does not require systemic
                          therapy, nonmelanomatous skin cancer, Bowen's
                          disease, or carcinoma in situ of the cervix.
                          2. Acute, active bacterial or opportunistic
                          infection requiring ongoing therapy if such
                          therapy has been initiated within the past 2
                          weeks. 3. Known hypersensitivity (e.g.,
                          anaphylactoid reaction, brochospasm) to E.
                          coli-derived proteins.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Not accessible for scheduled
                          treatment or follow-up visits.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0047  Doxorubicin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0045  Bleomycin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0134  Vinblastine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0135  Dacarbazine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0086  Granulocyte
                          colony-stimulating factor
TRADE NAME OF SUBSTANCE   Drug 1 Adriamycin
TRADE NAME OF SUBSTANCE   Drug 2 Blenoxane
TRADE NAME OF SUBSTANCE   Drug 3 Velban
TRADE NAME OF SUBSTANCE   Drug 4 DTIC
TRADE NAME OF SUBSTANCE   Drug 5 Neupogen
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 5: Amgen Incorporated 1840 DeHavilland
                          Drive Thousand Oaks, CA 91320-1789 Contact:
                          Mark Davis (805) 499-5725 X 4142.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 25 mg/m2 on days 1
                          and 15 for four cycles. Drug 2: 10 mg/m2 (10
                          units/m2) on days 1 and 15 for four
                          cyclesDrug 3: 6 mg/m2 on days 1 and 15 for
                          four cycles. Drug 4: 375 mg/m2 on days 1 and
                          15 for four cycles. Drug 5: 5 mcg/kg on days
                          2 through 14 and 16 through 28 for foucycles
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 25 mg/m2. Drug 2: 10
                          mg/m2 (10 units/m2). Drug 3: 6 mg/m2. Drug 4:
                          375 mg/m2. Drug 5: 5 mcg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: IV, 10 and 50 mg
                          vials. Drug 2: IV, 15-unit vials. Drug 3: IV,
                          10 mg vials. Drug 4: IV, 100 and 200 mg
                          vials. Drug 5: SC
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum 4 months.
OTHER TREATMENT INFO.     END POINT: Primary: Dose-limiting toxicity;
                          degree of response to chemotherapy.
                          Secondary: Durability of response or disease
                          progression; rate of bacterial and
                          opportunistic infection.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for any of the following reasons: 1.
                          Unacceptable toxicity. 2. Documented complete
                          response followed by two cycles of study
                          treatment. 3. Documented partial response
                          after six cycles of study treatment. 4.
                          Disease progression at any time. 5. Clinical
                          congestive heart failure or a decrease in
                          left ventricular ejection fraction of 0.20 or
                          to < 0.45. 6. Pregnancy. 7. Desire of patient
                          to withdraw.
OTHER TREATMENT INFO.     MODIFICATION: Patients with bone marrow
                          involvement should receive no more than 75
                          percent of the full chemotherapy dose during
                          the first cycle. Hematologic toxicity: For
                          ANC < 1000/mm3 on day 1 of a cycle, hold
                          chemotherapy 1 week and continue G-CSF. For
                          ANC < 1000/mm3 on day 15, hold chemotherapy 1
                          week and begin G-CSF at 10 mcg/kg/day. G-CSF
                          may be increased to 15 - 20 mcg/kg/day, at
                          the discretion of the investigator, if ANC
                          remains < 1000/mm3. Discontinue G-CSF when
                          ANC > 10000/mm3. For platelets < 100000/mm3,
                          hold chemotherapy for 1 week unless values
                          are caused by bone marrow involvement; if
                          platelets are 75000 to < 100000/mm3 after 1
                          week, resume doxorubicin and vinblastine at
                          75 percent dose for the next cycle. If
                          platelets are 50000 - < 75000/mm3 after 1
                          week, resume doxorubicin and vinblastine at
                          50 percent dose for the next cycle. When
                          platelets are 100000 or higher, resume
                          chemotherapy at full dose. Hepatic toxicity:
                          For bilirubin 1.5 to < 3.0 mg/dl, reduce
                          doxorubicin and vinblastine doses to 50
                          percent of previous dose. For bilirubin 3.0
                          mg/dl or higher, reduce doxorubicin and
                          vinblastine to 25 percent of original dose;
                          if toxicity does not resolve in 1 week,
                          discontinue study medications. Renal
                          toxicity: If creatinine increases to 2.5
                          mg/dl or higher or creatinine clearance
                          decreases to 60 ml/min or less, discontinue
                          study medications. Discontinue study
                          medications for any of the following
                          conditions: Grade 3 or worse peripheral
                          neuropathy, pulmonary symptoms thought to be
                          caused by toxicity, and grade 3 cardiac
                          toxicity.
SUPPORTING AGENCY         National Institute of Allergy & Infectious
                          Diseases (ACTG), Amgen Incorporated.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents, Combined/*THERAPEUTIC
                          USE
MESH HEADING              Bleomycins/*THERAPEUTIC USE
MESH HEADING              Dacarbazine/*THERAPEUTIC USE
MESH HEADING              Doxorubicin/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Granulocyte Colony-Stimulating Factor/
                          *THERAPEUTIC USE
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Hodgkin's Disease/COMPLICATIONS/*DRUG THERAPY/
                          THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Vincristine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antineoplastic Agents, Combined)
CAS REGISTRY NUMBER       0 (ABVD protocol)
CAS REGISTRY NUMBER       62683-29-8 (Granulocyte Colony-Stimulating
                          Factor)
LAST REVISION DATE        941207
ENTRY MONTH               9202
CALIFORNIA                Kenneth Norris Cancer Hospital / LAC-USC 2020
                          Zonal Avenue Room 309 Los Angeles, CA 90033
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          920625 ACTU: 1203.
CALIFORNIA                University of Southern California / LAC-USC
                          Medical Center Bldg 5P21 / 1175 N Cummings
                          Street / Room 349 Los Angeles, CA 90033-1079
                          Contact: Luis Mendez (213) 343-8288 OPEN
                          920508 ACTU: 1201.
ILLINOIS                  Northwestern University Medical School / ACTG
                          Studies 303 East Superior Street Passavant
                          823 Chicago, IL 60611 Contact: Baiba Berzins
                          (312) 908-9636 OPEN 920702 ACTU: 2701.
ILLINOIS                  Illinois Masonic Med Ctr / Northwestern Univ
                          Med Schl Passavant Pavilion Room 823 / 303
                          East Superior Chicago, IL 60611 Contact:
                          Baiba L Berzins (312) 908-9636 OPEN 941125
                          ACTU: 2707.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard Indianapolis, IN
                          46202-5250 Contact: Beth Zwickl (317)
                          274-8456 OPEN 930518 ACTU: 2601.
MASSACHUSETTS             Boston City Hospital / AIDS Research Office
                          818 Harrison Avenue ACC 5th Floor Room 5D11
                          Boston, MA 02118 Contact: Beverly Byam (617)
                          534-5160 CLOSED 930730 ACTU: 0104.
MISSOURI                  Washington University School of Medicine 4511
                          Forest Park Pkwy Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0538
                          Contact: (314) 454-0058 OPEN 920218 ACTU:
                          2101.
MISSOURI                  St Louis Regional Hospital 5535 Del Mar / 6Th
                          Floor West Annex St Louis, MO 63112 Contact:
                          Michael Conklin (314) 879-6411 OPEN 920218
                          ACTU: 2102.
NEW YORK                  Saint Luke's Roosevelt Hospital 432 West 58th
                          Street Antenucchi Building Lobby Level ANT 1
                          New York, NY 10019 Contact: Julie Linksman
                          Rivera (212) 523-6743 CLOSED 930317 ACTU:
                          3401.
NEW YORK                  Mount Sinai School of Medicine / Clinical
                          Trials PO Box 1042 One Gustave L Levy Place
                          New York, NY 10029 Contact: Eileen Chusid
                          (212) 241-8903 Contact: (212) 241-7856 OPEN
                          920508 ACTU: 1801.
NEW YORK                  SUNY at Buffalo 462 Grider Street / BB109
                          Buffalo, NY 14215 Contact: Michelle Lewis
                          (716) 898-3932 Contact: (716) 898-3933 OPEN
                          921009 ACTU: 1102.
OHIO                      Children's Hospital 700 Children's Drive
                          Columbus, OH 43205-2696 Contact: Jane Hunkler
                          (614) 722-4460 Contact: (614) 722-6050 OPEN
                          940106 ACTU: 2302.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN ACTU:
                          2301.
 
62
UNIQUE IDENTIFIER         NIH/00137
PROTOCOL ID NUMBERS       NIAID ACTG 103
PROTOCOL TITLE            A Randomized Trial To Evaluate the Impact of
                          Maintaining Steady-State Concentrations of
                          Azidothymidine (AZT) Versus an Intermittent
                          Schedule of AZT Delivery in Children With
                          Symptomatic HIV Infection. AMENDED: ddI Arm
                          Removed, Open Only to Children With
                          Encephalopathy.
VERSION NUMBER & DATE     2 (930707)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Child
TRIAL CATEGORY            Neurologic Manifestations
PROTOCOL CHAIRS           CHAIR  Pizzo PA
GENERAL DESCRIPTION       PURPOSE: AMENDED 07/07/93: To evaluate
                          whether continuous infusion AZT will impact
                          neurodevelopmental deficits associated with
                          HIV infection or alter rate of encephalopathy
                          progression in children who have failed to
                          improve or shown progression of these
                          deficits despite optimal AZT therapy.
                          AMENDED: To assess whether didanosine (ddI)
                          will be better tolerated than AZT
                          administered by either continuous intravenous
                          deliver or oral administration (ddI arm
                          removed per amended version). To determine
                          whether ddI will achieve comparable clinical
                          efficacy as the continuous intravenous route
                          of delivery of AZT, and to assess whether
                          either or both of these regimens are superior
                          to that achieved with an intermittent AZT
                          dosage schedule. To determine whether there
                          are differences in patient or parent
                          (guardian) compliance between the three
                          treatment regimens. Original design: To
                          determine whether the pharmacokinetic profile
                          (bloodstream levels) of zidovudine (AZT)
                          influences its effectiveness on HIV infection
                          in children. That is, the study seeks to find
                          out whether there is a difference in the
                          effect of AZT when given as a continuous
                          intravenous infusion (and, if available, an
                          oral sustained release dose) compared to an
                          intermittent (not continuous) dose given
                          orally every 6 hours. The study also plans to
                          determine (1) whether there are differences
                          in the tolerance and side effects associated
                          with AZT when given on an intermittent
                          schedule as opposed to a steady-state
                          schedule; (2) the extent of variation from
                          patient to patient in AZT levels and whether
                          the plasma and cerebrospinal fluid levels of
                          AZT are related to the degree of therapeutic
                          effectiveness; and (3) whether there are
                          differences in the response of children who
                          acquired HIV infection perinatally (just
                          before, during, or just after the time of
                          birth) versus those who acquired HIV
                          infection by transfusion.
GENERAL DESCRIPTION       RATIONALE: One of the most serious effects of
                          HIV disease in children is neuropsychological
                          deterioration (relating to mental and nervous
                          system functioning). This complication
                          affects the vast majority of HIV infected
                          children. A previous study of continuous
                          intravenous administration of AZT in
                          pediatric patients with HIV infection showed
                          consistent and dramatic improvements of
                          symptoms in all patients that had shown
                          neurodevelopmental deficits or abnormalities.
                          These improvements were seen within 3 to 4
                          weeks after AZT treatment was started.
                          Neurodevelopmental improvements have been
                          sustained on AZT, usually showing steady
                          improvement which, in some patients, was
                          associated with restoration of pre-HIV
                          intellectual and neurological function. This
                          study also showed an increase in the IQ
                          scores of children receiving continuous
                          infusion of AZT who did not have overt
                          clinical evidence of encephalopathy (disease
                          of the brain). Thus changes in cognitive
                          function may be among the earliest signs of
                          AIDS encephalopathy and underscores the need
                          to start therapies that will treat the
                          central nervous system in patients who appear
                          to be clinically intact. A study comparing
                          continuous infusion to intermittent dosing of
                          AZT showed a significant increase in IQ
                          scores for those children receiving the
                          continuous dose compared to those treated
                          with the intermittent schedule. Although a
                          portable infusion pump allows patients to
                          receive continuous infusion of AZT, a
                          sustained release oral formulation that could
                          provide a continuous release of AZT into the
                          bloodstream would be highly desirable.
GENERAL DESCRIPTION       METHODOLOGY: AMENDED 07/07/93: Children with
                          progressive encephalopathy who have received
                          a minimum of 3 months of oral or intermittent
                          AZT or who have failed to improve following 6
                          months of optimal AZT will receive continuous
                          infusion AZT via a protable infusion pump.
                          AMENDED: The oral sustained relase has been
                          dropped and is now oral ddI 90 mg/m2 q8h.
                          Added has been a planned stratification for
                          randomization for patients who received any
                          antiretroviral therapy 4 or more weeks prior
                          to study entry. The informed consent was
                          modified to reflect ddI toxicities from adult
                          studies. Computerized Tomography radiation
                          dosimetry is now included. AMENDED: DROPPING
                          the DDI component and open only to CHILDREN
                          WITH ENCEPHALOPATHY meaning they are losing
                          milestones, this is equal to a P2 CDC rating
                          . Testing the difference in INTERMEDIATE VS
                          CONTINUOUS AZT. 12/1990. Original design:
                          Children are first evaluated for
                          randomization according to whether they have
                          or do not have evidence of neurodevelopmental
                          deficits at the time of the initial
                          pretreatment evaluation. Patients are
                          assigned to one of three groups, to receive
                          AZT (1) by continuous infusion; (2) by oral,
                          intermittent (every 6 hours) dosing; or (3)
                          by oral sustained-release dosing. If the oral
                          sustained-release formulation is not
                          available when this study begins, it will
                          begin with only the first two groups. The
                          sustained release preparation will be
                          evaluated as soon as it is available.
                          Patients will be tested to measure physical
                          or biological improvement in
                          neurodevelopmental function.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940425)
DISEASE STUDIED           Primary HIV infection, Encephalopathy.
DISEASES STATUS           AMENDED 07/07/93: Only HIV-related
                          encephalopathy patients eligible (i.e.,
                          children with progressive encephalopathy who
                          have received a minimum of 3 months of oral
                          or intermittent AZT or who have failed to
                          improve following 6 months of optimal AZT).
                          ORIGINAL DESIGN: AIDS: Children must have
                          clinical evidence of HIV infection as
                          demonstrated by the presence of one or more
                          of the definitively or presumptively
                          diagnosed indicator diseases as defined in
                          the CDC Surveillance definition of AIDS.
                          Children with lymphocytic interstitial
                          pneumonitis are included if they meet at
                          least one of the following conditions: (1) an
                          additional AIDS-defining opportunistic
                          infection; (2) recurrent serious bacterial
                          infections; (3) evidence of HIV
                          encephalopathy; (4) a wasting syndrome; or
                          (5) meet the definition of AIDS-related
                          complex (ARC) as follows: ARC: At least one
                          of the first three clinical findings and any
                          other listed below within 2 months of study
                          entry (or with two of the first three
                          findings): 1. Failure to thrive defined as
                          child who crosses (falls) two percentile
                          lines on the growth chart, or a child who is
                          in less than the fifth percentile for height
                          and weight and does not follow their growth
                          curve. 2. Persistent (= or > 2 months) or
                          recurrent oral candidiasis despite
                          appropriate therapy. 3. CD4+ = or < 500
                          cells. Additional clinical findings: o
                          Diarrhea (= or > 3 loose stools/day) that is
                          either persistent (> 3 months) or recurrent
                          (= or > 2 episodes resulting in dehydration
                          within a 2-month period). o Hepatomegaly. o
                          Splenomegaly. o Cardiomyopathy. o Nephropathy
                          manifested by nephrotic syndrome without
                          evidence of renal failure. o Two or more
                          episodes of herpes stomatitis within a 1-year
                          period. o Two or more episodes of recurrent
                          herpes zoster or chronic zoster defined at =
                          or > 30 days duration regardless of therapy.
                          Children < 15 months of age, who are thought
                          to have acquired HIV through perinatal
                          transmission and whose only laboratory
                          evidence of HIV infection is a positive
                          antibody test, must also have increased
                          immunoglobulin levels or decreased absolute
                          number of CD4 cells or a decreased
                          helper/suppressor ratio.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    NCI 89 C-102C
STUDY DESIGN              Open Label; Prospective; Randomized
PROTOCOL DETAILS          STUDY INTENT: Drug therapy, Administration
                          route comparison.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 75 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 52 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 4/75 (931027).
PROTOCOL DETAILS          DATE OF FIRST ENROLLMENT: 900321
PROTOCOL DETAILS          STUDY DURATION: 52 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 7 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: AMENDED 07/07/93:
                          Only HIV-related encephalopathy patients
                          eligible (i.e., children with progressive
                          encephalopathy who have received a minimum of
                          3 months of oral or intermittent AZT or who
                          have failed to improve following 6 months of
                          optimal AZT). ORIGINAL DESIGN: Eligibility
                          criteria used are similar to those being used
                          in the Multicenter Trial to Evaluate Oral
                          Retrovir in the Treatment of Children with
                          Symptomatic HIV Infection, currently
                          Protocol 88 C-92a. Children are included:
                          With overt encephalopathy as well as those
                          who may have a subclinical cognitive
                          impairment. Children must have laboratory
                          evidence of HIV infection as demonstrated by
                          either a positive viral culture (blood or
                          cerebrospinal fluid) or detectable serum P24
                          antigen or repeatedly positive test for HIV
                          antibody. HIV antibody must be determined by
                          federally licensed ELISA test and confirmed
                          by Western blot. Children with AIDS or ARC
                          must have at least one of the following
                          laboratory criteria indicative of immunologic
                          abnormality: o Hypergammaglobulinemia (IgG or
                          IgA) defined as immunoglobulin values > upper
                          limit of the age-adjusted normal. o
                          Hypogammaglobulinemia (IgG or IgA) defined as
                          immunoglobulin levels < lower limit of the
                          age-adjusted normal. o Absolute depression in
                          CD4+ cells to = or < 500 cells/mm3. o
                          Decreased helper/suppressor ratio to = or <
                          1.0. o Depressed in vitro mitogen response to
                          at least one antigen (pokeweed,
                          phytohemagglutinin, concanavalin A,
                          Staphylococcus aureus, tetanus toxoid,
                          Candida). Parent or guardian available to
                          give written informed consent. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 24 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. In presence of
                          abnormal bilirubin (age adjusted).
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
                          Estimated.
PATIENT INCLUSION CRIT.   OTHER: White blood cells (WBC) >= 1500
                          cells/mm3. Neutrophil count >= 750 cells/mm3.
PATIENT AGE               AGE: 03 Months - 12 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Pubertal
                          females should be screened for pregnancy.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed within 4 weeks of
                          study entry: Immunoglobulin for
                          thrombocytopenia.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Steroids for
                          children with lymphocytic interstitial
                          pneumonitis (LIP) who are steroid dependent.
                          Maintenance amphotericin B and
                          antituberculosis chemotherapy. Immunoglobulin
                          therapy for children who develop at least
                          three serious bacterial infections while
                          receiving zidovudine (AZT) therapy.
                          Prophylactic therapy for children who have
                          had a previous episode of Pneumocystis
                          carinii pneumonia (PCP) and who are receiving
                          such therapy.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following are excluded: Serious bacterial,
                          fungal, or parasitic infections requiring
                          parental therapy, at the time of study entry.
                          Lymphocytic interstitial pneumonitis (LIP)
                          and no additional AIDS-defining indicator
                          disease as specified in the CDC Surveillance
                          Case Definition for AIDS. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 2 Months. 13 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Unspecified.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Excluded: Active alcohol or
                          drug abuse.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 4 weeks of
                          study entry: Lymphocyte transfusion for
                          immune reconstitution. Excluded within 3
                          months of study entry: Bone marrow
                          transplant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks of
                          study entry: Other antiretroviral agents
                          including ribavirin, HPA-23, dideoxycytosine
                          (ddC), soluble CD4, and dideoxyadenosine
                          (ddA) / didanosine (ddI). Immunomodulating
                          agents including steroids, interferon,
                          isoprinosine, and IL-2 not specifically
                          allowed. Immunoglobulin not specifically
                          allowed. Excluded within 2 weeks of study
                          entry: Any other experimental therapy. Drugs
                          that cause prolonged neutropenia or
                          significant nephrotoxicity.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Clofazimine,
                          ansamycin (or other experimental agents or
                          agents that may modify zidovudine (AZT)
                          toxicity or safety) for active chronic
                          opportunistic infection at time of study
                          entry. Chronic use of drugs that are
                          metabolized by hepatic glucuronidation (and
                          may alter the metabolism of AZT) (e.g.,
                          aetaminophen). Prophylaxis for Pneumocystis
                          carinii pneumonia (PCP) for children who have
                          not had a previous episode of PCP, oral
                          candidiasis, or otitis media. Immunoglobulin
                          therapy not specifically allowed.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          are excluded: Serious bacterial, fungal, or
                          parasitic infections requiring parental
                          therapy, at the time of study entry.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Excluded: Unable to be followed
                          for the duration of the study (24 weeks).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 Videx
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Lisa Behrens (800) 722-9292 X 3633.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 2400
                          West Lloyd Expressway Evansville, IN
                          47721-0001 Contact: DDI Information (800)
                          662-7999.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Arm 1: 480 mg/m2/day
                          or 20 mg/m2/hour. Arm 2: 180 mg/m2. Arm 3:
                          Pending additional data. (AMENDED: ddI
                          substitute). Drug 2: 90 mg/m2 q8h
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Arm 1: 480 mg/m2. Arm
                          2: 720 mg/m2. Arm 3: Pending additional data.
                          (AMENDED: ddI substitute). Drug 2: 180 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Arm 1: Intravenous,
                          via portable, programmable infusionpump. Drug
                          2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Drug 1: 24 weeks,
                          minimum. Drug 2: 24 weeks.
OTHER TREATMENT INFO.     END POINT: Evaluation of neurodevelopmental
                          system; comparative changes in other measures
                          of efficacy and toxicity.
OTHER TREATMENT INFO.     DISCONTINUE: Discontinue treatment for the
                          following: Severe allergic reaction such as
                          exfoliative erythroderma, anaphylaxis, or
                          vascular collapse. Noncompliance: Not
                          adhering to the dosing plan or failing to
                          keep three scheduled consecutive clinical
                          appointments. Requiring a cumulative total of
                          25 red blood cell transfusions or neutropenia
                          (< 500 pmns) after two dose reductions (i.e.,
                          50 percent of the original dosage). Requiring
                          treatment with an experimental agent or
                          another drug with known antiretroviral
                          activity.
OTHER TREATMENT INFO.     MODIFICATION: For grade 3 or 4 hematologic
                          toxicity: Reduce dose by approximately 25
                          percent following temporary discontinuation
                          of zidovudine (AZT). For progressive bone
                          marrow suppression and grade 3 or 4 toxicity
                          as defined below: Temporarily withhold drug
                          until hematologic parameters stabilize. For
                          hemoglobin levels that fall to < 8 g/dl:
                          transfuse. Withhold AZT: For transfusion
                          dependence > 4 weeks. For a decrease in
                          neutrophil count to < 500 cells/mm3 on two
                          consecutive determinations 24 hours apart.
                          For decrease in platelet count to = or <
                          25000 platelets/mm3. Resume therapy at 25
                          percent dose reduction once hematologic
                          abnormalities return to baseline. Increase to
                          original level if these baseline levels are
                          stable for 1 month after dose reduction.
SUPPORTING AGENCY         National Cancer Institute Pediatric
                          Intramural Studies, National Institute of
                          Allergy & Infectious Diseases (ACTG).
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Central Nervous System Diseases/*DRUG THERAPY/
                          ETIOLOGY
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Randomized Controlled Trials
MESH HEADING              Zidovudine/*ADMINISTRATION & DOSAGE/
                          PHARMACOKINETICS/THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940425
ENTRY MONTH               8909
DISTRICT OF COLUMBIA      Children's Hospital National Medical Center
                          111 Michigan Avenue NW Washington, DC 20010
                          Contact: Sherri Plumley (202) 939-3558 CLOSED
                          931027 ACTU: 5016.
FLORIDA                   University Hospital of Jacksonville Florida
                          655 West 8th Street Jacksonville, FL 32209
                          Contact: Dr Sharon Paryani (904) 350-6872
                          CLOSED 931027.
MARYLAND                  Walter Reed / USUHS / Pediatrics 4301 Jones
                          Bridge Road Bethesda, MD 20889-4799 Contact:
                          Nicki Nau (301) 829-0223 Contact: . CLOSED
                          931027.
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN 940425.
MARYLAND                  University of Maryland School of Medicine /
                          Pediatrics 120 Penn Street Baltimore, MD
                          21201 Contact: Sue Lovelace (410) 706-8220
                          CLOSED 931027 ACTU: 3702.
NORTH CAROLINA            Duke University Medical Center / Pediatrics
                          Box 3499 Durham, NC 27710 Contact: John
                          Swetnam (919) 684-6335 CLOSED 931027 ACTU:
                          4701.
NEW YORK                  The Children's Hospital at Albany Medical
                          Center Department of Pediatrics New Scotland
                          Avenue Albany, NY 12208 Contact: Dr Martha
                          Lepow (518) 432-1501 CLOSED 931027.
 
63
UNIQUE IDENTIFIER         NIH/00682
PROTOCOL ID NUMBERS       NIAID 94 I-206
PROTOCOL TITLE            A Phase I/II Pilot Study of the Safety of the
                          Adoptive Transfer of Syngeneic Gene-Modified
                          Cytotoxic T Lymphocytes in HIV-Infected
                          Identical Twins.
VERSION NUMBER & DATE     (940808)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Walker RE
GENERAL DESCRIPTION       PURPOSE: To compare the safety, tolerance,
                          and efficacy of infusions of activated,
                          culture-expanded CD8+ (cytotoxic) lymphocytes
                          with or without gene modification when
                          obtained from HIV-seronegative identical
                          twins and administered to their HIV-infected
                          siblings.
GENERAL DESCRIPTION       RATIONALE: Transplantation of hematopoietic
                          elements has been shown to correct the immune
                          defects in certain primary immune deficiency
                          diseases but has resulted in only temporary
                          immunologic improvement in AIDS patients.
                          This study assesses the potential value of
                          genetically modifying T-lymphocytes in an
                          attempt to prevent or control HIV infection.
                          It will also permit the effects of gene
                          modification of the cells to be distinguished
                          from those effects of activated T-cell
                          infusions alone.
GENERAL DESCRIPTION       METHODOLOGY: Peripheral blood lymphocytes are
                          obtained by periodic apheresis from the
                          HIV-seronegative identical twin of each
                          HIV-positive patient. Cells are activated
                          with OKT3 antibody and interleukin-2 and
                          expanded. For 33 of 43 donors, cells are
                          genetically modified prior to ex-vivo
                          expansion. Prior to the randomization stage
                          of the study, a separate group of three
                          HIV-seropositive patients receive
                          gene-modified lymphocytes at a dose of 10
                          million cells. If no dose-limiting toxicity
                          (DLT) occurs, subsequent 6-patient cohorts
                          are randomized to receive single infusions of
                          unmodified lymphocytes (10 billion cells) or
                          modified lymphocytes (100 million, 1 billion,
                          or 10 billion cells). The expanded
                          lymphocytes are infused over 60 minutes into
                          the HIV-seropositive patient via a peripheral
                          or central vein. Patients without DLT after
                          their initial infusion may receive up to six
                          additional infusions at 8-week intervals;
                          patients who initially received unmodified
                          cells receive the same dose and those who
                          received modified cells receive the assessed
                          maximum safe dose. Additionally, up to four
                          new patients may receive unmodified
                          lymphocytes and up to 12 new patients may
                          receive modified lymphocytes. Patients are
                          followed daily for 4 days after each
                          infusion, then weekly for the duration of
                          treatment.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941101)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: HIV seropositive, with an
                          HIV-seronegative identical twin, as confirmed
                          by ELISA, PCR, or Western blot. NOTE: If CD4
                          count is < 500 cells/mm3 at study entry,
                          patient must have been on an FDA-approved or
                          expanded-access antiretroviral therapy for at
                          least 2 months. NOTE: Patients with Kaposi's
                          sarcoma are eligible, provided they have
                          received no systemic therapy for KS within 4
                          weeks prior to study entry. Diagnosis of KS
                          must be confirmed by biopsy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    BB-IND 5610. T-9401
STUDY DESIGN              Open Label; Comparative; Randomized;
                          Controlled; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Immunotherapy, Drug safety,
                          Drug tolerance, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 43 patients. (33 patients
                          receive modified T-lymphocytes; 10 patients
                          receive unmodified T-lymphocytes)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Approximately
                          15 months.
PROTOCOL DETAILS          STUDY DURATION: Approximately 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity with an
                          HIV-seronegative identical twin. 2. Life
                          expectancy greater than 6 months. NOTE: If
                          CD4 count is < 500 cells/mm3 at study entry,
                          patient must have been on an FDA-approved or
                          expanded-access antiretroviral therapy for at
                          least 2 months. NOTE: Patients with Kaposi's
                          sarcoma are eligible, provided they have
                          received no systemic therapy for KS within 4
                          weeks prior to study entry. Diagnosis of KS
                          must be confirmed by biopsy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: At least 2 months
                          of prior antiretroviral therapy in patients
                          with CD4 count < 500 cells/mm3 at study
                          entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. No
                          abstinence or no agreement to use barrier
                          methods of birth control / contraception
                          during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Recent history of substance
                          abuse unless evidence is provided of ongoing
                          therapeutic intervention (i.e., medical
                          therapy or counseling) to control such abuse.
                          Unwilling to appropriately notifiy all
                          current sexual partners of individual's
                          HIV-seropositive status and the risk of
                          infection.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Systemic therapy
                          for Kaposi's sarcoma within 4 weeks prior to
                          study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients (recipients) with the
                          following symptoms or conditions are
                          excluded: 1. Lymphoma. 2. Serious
                          psychological or emotional illness. Donors
                          with the following symptoms or conditions are
                          excluded: 1. Untreated or inadequately
                          treated medical condition (e.g.,
                          cardiopulmonary disease, acute infection)
                          that precludes apheresis. 2. Serologic
                          positivity for Epstein Barr virus,
                          Cytomegalovirus, Hepatitis B, or Hepatitis C,
                          if and only if the recipient twin is
                          seronegative for the corresponding virus.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0146  Lymphocytes, Activated
MANUFACTURERS             Drug 1: National Institute of Allergy and
                          Infectious Diseases 9000 Rockville Pike
                          Building 10 Room 7D43 Bethesda, MD 20892
                          Contact: Candace Kurtz (301) 496-9320
                          Contact: (301) 402-0586.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 10 million to 10
                          billion cells q 8 weeks for six infusions
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV)
OTHER TREATMENT INFO.     END POINT: Primary: Safety of administering
                          syngeneic genetically modified CD8+ cytotoxic
                          T-lymphocytes. Secondary: Effects on primary
                          disease status (CD4 count, HIV burden, p24
                          antigen), longevity of genetically modified
                          transplanted T-lymphocytes.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Dose-limiting
                          toxicity. 2. Development of another
                          unexpected, life-threatening complication. 3.
                          Profound disease progression or other medical
                          complication that precludes further therapy.
                          4. Refusal of patient to continue study or
                          patient noncompliance.
SUPPORTING AGENCY         National Institute of Allergy and Infectious
                          Diseases.
MESH HEADING              AIDS-Related Complex/IMMUNOLOGY/*THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/IMMUNOLOGY/
                          *THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/IMMUNOLOGY/*THERAPY
MESH HEADING              Human
MESH HEADING              Immunotherapy, Adoptive
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              T-Lymphocytes/IMMUNOLOGY/*TRANSPLANTATION
MESH HEADING              Transplantation, Isogeneic
LAST REVISION DATE        941101
ENTRY MONTH               9411
MARYLAND                  National Institute of Allergy & Infectious
                          Diseases 9000 Rockville Pike / Clinical
                          Center Bethesda, MD 20892 Contact: Betsey
                          Herpin (800) 772-5464 X 304Contact: Chris
                          Boenning (800) 772-5464 X 401OPEN / USA
                          accrual 941101.
 
64
UNIQUE IDENTIFIER         NIH/00592
PROTOCOL ID NUMBERS       NIAID 92 I-125
PROTOCOL TITLE            A Study of Viral Burden in Peripheral Blood
                          Versus Lymphoid Tissue in Human
                          Immunodeficiency Virus Infected Individuals.
VERSION NUMBER & DATE     (940308)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Stanley SK
PROTOCOL CHAIRS           CO-CHAIR  Fauci AS, Pantaleo G, Gr
GENERAL DESCRIPTION       PURPOSE: AMENDED 02/94: Enrollment limited to
                          long-term immunologic nonprogressors.
                          ORIGINAL: To determine the relative burden of
                          HIV and the relative degree of HIV expression
                          in the peripheral blood mononuclear cells
                          (PBMC) versus the lymph nodes in individual
                          patients with HIV infection. To delineate the
                          precise nature of the perturbations in V-beta
                          subsets of T cells in the peripheral blood
                          versus the lymph nodes of HIV-infected
                          individuals in order to pursue the role of
                          superantigens in the immunopathogenesis of
                          HIV infection. To examine the effect of
                          therapy on viral burden and HIV expression in
                          lymph node versus PBMC.
GENERAL DESCRIPTION       RATIONALE: Recent studies have demonstrated
                          that there is ten times more virus (per
                          constant number of CD4 T cells) in the lymph
                          nodes than in the PBMC of HIV-infected
                          patients with generalized lymphadenopathy,
                          indicating that the lymph node may be the
                          major reservoir of HIV presence and
                          expression in the body. It is important to
                          establish whether this situation exists in a
                          broad spectrum of HIV patients at various
                          stages of infection from initial acute
                          infection through advanced disease. If
                          patients with early asymptomatic disease are
                          shown to have substantial viral replication
                          in lymph nodes at a time when their
                          peripheral blood reflects a relative latency,
                          this finding will provide a basis for
                          treating patients earlier in the course of
                          their HIV infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients will have no more than
                          400 cc of blood drawn during their
                          participation on the study and will undergo
                          surgical removal under local anesthesia of a
                          lymph node from the groin, armpit, or neck.
PROTOCOL PHASE            Immunopathogenesis
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940308)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions. AMENDED 02/94 TO LIMIT ENROLLMENT
                          AS FOLLOWS: 1. Documented HIV infection for >
                          7 years. 2. Long-term immunologic
                          nonprogression. 3. CD4 count > 500 cells/mm3.
                          4. No prior antiviral therapy. 5. No AIDS
                          dementia or AIDS-related malignancy other
                          than minimal Kaposi's sarcoma. ORIGINAL ENTRY
                          CRITERIA: 1. Documented HIV infection. 2. CD4
                          count of any value. 3. Antiretroviral therapy
                          permitted. 4. No AIDS dementia or
                          AIDS-related malignancy other than minimal
                          Kaposi's sarcoma.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Nonrandomized
PROTOCOL DETAILS          STUDY INTENT: Immunology.
PROTOCOL DETAILS          PROJECTED ACCRUAL: UNLIMITED patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 20/UNLIMITED (941116).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have (per 02/94 amendment): 1. Documented HIV
                          infection for > 7 years. 2. Long-term
                          immunologic nonprogression. 3. CD4 > 500
                          cells/mm3. 4. No prior antiviral therapy. 5.
                          No AIDS dementia or AIDS-related malignancy
                          other than minimal Kaposi's sarcoma. 6.
                          Palpable lymph node. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: Normal platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 500 cells/mm3. ( 500 -
                          600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 1000 cells/mm3.
                          PT and PTT normal.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Prophylaxis
                          for opportunistic infections.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          antiviral therapy. 2. Aspirin within 1 week
                          prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Bleeding diathesis. 2. Need for chronic
                          aspirin therapy.
OTHER TREATMENT INFO.     END POINT: Measurements of viral burden.
SUPPORTING AGENCY         National Institute of Allergy and Infectious
                          Diseases.
MESH HEADING              AIDS-Related Complex/*IMMUNOLOGY/PATHOLOGY
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *IMMUNOLOGY/PATHOLOGY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*IMMUNOLOGY/PATHOLOGY
MESH HEADING              Human
MESH HEADING              Lymph Nodes/IMMUNOLOGY/*PATHOLOGY
MESH HEADING              Lymphoid Tissue/IMMUNOLOGY/*PATHOLOGY
MESH HEADING              Male
MESH HEADING              Middle Age
LAST REVISION DATE        940308
ENTRY MONTH               9403
MARYLAND                  National Institute of Allergy & Infectious
                          Diseases 9000 Rockville Pike / Bldg 10 / Room
                          11B13 Bethesda, MD 20892 Contact: Barbara
                          Baird (301) 402-0980 X 420OPEN / USA Accrual
                          940308.
 
65
UNIQUE IDENTIFIER         NIH/00055
PROTOCOL ID NUMBERS       NIAID 91 CC-143
PROTOCOL TITLE            Open-Label Trial to Evaluate IL-2 in Patients
                          With HIV and Kaposi's Sarcoma. (Formerly A
                          Phase I-II Study of the Combination of
                          Azidothymidine and Interleukin-2 in the
                          Treatment of AIDS Patients.)
VERSION NUMBER & DATE     (940616)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Kovacs JA
GENERAL DESCRIPTION       PURPOSE: AMENDED 8/93: To evaluate the effect
                          of interleukin-2 (IL-2) in patients with HIV
                          and cutaneous Kaposi's sarcoma (KS). PER
                          6/21/91 AMENDMENT: To determine whether the
                          changes that occur following a single course
                          of IL-2 will recur or be enhanced with repeat
                          courses and to evaluate the safety of repeat
                          courses. ORIGINAL: To evaluate the toxicity
                          and obtain preliminary information on the
                          effectiveness of the combination of
                          zidovudine (AZT) and IL-2 in patients with
                          AIDS.
GENERAL DESCRIPTION       RATIONALE: AZT extends the survival of some
                          patients with AIDS but is not 100 percent
                          effective, and there is a need for the
                          development of more effective treatments for
                          AIDS and related disorders. IL-2 is a protein
                          that is naturally produced by lymphocytes,
                          but lymphocytes from patients with AIDS are
                          not able to produce this protein normally. In
                          preliminary studies, IL-2 improved some of
                          the immunological functions that are abnormal
                          in AIDS patients. (Immunological functions
                          aid the body in fighting infections, such as
                          AIDS). The combination of an antiviral agent
                          such as AZT with an immunomodulatory agent
                          such as IL-2 may provide beneficial effects
                          that are not provided by either agent alone.
                          Since the drugs have not been used in
                          combination in AIDS patients, a study is
                          needed to evaluate the toxicity of the
                          combination.
GENERAL DESCRIPTION       METHODOLOGY: AMENDMENT 8/93: Newly enrolled
                          patients with HIV and Kaposi's sarcoma
                          receive IL-2 therapy. AMENDMENT: Per 6/21/91
                          amendment, up to six patients previously
                          enrolled in the protocol who developed no
                          grade 3/4 toxicity receive repeat doses of
                          IL-2 (3 MU/day for 5 days) approximately
                          every 2 months. The patients receive AZT (100
                          mg 5 times daily). ORIGINAL: At the beginning
                          of the study, patients take AZT, either
                          continuing their previous AZT therapy or
                          starting oral AZT. After at least 6 weeks AZT
                          treatment and 2 weeks after the last dosage
                          change, patients are hospitalized for IL-2
                          treatment. IL-2 is given by continuous
                          infusion for 3-weeks through a vein in the
                          neck. The dose of IL-2 depends on the
                          experience of previous patients. After the 3
                          weeks, patients are discharged, but continue
                          to receive AZT for an additional 2 months.
                          During the study, blood samples are taken
                          periodically and skin biopsies of KS lesions
                          are taken before and after the 9 week
                          treatment period for those patients with KS.
                          If the patient appears to have benefited from
                          the treatment, AZT may be continued for up to
                          1 year and IL-2 may be given at the same dose
                          for 3-week periods, but not more than once
                          every 6 weeks.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940502)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: AMENDED 8/93: AIDS with
                          histological evidence of cutaneous Kaposi's
                          sarcoma. REQUIRED PER 6/21/91 AMENDMENT: 1.
                          Laboratory values of grade 1 or 2. 2. Prior
                          participation on NIAID 87 I-74 (Requirement
                          not applicable to patients currently being
                          enrolled).
ELIGIBILITY               AIDS / KS.
OTHER PROTOCOL NUMBERS    IRP 001. Project number 88174. IND/IDE number
                          BB2683
STUDY DESIGN              Open Label; 5-Arm; Dose Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug toxicity, Combination drug
                          therapy, Immunotherapy, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 1 year.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 18/30 (901105).
PROTOCOL DETAILS          DATE OF FIRST ENROLLMENT: 880401
PROTOCOL DETAILS          STUDY DURATION: 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Serologic or culture evidence of
                          infection with HIV and histological evidence
                          of cutaneous Kaposi's sarcoma. Performance
                          status: 0 - 1, where grade 0 is fully active
                          and grade 1 is restricted in physically
                          strenuous activity but fully active. Ability
                          and willingness to take AZT (original
                          design). [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 10 g/dl. prior to drug therapy.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 200 cells/mm3. (200 -
                          300 - 400 - 500 - 600 - 700 - 800 plus).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE: < 1.6 x ULN. (ULN = upper limit
                          of normal).
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 1500 cells/mm3.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Negative pregnancy test within 7 days of
                          study entry. Not breast-feeding. Abstinence
                          or agree to use barrier methods of birth
                          control / contraception during the study and
                          for 30 days after.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed if stopped 4 weeks
                          prior to study entry: Chemotherapy.
                          Corticosteroid therapy. Experimental therapy
                          other than zidovudine (AZT).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Positive pregnancy test within 7 days of
                          study entry. Breast-feeding. No abstinence or
                          no agreement to use barrier methods of birth
                          control during study and for 30 days after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks of
                          study entry: Chemotherapy. Corticosteroid
                          therapy. Experimental therapy other than
                          zidovudine (AZT).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded:
                          Dideoxyinosine (ddI) and dideoxycytidine
                          (ddC).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy other than Kaposi's sarcoma. 2.
                          Concurrent opportunistic infection other than
                          oropharyngeal candidiasis or herpes simplex.
                          3. Significant cardiac, pulmonary, or central
                          nervous system disease.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unable to provide informed
                          consent.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0021  Interleukin-2
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Cetus Corporation 1400 Fifty-Third
                          Street Emeryville, CA 94608 Contact: Dr Gwen
                          Fyfe (510) 601-3169.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg q4h, adjusted
                          to 100 mg q4h for toxicity if needed. Drug 2:
                          After 6 weeks of zidovudine (AZT) and at
                          least 2 weeks after last AZT dose adjustment:
                          0.25 million units/day (MU/d) or 1.0 MU/d or
                          2.0 MU/d or 3.0 MU/d or 4.0 MU/d
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 400 mg or 800 mg. Drug
                          2: 0.25 million units (MU) or 1.0 MU or 2.0
                          MU or 3.0 MU or 4.0 MU
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: PO. Drug 2: IV
                          infusion (continuous)
OTHER TREATMENT INFO.     TREATMENT DURATION: Drug 1: 9 weeks - 1 year,
                          depending on individual response. Drug 2: 3
                          weeks, with additional 3-week courses every 6
                          weeks, up to 1 year after entry, depending on
                          individual response. PER AMENDMENT: repeat
                          courses administered at 2-month intervals.
OTHER TREATMENT INFO.     DISCONTINUE: Patients will be removed from
                          the study for the following reasons: o Grade
                          3 or 4 toxicity of greater than 4 weeks
                          duration while off both drugs. NOTE: Per
                          06/16/94 amendment, patients with Gilbert's
                          disease who have elevated bilirubin may
                          continue IL-2. o Development of a
                          life-threatening infection or malignancy. o
                          Progressive Kaposi's sarcoma that requires
                          alternative therapy. o Patient
                          non-compliance.
OTHER TREATMENT INFO.     MODIFICATION: Dosages will be modified at the
                          designated toxicity grades (toxicity grades
                          are defined by the of protocol) while
                          patients are on zidovudine (AZT) alone: o
                          Grade 2 - no change or decrease AZT by 50
                          percent. o Grade 3 - decrease AZT by 50
                          percent. o Grade 4 - discontinue AZT. The
                          drug may be restarted at a lower dose if
                          there is evidence of clinical or laboratory
                          improvement. Dosages will be modified at the
                          designated toxicity grades (as defined by the
                          protocol) while patients are on AZT plus
                          interleukin 2 (IL-2): o Grade 2 - no change
                          or decrease IL-2 to next lowest dose. o Grade
                          3 anemia - no change. o Grade 3 other than
                          anemia - decrease IL-2 to next lowest dose or
                          stop both drugs. If toxicity continues after
                          dose reduction, stop IL-2. Drugs may be
                          restarted at a lower dose if there is
                          evidence of clinical or laboratory
                          improvement. o Grade 4 - discontinue both
                          drugs. Drugs may be restarted at a lower dose
                          if there is evidence of clinical or
                          laboratory improvement. NOTE: Per 06/16/94
                          amendment, in patients with Gilbert's disease
                          who have bilirubin > 5 mg/dl, hold IL-2 until
                          level decreases to < 3.0 mg/dl.
SUPPORTING AGENCY         National Institute of Allergy and Infectious
                          Diseases.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Adult
MESH HEADING              Drug Evaluation
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Interleukin-2/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/DRUG THERAPY
MESH HEADING              Zidovudine/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS
CAS REGISTRY NUMBER       0 (Interleukin-2)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940502
ENTRY MONTH               8904
MARYLAND                  National Institute of Allergy & Infectious
                          Diseases 9000 Rockville Pike Clinical Center
                          Bethesda, MD 20892 Contact: Susan Vogel (800)
                          772-5464 X 403Contact: Donna O'Neill (301)
                          402-0566 OPEN / USA accrual 930802.
 
66
UNIQUE IDENTIFIER         NIH/00571
PROTOCOL ID NUMBERS       NCI 94 C-35
PROTOCOL TITLE            A Phase I/II Study to Evaluate the Safety,
                          Toxicity, and Preliminary Efficacy of
                          Combinations of Lamivudine (3TC), Zidovudine
                          (AZT), and Didanosine (ddI) in Children With
                          HIV Infection.
VERSION NUMBER & DATE     (931026)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the pharmacokinetic
                          interactions, toxicity, and tolerability of
                          combinations of zidovudine (AZT) and
                          lamivudine (3TC), didanosine (ddI) and 3TC,
                          and all three agents in children with HIV
                          infection. Methodology: Patients with no
                          previous or less than 6 weeks of prior
                          antiretroviral therapy are randomized to Arm
                          A; those with prior therapy are randomized to
                          Arm B. Patients on Arm A receive AZT/ddI/3TC
                          but will be assigned alternately to two
                          different AZT dose levels (90 or 180
                          mg/m2/dose). Patients on Arm B are assigned
                          to a treatment regimen and dose level based
                          on their past medical and treatment history,
                          as follows: those with prior toxicity to ddI
                          receive AZT/3TC; those with prior toxicity to
                          AZT receive ddI/3TC; and those with prior
                          toxicity to both AZT and ddI or with
                          progressive HIV infection receive AZT/ddI/3TC
                          (with AZT dose of 90 mg/m2).
GENERAL DESCRIPTION       METHODOLOGY: Patients with no previous or
                          less than 6 weeks of prior antiretroviral
                          therapy are randomized to Arm A; those with
                          prior therapy are randomized to Arm B.
                          Patients on Arm A receive AZT/ddI/3TC but
                          will be assigned alternately to two different
                          AZT dose levels (90 or 180 mg/m2/dose).
                          Patients on Arm B are assigned to a treatment
                          regimen and dose level based on their past
                          medical and treatment history, as follows:
                          those with prior toxicity to ddI receive
                          AZT/3TC; those with prior toxicity to AZT
                          receive ddI/3TC; and those with prior
                          toxicity to both AZT and ddI or with
                          progressive HIV infection receive AZT/ddI/3TC
                          (with AZT dose of 90 mg/m2).
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940419)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions. 1. Class P-1b (asymptomatic) HIV
                          infection with the following age-corrected
                          CD4 count: < 1 year of age - 1750 cells/mm3;
                          1-2 years - 1000 cells/mm3; 2-6 years - 750
                          cells/mm3; 6-17 years - 500 cells/mm3. OR 2.
                          Previously treated patients with class P-1b
                          HIV infection with a 33 percent decline in
                          CD4 count or percentage or a decrease to
                          below 20 percent, confirmed by at least two
                          measurements 4 weeks apart. OR 3. Class P-2
                          (symptomatic) infection with toxicity to
                          antiretroviral therapy. OR 4. Class P-2
                          infection with progressive HIV disease while
                          on antiretroviral therapy. Progressive
                          disease is defined as: o Deterioration in
                          neuropsychological function o Weight loss or
                          failure to thrive o Organomegaly or
                          lymphadenopathy not associated with
                          opportunistic infection o Two or more serious
                          HIV-related opportunistic infections o
                          Decline in CD4 counts as described for P-1b
                          patients.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    FDA 225A. NUCA 2005
STUDY DESIGN              Randomized; 2-Arm; Drug Combination; Dose
                          Comparison; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Pharmacokinetics, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: Class P-1b (asymptomatic) or P-2
                          (symptomatic) HIV infection with specific
                          disease markers as described in the Disease
                          Status field. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl. (Transfusion
                          permitted).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3. (IVIG
                          allowed).
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   OTHER: WBC >= 100 cells/mm3 OR absolute
                          neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 03 Months - 17 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior
                          antiretroviral therapy (except within the 2
                          weeks immediately preceding study entry).
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Maintenance therapy for stable mycobacterial
                          or CMV infection. 2. Long-term suppression
                          for mucosal candidiasis or mucocutaneous
                          herpes virus infections.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 18 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy within 2 weeks prior to study entry.
                          2. Chemotherapeutic or immunomodulating
                          agents within 1 month prior to study entry
                          (except for G-CSF as part of antiretroviral
                          regimen, corticosteroids for LIP or reactive
                          airway disease, or IVIG for prevention of
                          bacterial infections or treatment for
                          thrombocytopenia).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Induction
                          therapy or ongoing treatment for active
                          opportunistic infections, except as
                          specifically allowed.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0126  Lamivudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 3TC
TRADE NAME OF SUBSTANCE   Drug 3 Videx
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Glaxo Incorporated 5 Moore Drive
                          Research Triangle Park, NC 27709 Contact:
                          Patti Gage (800) 334-0089.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 90 or 180 mg/m2 q 6
                          hr. Drug 2: 4 mg/kg q 12 hr. Drug 3: 135
                          mg/m2 q 12 hr
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 360 or 720 mg/m2. Drug
                          2: 8 mg/kg. Drug 3: 270 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
SUPPORTING AGENCY         National Cancer Institute Pediatric
                          Intramural Studies.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Antiviral Agents/*ADVERSE EFFECTS/
                          PHARMACOKINETICS
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Didanosine/*ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Reverse Transcriptase/*ANTAGONISTS & INHIB
MESH HEADING              Zidovudine/*ADVERSE EFFECTS/PHARMACOKINETICS
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
CAS REGISTRY NUMBER       EC 2
LAST REVISION DATE        940419
ENTRY MONTH               9402
CALIFORNIA                Children's Hospital of Los Angeles 4650
                          Sunset Boulevard Los Angeles, CA 90027
                          Contact: Lin Woods (213) 669-4537 OPEN
                          940330.
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN / USA Accrual 940203.
 
67
UNIQUE IDENTIFIER         NIH/00569
PROTOCOL ID NUMBERS       NCI 93 C-70
PROTOCOL TITLE            A Phase I/II Assessment of
                          Dose-Range/Escalation, Kinetics, Safety, and
                          Preliminary Efficacy of Oral Rifabutin
                          Suspension for the Prophylaxis of
                          Mycobacterium avium Complex (MAC) Bacteremia
                          in Pediatric Patients Infected With Human
                          Immunodeficiency Virus and Low CD4+ Cell
                          Counts.
VERSION NUMBER & DATE     (931026)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To assess single and multiple dose
                          pharmacokinetics, microbiologic and clinical
                          effects, and the safety and relative efficacy
                          of three dose levels of rifabutin
                          administered as prophylaxis against
                          Mycobacterium avium Complex (MAC) in children
                          with HIV infection and low CD4 counts.
                          Methodology: Patients continue their current
                          antiretroviral therapy with zidovudine (AZT),
                          didanosine (ddI), dideoxycytidine (ddC), or
                          some combination thereof. They receive either
                          5, 10, or 15 mg/kg rifabutin daily.
GENERAL DESCRIPTION       METHODOLOGY: Patients continue their current
                          antiretroviral therapy with zidovudine (AZT),
                          didanosine (ddI), dideoxycytidine (ddC), or
                          some combination thereof. They receive either
                          5, 10, or 15 mg/kg rifabutin daily.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940419)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Class P-1B (asymptomatic) or
                          class P-2 (symptomatic) HIV infection. 2. CD4
                          count < 100 cells/mm3 if >= 2 years of age OR
                          < 200 cells/mm3 if < 2 years of age. 3.
                          Negative for MAI on two blood cultures on two
                          consecutive visits. 4. No previous or current
                          disseminated infection due to MAC or other
                          mycobacterial infections. 5. No active
                          opportunistic infection OTHER THAN oral
                          candidiasis.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Dose Escalating; Drug Tolerance;
                          Pharmacokinetic; Drug Combination; Dose
                          Ranging
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug safety,
                          Drug efficacy, Pharmacokinetics, Combination
                          drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Class P-1B (asymptomatic) or class
                          P-2 (symptomatic) HIV infection. 2. CD4 count
                          < 100 cells/mm3 if >= 2 years of age OR < 200
                          cells/mm3 if < 2 years of age. 3. Negative
                          blood cultures for MAI and no previous or
                          current disseminated infection due to MAC or
                          other mycobacterial infections. 5. No active
                          opportunistic infection OTHER THAN oral
                          candidiasis. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 100 cells/mm3. (if >=
                          two years old). OR < 200 cells/mm3 (if < two
                          years old). ( 0 - 100 ).
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 5 x ULN.
                          Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 01 Days - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Stable dose of
                          AZT, ddC, ddI, or some combination for at
                          least 4 weeks prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: Concomitant
                          antiretroviral therapy. Allowed: Amikacin or
                          ciprofloxacin if given for <= 14 days.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: 1. Any Phase I
                          antiretroviral agents. 2. Antimycobacterial
                          therapy, including rifampin, isoniazid,
                          clofazimine, ethambutol, cycloserine, and
                          ethionamide.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded:
                          Antimycobacterial therapy, including
                          rifampin, isoniazid, clofazimine, ethambutol,
                          cycloserine, and ethionamide.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Positive tuberculin skin test (PPD > 5 mm).
                          2. Known hypersensitivity to rifabutin,
                          rifampin, or other rifamycins.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0085  Rifabutin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0015  Dideoxycytidine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
TRADE NAME OF SUBSTANCE   Drug 3 Videx
TRADE NAME OF SUBSTANCE   Drug 4 HIVID
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 5, 10, or 15 mg/kg
                          daily. Drug 2: Current stable dose at study
                          entry. Drug 3: Current stable dose at study
                          entry. Drug 4: Current stable dose at study
                          entry
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 5, 10, or 15 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, suspension
SUPPORTING AGENCY         National Cancer Institute.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*PREVENTION & CONTROL
MESH HEADING              Rifabutin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Zalcitabine/*THERAPEUTIC USE
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
CAS REGISTRY NUMBER       72559-06-9 (Rifabutin)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        940419
ENTRY MONTH               9311
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN / USA accrual 931026.
 
68
UNIQUE IDENTIFIER         NIH/00568
PROTOCOL ID NUMBERS       NCI 93 C-21
PROTOCOL TITLE            A Pilot Study of the Safety, Growth, and
                          Immunologic Effects of Recombinant Human
                          Insulin-Like Growth Factor (rhIGF-1) and
                          Recombinant Human Growth Hormone (Nutropin;
                          rhGH) in Children With HIV-1 Infection and
                          Growth Retardation.
VERSION NUMBER & DATE     (931026)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To establish the tolerance and
                          safety of recombinant human insulin-like
                          growth factor (rhIGF-1) and recombinant human
                          growth hormone (rhGH) in conjunction with
                          combination antiretroviral therapy with
                          zidovudine (AZT) and didanosine (ddI) in
                          HIV-infected children who have received prior
                          antiretroviral therapy and experienced growth
                          failure. To provide preliminary data on the
                          effects of rhIGF-1 and rhGH on growth, immune
                          function, and viral burden, in order to
                          define the clinical and laboratory parameters
                          necessary for future efficacy studies.
                          Methodology: Patients are initially placed on
                          antiretroviral therapy with AZT/ddI and
                          observed for 12 weeks. They are then
                          randomized to receive either rhIGF-1 or rhGH
                          for 12 weeks; those patients who experience
                          no adverse effects and who demonstrate
                          benefit may continue on study for an
                          additional 12 weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are initially placed on
                          antiretroviral therapy with AZT/ddI and
                          observed for 12 weeks. They are then
                          randomized to receive either rhIGF-1 or rhGH
                          for 12 weeks; those patients who experience
                          no adverse effects and who demonstrate
                          benefit may continue on study for an
                          additional 12 weeks.
PROTOCOL PHASE            Pilot Study
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940419)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. P-2 class symptomatic HIV
                          infection or a CD4 count that qualifies for
                          antiretroviral therapy. 2. Failure to grow or
                          a decrease in growth velocity. 3. Adequate
                          nutrition, i.e., nutrition that provides at
                          least 50 percent of the caloric RDA for
                          weight. 4. No significant active
                          opportunistic infections requiring specific
                          therapy. 5. Euthyroid status (i.e., normally
                          functioning thyroid). NOTE: Hypothyroid
                          status corrected by adequate treatment as
                          documented by normal TSH, T3, and T4 for 3
                          months is acceptable.)
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Comparative; Drug Tolerance; Pilot Study
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Immunotherapy,
                          Comparative drug therapy, Combination drug
                          therapy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24-36 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. P-2 class symptomatic HIV infection
                          or a CD4 count that qualifies for
                          antiretroviral therapy. 2. Failure to grow or
                          a decrease in growth velocity. 3. Adequate
                          nutrition, i.e., nutrition that provides at
                          least 50 percent of the caloric RDA for
                          weight. 4. No significant active
                          opportunistic infections requiring specific
                          therapy. 5. Euthyroid status (i.e., normally
                          function thyroid). NOTE: Hypothyroid status
                          corrected by adequate treatment as documented
                          by normal TSH, T3, and T4 for 3 months is
                          acceptable.) [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          Asymptomatic patients must have a CD4 count
                          that qualifies for antiretroviral therapy.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 06 Months - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 05 Months. 19 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Corticosteroids
                          within 30 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Interferons
                          or other cytokines.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Diabetes mellitus. 2. Critically ill or
                          clinically unstable.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0131  Insulin-Like Growth Factor
                          I
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0132  Somatrem
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 2 Nutropin
TRADE NAME OF SUBSTANCE   Drug 3 Retrovir
TRADE NAME OF SUBSTANCE   Drug 4 Videx
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 120 mcg/kg daily at
                          8am and 6pm for 12-24 weeks. Drug 2: 40
                          mcg/kg daily for 12-24 weeks. Drug 3: 120
                          mg/m2 q 6 h for 24-36 weeks. Drug 4: 135
                          mg/m2 q 12 h for 24-36 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 120 mcg/kg. Drug 2: 40
                          mcg/kg. Drug 3: 480 mg/m2. Drug 4: 270 mg/m2
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 24 weeks.
SUPPORTING AGENCY         National Cancer Institute.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Adolescence
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Hormones, Synthetic/ADVERSE EFFECTS/
                          THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Insulin-Like Growth Factor I/*ADVERSE EFFECTS/
                          THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Somatomedins/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Somatomedins)
CAS REGISTRY NUMBER       0 (Hormones, Synthetic)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       67763-96-6 (Insulin-Like Growth Factor I)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        940419
ENTRY MONTH               9311
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN / USA accrual 931026.
 
69
UNIQUE IDENTIFIER         NIH/00621
PROTOCOL ID NUMBERS       NCI 93 C-207
PROTOCOL TITLE            Pilot Study for the Treatment of
                          Non-Hodgkin's Lymphoma in Patients With
                          Inherited and Acquired Immunodeficiency
                          Syndromes.
VERSION NUMBER & DATE     (940426)
TRIAL CATEGORY            AIDS-Related Malignancies
TRIAL CATEGORY            Child
GENERAL DESCRIPTION       PURPOSE: To obtain preliminary response,
                          survival, and toxicity data in patients with
                          congenital and acquired immunodeficiency
                          syndromes and non-Hodgkin's lymphoma who are
                          treated with three cycles of chemotherapy
                          (systemic cyclophosphamide/methotrexate and
                          intrathecal cytarabine/methotrexate) plus
                          cytokines (granulocyte-colony stimulating
                          factor), plus antiretroviral therapy
                          (zidovudine and didanosine) if HIV-infected.
                          Methodology: Patients are treated with three
                          cycles of chemotherapy (systemic
                          cyclophosphamide/methotrexate and intrathecal
                          cytarabine/methotrexate) plus cytokines
                          (granulocyte-colony stimulating factor), plus
                          antiretroviral therapy (zidovudine and
                          didanosine) if HIV-infected. Patients with
                          intracerebral lymphoma receive a combination
                          of systemic and radiation therapy. Two
                          additional agents (ifosfamide and cytarabine)
                          will be used in patients who relapse or who
                          have persistent disease at completion of
                          therapy. Patients who fail the initial drug
                          combination will be permitted to receive a
                          second drug combination (three cycles of
                          ifosfamide and cytarabine with intrathecal
                          methotrexate).
GENERAL DESCRIPTION       METHODOLOGY: Patients are treated with three
                          cycles of chemotherapy (systemic
                          cyclophosphamide/methotrexate and intrathecal
                          cytarabine/methotrexate) plus cytokines
                          (granulocyte-colony stimulating factor), plus
                          antiretroviral therapy (zidovudine and
                          didanosine) if HIV-infected. Patients with
                          intracerebral lymphoma receive a combination
                          of systemic and radiation therapy. Two
                          additional agents (ifosfamide and cytarabine)
                          will be used in patients who relapse or who
                          have persistent disease at completion of
                          therapy. Patients who fail the initial drug
                          combination will be permitted to receive a
                          second drug combination (three cycles of
                          ifosfamide and cytarabine with intrathecal
                          methotrexate).
PROTOCOL PHASE            Pilot Study
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940426)
DISEASE STUDIED           Lymphoma, non-Hodgkin's.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Congenital or acquired
                          immunodeficiency syndrome, including HIV
                          infection. 2. Proven B-cell non-Hodgkin's
                          lymphoma of small non-cleaved cell or diffuse
                          large cell type and no overt, serious
                          concurrent infection OR a polyclonal
                          lymphoproliferative process with failure on a
                          trial of alpha interferon/IVIG.
ELIGIBILITY               AIDS. OTHER - immunocompromised.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Drug Combination; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy, Combination
                          modality therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Congenital or acquired
                          immunodeficiency syndrome, including HIV
                          infection. 2. Proven B-cell non-Hodgkin's
                          lymphoma of small non-cleaved cell or diffuse
                          large cell type and no overt, serious
                          concurrent infection OR a polyclonal
                          lymphoproliferative process with failure on a
                          trial of alpha interferon/IVIG. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 03 Months - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed in patients
                          with intracerebral lymphoma: Radiation
                          therapy.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required in patients with a
                          polyclonal lymphoproliferative process
                          superimposed on an immunodeficiency syndrome:
                          Prior non-cytotoxic therapy (i.e., alpha
                          interferon/IVIG).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 19 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Therapy for
                          a new opportunistic infection (may be
                          eligible after infection has resolved or is
                          controlled).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0048  Cyclophosphamide
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0024  Methotrexate
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0038  Cytarabine
SUBSTANCE IDENTIFICATION  Drug 6  DRG-0086  Granulocyte
                          colony-stimulating factor
SUBSTANCE IDENTIFICATION  Drug 7  DRG-0207  Ifosfamide
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 5: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 6: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 7: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 4: Intrathecal and
                          systemic. Drug 5: Intrathecal
SUPPORTING AGENCY         National Cancer Institute.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Combined Modality Therapy
MESH HEADING              Cyclophosphamide/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Cytarabine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Didanosine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Granulocyte Colony-Stimulating Factor/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Ifosfamide/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Immunocompromised Host
MESH HEADING              Infant
MESH HEADING              Lymphoma, Non-Hodgkin's/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Male
MESH HEADING              Methotrexate/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       147-94-4 (Cytarabine)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       3778-73-2 (Ifosfamide)
CAS REGISTRY NUMBER       50-18-0 (Cyclophosphamide)
CAS REGISTRY NUMBER       59-05-2 (Methotrexate)
CAS REGISTRY NUMBER       62683-29-8 (Granulocyte Colony-Stimulating
                          Factor)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        940426
ENTRY MONTH               9404
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN / USA accrual 940426.
 
70
UNIQUE IDENTIFIER         NIH/00566
PROTOCOL ID NUMBERS       NCI 93 C-193
PROTOCOL TITLE            A Phase II Study of Paclitaxel (Taxol)
                          Administered as a Three-Hour Infusion for
                          Patients With HIV Infection and Kaposi's
                          Sarcoma.
VERSION NUMBER & DATE     (931013)
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Saville W
GENERAL DESCRIPTION       PURPOSE: To study paclitaxel (Taxol) as a
                          3-hour infusion administered every 21 days in
                          patients with HIV infection and Kaposi's
                          sarcoma.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (931013)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection. 2. Kaposi's
                          sarcoma. NOTE: Patients with pulmonary
                          Kaposi's sarcoma that causes more than mild
                          symptoms or with other acutely
                          life-threatening lesions are not eligible. 3.
                          Receiving a stable dose of antiretroviral
                          therapy consisting of AZT, ddI, ddC, or
                          stavudine (d4T), either alone or in
                          combination, for at least 1 month prior to
                          study entry.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    MB 324
STUDY DESIGN              Dose Escalating
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 10 - 34 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Kaposi's sarcoma.
                          3. Been receiving a stable dose of
                          antiretroviral therapy for at least 1 month
                          prior to study entry. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl. (Transfusion
                          permitted within 1 month prior to study
                          entry).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 125 units/L.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 125 units/L.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min. /1.73 m2.
                          (if creatinine value not available.)
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. PTT or PT no more than 120 percent
                          of control.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Allowed: Transfusion within
                          1 month prior to study entry.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Stable dose of
                          antiretroviral therapy (AZT, ddI, ddC, d4T)
                          for at least 1 month prior to study entry.
                          Allowed: One prior cytotoxic chemotherapy
                          regimen, excluding interferon and retinoic
                          acid.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hepatic cirrhosis or dysfunction.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 4 weeks
                          prior to study entry: 1. Radiation therapy.
                          2. Intralesional therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: 1. Radiation
                          therapy. 2. Intralesional therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: 1. Cytotoxic
                          chemotherapy. 2. Interferon. 3. Other
                          systemic anti-KS agents. 4. Systemic
                          steroids. Excluded within 24 hours prior to
                          Taxol infusion: 1. ddI. 2. Ketoconazole.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapy. 2. Interferon. 3. Other
                          systemic anti-KS agents. 4. Systemic
                          steroids. 5. ddI (within 24 hours prior to
                          Taxol infusion). 6. Ketoconazole (within 24
                          hours prior to Taxol infusion).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Grade
                          2 peripheral neuropathy. 2. H/O cardiac
                          disease including myocardial infarction,
                          congestive heart failure, angina, and
                          coronary artery disease.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0190  Taxol
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 135 mg/m2 over 3 hr
                          on day 0, 155 mg/m2 on day 21, and then 175
                          mg/m2 on day 42 and q 21 days thereafter
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
SUPPORTING AGENCY         National Cancer Institute Adult Intramural
                          Studies.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Taxol/*THERAPEUTIC USE
CAS REGISTRY NUMBER       33069-62-4 (Taxol)
LAST REVISION DATE        931013
ENTRY MONTH               9310
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Jill Lietzau (301) 496-5489 Contact: Kathy
                          Wyvill (301) 496-8959 OPEN / USA accrual
                          931013.
 
71
UNIQUE IDENTIFIER         NIH/00567
PROTOCOL ID NUMBERS       NCI 93 C-192
PROTOCOL TITLE            A Pilot Study to Evaluate the Safety and
                          Efficacy of the Combination of AZT, ddI, and
                          BI-RG-587 (Nevirapine) in Children With
                          Progressive HIV Disease.
VERSION NUMBER & DATE     (931026)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and efficacy
                          of combination therapy with zidovudine (AZT),
                          didanosine (ddI), and nevirapine in children
                          aged 6 months to 18 years, who have either a
                          persistently elevated or rising p24 antigen
                          level while receiving AZT/ddI. To study the
                          impact of this triple regimen on viral burden
                          in plasma and tissue sites (i.e., lymph
                          nodes), the effect on viral resistance, and
                          the pharmacokinetics of single-dose
                          nevirapine. Methodology: Patients receive
                          nevirapine/AZT/ddI in combination for at
                          least 24 weeks. They remain on their
                          previously established AZT/ddI regimen
                          throughout the study. A lymph node biopsy is
                          required prior to beginning combination
                          therapy and at week 24. Patients are followed
                          monthly during the first 24 weeks and every
                          other month thereafter.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive
                          nevirapine/AZT/ddI in combination for at
                          least 24 weeks. They remain on their
                          previously established AZT/ddI regimen
                          throughout the study. A lymph node biopsy is
                          required prior to beginning combination
                          therapy and at week 24. Patients are followed
                          monthly during the first 24 weeks and every
                          other month thereafter.
PROTOCOL PHASE            Pilot Study
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940419)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. P-2 class symptomatic HIV
                          infection OR asymptomatic HIV infection with
                          an age-corrected absolute CD4 count
                          recommended for initiation of antiretroviral
                          therapy (i.e., 1-11 months - 1750 cells/mm3;
                          12-23 months - 1000 cells/mm3; 24 months to 5
                          years - 750 cells/mm3; >= 6 years - 500
                          cells/mm3). 2. Prior treatment with AZT/ddI
                          for at least 12 weeks according to protocol
                          NCI 91 C-09 (ACTG 176), at one of the
                          following dose levels: AZT 90 mg/m2 every 6
                          hours plus ddI 135 mg/m2 every 12 hours; AZT
                          120 mg/m2 every 6 hours plus ddI 135 or 180
                          mg/m2 every 12 hours; or AZT 180 mg/m2 every
                          6 hours plus ddI 135 mg/m2 every 12 hours. 3.
                          No active opportunistic infection requiring
                          acute intervention. 4. Persistently positive
                          serum p24 antigen > 100 pg/ml after 24 weeks
                          of combination AZT/ddI therapy OR an increase
                          in serum p24 antigen by 50 percent or more
                          after at least 12 weeks of combination
                          AZT/ddI therapy.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Drug Combination; Pilot Study
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Pharmacokinetics, Combination drug therapy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 24
                          weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. P-2 class symptomatic HIV infection
                          OR asymptomatic HIV infection with an
                          age-corrected absolute CD4 count recommended
                          for initiation of antiretroviral therapy. 2.
                          Prior treatment with AZT/ddI for at least 12
                          weeks according to protocol NCI 91 C-09 (ACTG
                          176), at one of the specified dose levels. 3.
                          No active opportunistic infection requiring
                          acute intervention. 4. Persistently positive
                          serum p24 antigen > 100 pg/ml after 24 weeks
                          of combination AZT/ddI therapy OR an increase
                          in serum p24 antigen by 50 percent or more
                          after at least 12 weeks of combination
                          AZT/ddI therapy. 5. Availability of parent or
                          guardian to given informed consent and to be
                          sufficiently reliable to return for the
                          child's follow-up visits. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl. (Recent transfusion
                          acceptable).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          (If P-2 class symptomatic). OR If
                          asymptomatic, then age-corrected CD4 count:
                          one to eleven months - 1750 cells/mm3; twelve
                          to twenty-three months - 1000 cells/mm3;
                          twenty-four months to five years - 750 ce
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 10 x ULN mg/dl. (ULN = upper
                          limit of normal). Children with chronic
                          elevations of known etiology will be enrolled
                          but not evaluated for hepatotoxicity.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 10 x ULN. (If bilirubin value
                          unavailable). Children with chronic
                          elevations of k
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 10 x ULN. (If bilirubin value
                          unavailable). Children with chronic
                          elevations of known etiology will be enrolled
                          but not evaluated for hepatotoxicity.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   OTHER: White blood cells >= 1000 cells/mm3.
                          Neutrophils plus bands >= 750 cells/mm3.
PATIENT AGE               AGE: 06 Months - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Corticosteroids for LIP or an autoimmune
                          process.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 05 Months. 19 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 30 days
                          prior to study entry: Radiation therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 30 days
                          prior to study entry: 1. Immunomodulating
                          agents. 2. Cytolytic agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          condition are excluded: Critically ill or
                          unstable.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0116  Nevirapine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 Videx
TRADE NAME OF SUBSTANCE   Drug 3 BI-RG-587
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 90, 120, or 180
                          mg/m2 q 6 h, according to previously
                          established regimen. Drug 2: 135 mg/m2 q 12
                          h, according to previously established
                          regimen. Drug 3: 120 mg/m2 daily during weeks
                          1 through 4, then 240 mg/mdaily during weeks
                          5 through 24
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 360, 480, or 720 mg/m2.
                          Drug 2: 270 mg/m2. Drug 3: 120 mg/m2 (weeks 1
                          through 4); 240 mg/m2 (weeks 5 throu24)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 24 weeks.
SUPPORTING AGENCY         National Cancer Institute.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Adolescence
MESH HEADING              Antiviral Agents/*ADVERSE EFFECTS/THERAPEUTIC
                          USE
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Didanosine/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Pyridines/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Zidovudine/*ADVERSE EFFECTS/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        940419
ENTRY MONTH               9311
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN / USA accrual 931026.
 
72
UNIQUE IDENTIFIER         NIH/00570
PROTOCOL ID NUMBERS       NCI 93 C-155
PROTOCOL TITLE            Treatment of Thrombocytopenia With
                          Dideoxynucleosides and Anti-Rh Antibodies
                          (Anti-D) in Children With HIV Infection: A
                          Phase II Study.
VERSION NUMBER & DATE     (931118)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To establish the role of combination
                          antiretroviral therapy with zidovudine (AZT)
                          and didanosine (ddI) in the treatment of
                          HIV-associated thrombocytopenia in children
                          and to establish the utility of intravenous
                          anti-Rh antibodies (anti-D) in HIV-infected
                          children with thrombocytopenia unresponsive
                          to antiretroviral therapy. Methodology: In
                          Arm A of the study, patients receive AZT and
                          ddI in combination for at least 6 weeks. In
                          Arm B, anti-D is given plus AZT/ddI (or any
                          other stable antiretroviral therapy),
                          following at least 6 prior weeks of AZT/ddI
                          (or any other stable antiretroviral therapy)
                          during which thrombocytopenia worsened or did
                          not improve. Bone marrow biopsies are
                          performed at study entry and repeated after 6
                          and 12 weeks of treatment.
GENERAL DESCRIPTION       METHODOLOGY: In Arm A of the study, patients
                          receive AZT and ddI in combination for at
                          least 6 weeks. In Arm B, anti-D is given plus
                          AZT/ddI (or any other stable antiretroviral
                          therapy), following at least 6 prior weeks of
                          AZT/ddI (or any other stable antiretroviral
                          therapy) during which thrombocytopenia
                          worsened or did not improve. Bone marrow
                          biopsies are performed at study entry and
                          repeated after 6 and 12 weeks of treatment.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940419)
DISEASE STUDIED           Primary HIV infection / thrombocytopenia.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection. 2. Rhesus
                          positive (Rh+). 3. No obvious cause for
                          thrombocytopenia other than HIV infection. 4.
                          Absence of life-threatening bleeding. 5. No
                          significant active opportunistic infection
                          requiring drug therapy at study entry. Part A
                          - o Platelets < 50000 on two separate days
                          within a 2-week period. o Received no prior
                          antiretroviral therapy OR received prior
                          single-agent therapy (any drug) OR
                          combination therapy with agents other than
                          AZT and ddI. Part B - o Have received prior
                          combination AZT/ddI (or any other stable
                          antiretroviral therapy) for at least 6 weeks
                          and either developed thrombocytopenia or have
                          not had improvement in platelet count to >=
                          30000. o Platelets < 30000 on two separate
                          days within a 1-week period after 6 weeks of
                          treatment with AZT/ddI.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Drug Combination; 2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Immunotherapy,
                          Combination drug therapy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 12
                          weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Rhesus positive
                          (Rh+). 3. No obvious cause for
                          thrombocytopenia other than HIV infection. 4.
                          Absence of life-threatening bleeding. 5.
                          Platelet count < 50000 for Part A and < 30000
                          for Part B. 6. No significant active
                          opportunistic infection at study entry. 7.
                          PART A - Must have received no prior
                          antiretroviral therapy OR received prior
                          single-agent therapy (any drug) OR prior
                          combination therapy with agents other than
                          AZT and ddI. PART B - Have received prior
                          combination AZT/ddI (or any other stable
                          antiretroviral therapy) for at least 6 weeks
                          with developing on continuing
                          thrombocytopenia. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: < 50000 platelets/mm3. (on
                          Part A). < 30000 (on Part B).
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 10 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min. /1.73 m2.
                          (If creatinine value not available).
PATIENT AGE               AGE: 03 Months - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic pancreatitis. 2.
                          History of withdrawal grade toxicity during
                          treatment with AZT and ddI, thrombocytopenia
                          excluded. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 19 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: 1. Radiation
                          therapy within 30 days prior to study entry.
                          2. Bone marrow transplantation within 6
                          months prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 30 days
                          prior to study entry: 1. Immunomodulating
                          agents (interleukin-2, interferons, or other
                          biologic response modifiers). 2. Cytolytic
                          chemotherapeutic agents. Excluded within 14
                          days prior to study entry: 1. G-CSF. 2.
                          Corticosteroids (unless needed for treatment
                          of a condition other than thrombocytopenia).
                          3. Immunoglobulins.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Significant active other infection requiring
                          drug therapy at study entry. 2. Known
                          hemolytic anemia (Part B). 3. Known severe
                          allergic reactions to plasma products (Part
                          B).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0191  Anti-Rh antibodies
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 Anti-D
TRADE NAME OF SUBSTANCE   Drug 3 Videx
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 120 mg/m2 q 6 h for
                          at least 12 weeks. Drug 2: 40 mcg/kg not more
                          often than weekly, for at least 6
                          we(following 6 weeks of combination
                          antiretroviral therapy). Drug 3: 135 mg/m2 q
                          12 h for at least 12 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 480 mg/m2. Drug 3: 270
                          mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 2: Intravenous
SUPPORTING AGENCY         National Cancer Institute.
MESH HEADING              AIDS-Related Complex/COMPLICATIONS/*DRUG
                          THERAPY/IMMUNOLOGY
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          COMPLICATIONS/*DRUG THERAPY/IMMUNOLOGY
MESH HEADING              Adolescence
MESH HEADING              Antibodies/*IMMUNOLOGY
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/COMPLICATIONS/*DRUG THERAPY/
                          IMMUNOLOGY
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Thrombocytopenia/COMPLICATIONS/IMMUNOLOGY/
                          *THERAPY
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antibodies)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        940419
ENTRY MONTH               9311
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Susan Sandelli (301) 402-1391 Contact: (301)
                          402-1387 OPEN / USA accrual 931026.
 
73
UNIQUE IDENTIFIER         NIH/00541
PROTOCOL ID NUMBERS       NCI 92 C-47
PROTOCOL TITLE            A Phase I/II Trial of Amphotericin B Lipid
                          Complex (ABLC) in the Treatment of
                          Hepatosplenic Candidiasis in Children With
                          Neoplastic Diseases.
VERSION NUMBER & DATE     (920421)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
PROTOCOL CHAIRS           CHAIR  Pizzo PA
PROTOCOL CHAIRS           CO-CHAIR  Walsh TJ
GENERAL DESCRIPTION       PURPOSE: To investigate the safety,
                          pharmacokinetics, and antifungal response of
                          three dosing regimens of amphotericin B lipid
                          complex (ABLC) for the treatment of
                          hepatosplenic candidiasis in pediatric
                          patients with neoplastic diseases.
GENERAL DESCRIPTION       RATIONALE: Hepatosplenic candidiasis commonly
                          presents in children receiving aggressive
                          cytotoxic chemotherapy. To improve treatment
                          of this infection, amphotericin B has been
                          formulated into a lipid complex, which
                          permits administration of larger doses with
                          less toxicity.
GENERAL DESCRIPTION       METHODOLOGY: Patients are enrolled in three
                          cohorts of 10 patients each. When eight of
                          ten patients in a given cohort have completed
                          therapy with ABLC, treatment begins for the
                          next cohort at a higher dose for a shorter
                          duration. Patients are evaluated at months 1,
                          2, 3, and 6 following completion of therapy.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940419)
DISEASE STUDIED           Candidiasis, Hepatosplenic.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Underlying neoplastic disease.
                          2. Candida in liver or spleen, proven
                          histopathologically or by culture.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    T92-0001
STUDY DESIGN              Dose Escalating; Open Label; Pharmacokinetic;
                          Pilot Study
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Pharmacokinetics,
                          Drug efficacy, Drug dosing schedule.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients.
PROTOCOL DETAILS          STUDY DURATION: Approximately 18 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Underlying neoplastic disease. 2.
                          Candida in liver or spleen. 3. Central venous
                          catheterization. 4. Consent of parent or
                          guardian. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 7 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 7 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 30 ml/min. /1.73 m2.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3.
PATIENT AGE               AGE: 02 Years - 18 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Blood, blood
                          products, or intravenous lipids (if
                          administered at least 3 hours before or 1
                          hour after ABLC infusions).
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Corticosteroids.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of anaphylaxis attributed to
                          amphotericin B. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 01 Years. 19 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Investigational drugs (other than cytotoxic
                          chemotherapeutic or immunomodulatory agents)
                          within 2 weeks prior to study entry. 2.
                          Amphotericin B within 2 months prior to study
                          entry. (NOTE: Patients who have received < 3
                          mg/kg amphotericin B within the past 2 months
                          are eligible if drug is discontinued at least
                          7 days prior to study entry).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapeutic or immunomodulatory agents.
                          2. Other systemic antifungal agents,
                          including non-liposomal amphotericin B, 5-FC,
                          or fluconazole. 3. Interferon, IL-2, GM-CSF,
                          or isoprinosine. 4. Salicylates, nonsteroidal
                          anti-inflammatory agents, or other compounds
                          known to interfere with prostaglandin
                          synthesis (except if indicated for adverse
                          events).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Any
                          other concomitant condition that would
                          preclude participation.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unavailable for follow-up.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0096  Amphotericin B Lipid
                          Complex
MANUFACTURERS             Drug 1: Bristol-Myers Squibb Company PO Box
                          4000 Princeton, NJ 08534-4000 Contact: Dr Joe
                          Sonk (609) 252-5710.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Cohort 1: 2.5 mg/kg
                          daily for 42 days. Cohort 2: 5.0 mg/kg daily
                          for 21 days. Cohort 3: 7.5 mg/kg daily for 14
                          days. Total cumulative dose for each cohort:
                          105 mg/kg
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 2.5, 5.0, or 7.5 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, 20 ml
                          vials
OTHER TREATMENT INFO.     TREATMENT DURATION: 14, 21, or 42 days.
OTHER TREATMENT INFO.     END POINT: Toxicity, pharmacokinetics,
                          antifungal response.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Deterioration
                          of clinical status. 2. Pregnancy. 3.
                          Development of profound hepatotoxicity or
                          hyperbilirubinemia. 4. Unable to correct
                          prothrombin time to < 3 sec above normal
                          control after two doses of vitamin K. 5.
                          Development of acute severe hemolytic anemia
                          attributable to study drug. 6. Requirement
                          for concomitant treatment with
                          investigational drugs that are not part of
                          neoplastic therapy or supportive care
                          protocol. 7. Serious or intolerable adverse
                          events that preclude further treatment with
                          ABLC.
OTHER TREATMENT INFO.     MODIFICATION: For serum creatinine > 3.0
                          mg/dl: hold study drug until value decreases
                          to 2.5 mg/dl or less, then resume study drug.
                          If serum creatinine does not decrease to
                          acceptable level within 7 days, discontinue
                          study drug permanently.
SUPPORTING AGENCY         National Cancer Institute / Pediatric Branch.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Amphotericin B/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/PHARMACOKINETICS/THERAPEUTIC
                          USE
MESH HEADING              Candidiasis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Opportunistic Infections/COMPLICATIONS/*DRUG
                          THERAPY
CAS REGISTRY NUMBER       1397-89-3 (Amphotericin B)
LAST REVISION DATE        940419
ENTRY MONTH               9307
MARYLAND                  National Cancer Institute / Pediatric Branch
                          9000 Rockville Pike / Bldg 10 Rm 13N240
                          Bethesda, MD 20892 Contact: Dr Thomas Walsh
                          (301) 402-3371 OPEN / USA accrual 920421.
 
74
UNIQUE IDENTIFIER         NIH/00466
PROTOCOL ID NUMBERS       NCI 92 C-228
PROTOCOL TITLE            A Pilot/Phase I Study of the Toxicity,
                          Pharmacokinetics, and Activity of TNP-470
                          Administered to Patients With HIV Infection
                          and Kaposi's Sarcoma.
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Yarchoan R
GENERAL DESCRIPTION       PURPOSE: To determine the toxicity and
                          pharmacokinetic profiles of TNP-470 (formerly
                          AGM 1470) when administered to patients with
                          HIV-associated Kaposi's sarcoma. To obtain
                          preliminary information on the activity of
                          TNP-470 on HIV-associated Kaposi's sarcoma.
                          Methodology: Three to six patients receive
                          TNP-470 at the starting dose IV every other
                          day for 18 weeks. Subsequent cohorts of three
                          to six patients receive TNP-470 at escalating
                          doses until the MTD is determined.
GENERAL DESCRIPTION       METHODOLOGY: Three to six patients receive
                          TNP-470 at the starting dose IV every other
                          day for 18 weeks. Subsequent cohorts of three
                          to six patients receive TNP-470 at escalating
                          doses until the MTD is determined.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930511)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Antibodies to HIV. 2. Kaposi's
                          sarcoma evaluable by noninvasive methods.
                          NOTE: Patients with pulmonary KS, acute
                          life-threatening KS that is responsive to
                          other therapy, or actively bleeding or
                          critically located KS are NOT eligible.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    T92-0041
STUDY DESIGN              Pharmacokinetic; Dose Escalating; Pilot Study
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Pharmacokinetics,
                          Drug efficacy, Maximum tolerated dose (MTD).
PROTOCOL DETAILS          PROJECTED ACCRUAL: 48 patients. (3-6 patients
                          per dose level)
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Antibodies to HIV. 2. Kaposi's
                          sarcoma evaluable by noninvasive methods. 3.
                          Ambulatory status. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.0 mg/dl. or <= 2 x ULN (ULN =
                          upper limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 125 units/L.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min. per 1.73
                          m2 (if creatinine value not available).
PATIENT INCLUSION CRIT.   KARNOFSKY: > 70.
PATIENT INCLUSION CRIT.   OTHER: ANC >= 1000 cells/mm3. APTT or PT <=
                          120 percent of control.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Stable dose of
                          antiretroviral therapy for 1 month prior to
                          study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: Stable dose
                          of antiretroviral therapy.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of substantial noniatrogenic bleeding
                          diasthesis. 2. History of hepatic cirrhosis.
                          3. History of seizures within the past 10
                          years. 4. Body temperature of 39 degrees C or
                          greater within the past 10 days, unless not
                          caused by severe underlying infection. 5.
                          Past history of tumor or malignancy other
                          than KS, with the exception of completely
                          resected basal cell carcinoma of the skin.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Unwilling to refrain from
                          activities that may result in reinfection
                          with HIV.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: 1. Radiation
                          therapy within the past 3 weeks. 2. Blood
                          transfusion within the past month.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Suramin within
                          the past 6 months. 2. Any chemotherapy,
                          interferon, other systemic anti-Kaposi's
                          sarcoma agents or regimens, steroids, or any
                          local treatment (e.g., intralesional
                          injections) within the past 3 weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Anticonvulsants. 2. Steroids. 3. NSAIDS. 4.
                          Anticoagulants. 5. Any other agent that may
                          exacerbate bleeding.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Grade 2 or worse peripheral neuropathy of any
                          cause. 2. Present hepatic dysfunction. 3.
                          Present history of tumor or malignancy other
                          than KS, with the exception of completely
                          resected basal cell carcinoma of the skin. 4.
                          Evidence of active severe or life-threatening
                          infection. 5. Hypersensitivity to TNP-470,
                          fumagillin, cyclodextrin, or other related
                          compounds.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unwilling to be an inpatient.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0148  TNP-470
MANUFACTURERS             Drug 1: National Cancer Institute 9000
                          Rockville Pike Clinical Center Bethesda, MD
                          20892 Contact: Kathy Wyvill (301) 496-8959
                          Contact: Jill Lietzau (301) 496-8959 Contact:
                          Dr James Pluda (301) 496-1196.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 4.6, 9.3, 15.4,
                          23.2, 32.4, 43.1, 57.4, or 76.3 mg/m2 over 1
                          hour every other day for 18 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 4.6 - 76.3 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
SUPPORTING AGENCY         National Cancer Institute Adult Intramural
                          Studies.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antibiotics, Antineoplastic/*ADVERSE EFFECTS/
                          PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Sesquiterpenes/*ADVERSE EFFECTS/
                          PHARMACOKINETICS/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antibiotics, Antineoplastic)
CAS REGISTRY NUMBER       129298-91-5 (AGM 1470)
LAST REVISION DATE        930511
ENTRY MONTH               9210
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Kathy Wyvill (301) 496-8959 Contact: Jill
                          Lietzau (301) 496-8959 Contact: Dr James
                          Pluda (301) 496-1196 OPEN / USA Accrual
                          921015.
 
75
UNIQUE IDENTIFIER         NIH/00465
PROTOCOL ID NUMBERS       NCI 92 C-146
PROTOCOL TITLE            A Pilot Phase I/II Study of the Activity of
                          all-trans-Retinoic Acid (Tretinoin)
                          Administered to Patients With HIV Infections
                          and Kaposi's Sarcoma.
TRIAL CATEGORY            AIDS-Related Malignancies
PROTOCOL CHAIRS           CHAIR  Yarchoan R
GENERAL DESCRIPTION       PURPOSE: To evaluate the activity and
                          tolerance of tretinoin (all-trans-retinoic
                          acid) when administered to patients with
                          HIV-associated Kaposi's sarcoma, both alone
                          and, if necessary, in combination with
                          interferon-alfa.
GENERAL DESCRIPTION       RATIONALE: Current therapies for Kaposi's
                          sarcoma are associated with considerable
                          toxicity, particularly myelosuppression.
                          Recent reports suggest that tretinoin may
                          have activity against HIV-associated Kaposi's
                          sarcoma.
GENERAL DESCRIPTION       METHODOLOGY: Tretinoin is administered PO at
                          40 mg/m2/day in three divided doses every 8
                          hours for 7 days, followed by no tretinoin
                          for the next 7 days. Courses are repeated
                          every 2 weeks for as long as the patient
                          remains on study. If no toxicity develops
                          during the first week of tretinoin
                          administration, doses are escalated by 20
                          mg/m2/day with each course to a maximum dose
                          of 100 mg/m2/day or until the MTD for that
                          patient is reached, whichever is the lower
                          dose. Patients who fail tretinoin therapy
                          after 3 months will be offered additional
                          treatment with tretinoin plus
                          interferon-alfa. All patients must be
                          receiving a stable dose of antiretroviral
                          therapy (either AZT or ddI) for one month
                          prior to study entry, although the doses of
                          these drugs may be reduced or discontinued
                          during the study.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930511)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Serum antibodies to HIV. 2.
                          Kaposi's sarcoma that is evaluable by
                          noninvasive methods, is not acutely
                          life-threatening, and is without pulmonary
                          involvement. Patients with active bleeding or
                          critically located KS lesions may be
                          ineligible for the study, at the discretion
                          of the principal investigator or if such
                          conditions pose an immediate risk to the
                          patient. 3. At least 50 percent of patients
                          should have a CD4 count > 100 cells/mm3.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    Not given
STUDY DESIGN              Dose Escalating; Drug Tolerance; Pilot Study
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug tolerance.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Serum antibodies to HIV. 2. Kaposi's
                          sarcoma that is non-life-threatening and
                          without pulmonary involvement. 3. Life
                          expectancy > 6 months. 4. Ambulatory status.
                          5. At least half of patients should have a
                          CD4 count > 100 cells/mm3. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          (At least 50 percent of patients should have
                          CD4 count > 100 cells/mm3).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.0 mg/dl. or <= 2 x ULN (ULN =
                          upper limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 125 units/L.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min. per 1.73
                          m2. (If creatinine value not available).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          PT or PTT <= 120 percent of control. Fasting
                          triglyceride <= 750 mg/dl or nonfasting
                          triglyceride <= 1000 mg/dl.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT or ddI for 1
                          month prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: AZT or ddI.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of substantial bleeding diathesis
                          (unless completely self-limited). 2. History
                          of hepatic cirrhosis. 3. Past history of
                          tumors or malignancies other than Kaposi's
                          sarcoma, with the exception of completely
                          resected basal cell carcinoma of the skin. 4.
                          Evidence of an underlying severe or
                          life-threatening infection with bacterial,
                          viral, fungal, or protozoal pathogens within
                          14 days prior to study entry. 5. Body
                          temperature of 39 degrees C or greater within
                          10 days prior to study entry, unless
                          apparently not caused by severe underlying
                          infection. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: 1. Radiation
                          therapy within 3 weeks prior to study entry.
                          2. Blood transfusion within the past month.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Suramin within
                          6 months prior to study entry. 2. Cytotoxic
                          chemotherapy, interferon, other systemic
                          anti-Kaposi's sarcoma agents or regimens, or
                          steroids within 3 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Present hepatic dysfunction. 2. Present
                          history of tumors or malignancies other than
                          Kaposi's sarcoma, with the exception of
                          completely resected basal cell carcinoma of
                          the skin. 3. Hypersensitivity to tretinoin or
                          other related compounds.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0147  Tretinoin
MANUFACTURERS             Drug 1: National Cancer Institute 9000
                          Rockville Pike Bethesda, MD 20892 Contact: Dr
                          H C Stevenson (301) 496-8798.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 40 mg/m2/day (with
                          subsequent escalation to a maximum o100
                          mg/m2/day or until the MTD for the patient is
                          reached), in divided doses q 8 hr for 7 days,
                          administered q other week
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 40 mg/m2
SUPPORTING AGENCY         National Cancer Institute Adult Intramural
                          Studies.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Tretinoin/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       302-79-4 (Tretinoin)
LAST REVISION DATE        930511
ENTRY MONTH               9210
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Kathy Wyvill (301) 496-8959 Contact: Jill
                          Lietzau (301) 496-8959 Contact: Dr James
                          Pluda (301) 496-1196 OPEN / USA Accrual
                          921015.
 
76
UNIQUE IDENTIFIER         FDA/00686
PROTOCOL ID NUMBERS       FDA 240A
PROTOCOL TITLE            The Pilot Study of Foscarnet Cream in the
                          Treatment of Mucocutaneous Herpes Simplex
                          Virus Infections in Immunocompromised
                          Patients Unresponsive to Acyclovir Treatment.
VERSION NUMBER & DATE     (941206)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Hardy WD
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To evaluate the clinical
                          activity of foscarnet cream on the index
                          lesion of mucocutaneous herpes simplex virus
                          (HSV) infections in immunocompromised
                          patients previously unresponsive to acyclovir
                          treatment. SECONDARY: To evaluate the
                          clinical activity and virologic activity of
                          foscarnet cream on all treated lesions in
                          this patient population. To evaluate the
                          local tolerance and side effects of treatment
                          with foscarnet cream in this patient
                          population. Methodology: Patients receive
                          topical applications of one percent foscarnet
                          cream five times daily for up to 6 weeks;
                          those who show no evidence of
                          epithelialization of the index lesion after 3
                          or more weeks are removed from study and
                          offered intravenous foscarnet. Patients who
                          show a good response to topical foscarnet
                          cream at the end of 6 weeks may continue
                          receiving treatment at the discretion of the
                          investigator.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive topical
                          applications of one percent foscarnet cream
                          five times daily for up to 6 weeks; those who
                          show no evidence of epithelialization of the
                          index lesion after 3 or more weeks are
                          removed from study and offered intravenous
                          foscarnet. Patients who show a good response
                          to topical foscarnet cream at the end of 6
                          weeks may continue receiving treatment at the
                          discretion of the investigator.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941206)
DISEASE STUDIED           Herpes simplex, mucocutaneous.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection or AIDS by CDC
                          criteria. 2. Virologically confirmed
                          mucocutaneous HSV infection with at least one
                          clinically evaluable HSV lesion of < 25 cm2
                          that can serve as an index lesion. 3. Prior
                          oral (1000 mg/day) or intravenous (5
                          mg/kg/day) acyclovir of 7 or more days
                          duration, with no acceptable clinical effect
                          (i.e., with < 25 percent decrease in HSV
                          lesion size and continued viral shedding).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    92-FT-57
STUDY DESIGN              Multicenter; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 12 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 6 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection or AIDS. 2.
                          Mucocutaneous HSV infection with at least one
                          clinically evaluable lesion. 3. Prior
                          acyclovir without clinical benefit. 4. Life
                          expectancy of at least 3 months. 5. Consent
                          of parent or guardian if less than 18 years
                          of age. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Ganciclovir (provided drug was administered
                          for at least 14 days prior to study entry,
                          and the HSV isolate exhibits resistance
                          against acyclovir). 2. Other medication
                          considered necessary for patient's welfare,
                          at the discretion of the investigator.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          Previous participation in the study. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Intravenous
                          foscarnet within 2 months prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Intravenous foscarnet for current episode of
                          HSV. 2. Acyclovir, interferon, or any
                          investigational drug that might have anti-HSV
                          activity (e.g., 256U87, HPMPC, VBD-araU,
                          trifluridine).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          hypersensitivity to the study drug. 2. Any
                          medical, psychiatric, or other condition that
                          would preclude study compliance. 3. Incapable
                          of self administration of medication or
                          presence of a care provider administering
                          medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0017  Foscarnet sodium
MANUFACTURERS             Drug 1: Astra Pharmaceutical Products
                          Incorporated 50 Otis Street Westborough, MA
                          01581-4500 Contact: Sandra Gulezian (800)
                          388-4148 Contact: (508) 366-1100 X 2309.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 percent cream
                          applied 5 times daily for up to 6 week
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Topical
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 6 weeks.
SUPPORTING AGENCY         Astra Pharmaceutical Products Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Foscarnet/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Herpes Simplex/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       4428-95-9 (Foscarnet)
LAST REVISION DATE        941206
ENTRY MONTH               9412
FLORIDA                   South Miami Hospital 7000 Southwest 62nd
                          Avenue / Suite 650 South Miami, FL 33143
                          Contact: Dr Michael Wohlfeiler (305) 661-1150
                          OPEN 941206.
ILLINOIS                  Dr Thomas Klein 711 West North Avenue / Suite
                          209 Chicago, IL 60610 Contact: Dr Thomas
                          Klein (312) 280-0996 OPEN 941206.
NEW YORK                  Bellevue Hospital Center AIDS Program First
                          Avenue and 27th Street / Room 12 East 12 New
                          York, NY 10016 Contact: Dr Kedernath Javaly
                          (212) 561-3906 OPEN 941206.
RHODE ISLAND              Roger Williams Hospital 825 Chalkstone Avenue
                          Providence, RI 02908 Contact: Dr Gail Skowron
                          (401) 456-2437 Contact: Dr David Friedman
                          OPEN 941206.
 
77
UNIQUE IDENTIFIER         FDA/00685
PROTOCOL ID NUMBERS       FDA 239A
PROTOCOL TITLE            Treatment of Psoriasis Using Acitretin in
                          HIV-Positive Patients.
VERSION NUMBER & DATE     (941006)
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To determine the efficacy of
                          acitretin in the treatment of psoriasis in
                          HIV/AIDS patients.
GENERAL DESCRIPTION       RATIONALE: Etretinate, a retinoid, has proven
                          successful in the treatment of HIV-infected
                          patients with psoriasis, but it has an
                          elimination half-life of 100 days. Acitretin,
                          a metabolite of etretinate, has a much
                          shorter half-life of 2 to 3 days. Acitretin
                          has proven effective in treating psoriasis in
                          patients without HIV infection by reducing
                          skin involvement and clearing of the
                          condition, but it has not been thoroughly
                          evaluated in HIV-infected patients.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive acitretin (0.35
                          mg/kg) daily, with dose increases every 4
                          weeks based on quantitative assessment of the
                          skin using the Psoriasis Area and Severity
                          Index (PASI). Treatment continues for a total
                          of 20 weeks. Patients are followed every 2
                          weeks.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930909)
DISEASE STUDIED           Psoriasis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive. 2. Psoriasis
                          involving at least 10 percent of body
                          surface.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    65-93(2)
STUDY DESIGN              Randomized; Controlled
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Psoriasis
                          involving at least 10 percent of body
                          surface. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 18 Years - 55 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Postmenopausal or
                          permanent sterility including hysterectomy or
                          bilateral tubal ligation.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Any
                          nondermatologic medication.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 56 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Reproductive
                          potential.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0218  Acitretin
TRADE NAME OF SUBSTANCE   Drug 1 Soriatane
MANUFACTURERS             Drug 1: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Beginning dose of
                          0.35 mg/kg/day (maximum 25 mg/day), with
                          possible dose increases q 4 weeks up to 1.4
                          mg/kg/day (max100 mg/day)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 0.35 mg/kg (maximum 25
                          mg), with possible increases q 4weeks up to
                          1.4 mg/kg (maximum 100 mg)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 20 weeks.
SUPPORTING AGENCY         Hoffmann-La Roche, Incorporated.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acitretin/ADMINISTRATION & DOSAGE/
                          *THERAPEUTIC USE
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Psoriasis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       55079-83-9 (Acitretin)
LAST REVISION DATE        930909
ENTRY MONTH               9411
NEW YORK                  Beth Israel Medical Center 1st Avenue at 16th
                          Street New York, NY 10003 Contact: Dr Laura
                          Buccheri (212) 420-2184 OPEN 941121.
 
78
UNIQUE IDENTIFIER         FDA/00642
PROTOCOL ID NUMBERS       FDA 237A
PROTOCOL TITLE            A Phase I Trial to Evaluate the Safety,
                          Tolerance, and Pharmacokinetics of 935U83
                          After Multiple Dosing in Patients With HIV
                          Infection.
VERSION NUMBER & DATE     (940722)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To assess the safety, tolerance, and
                          steady-state pharmacokinetics of multiple
                          oral doses of 935U83 administered to patients
                          with HIV infection. To obtain preliminary
                          evidence of antiretroviral activity of
                          935U83. To prospectively evaluate the
                          emergence of in vitro drug resistance. To
                          determine the effects of 935U83 dosing on
                          CD4+ cell counts. Methodology: Patients (10
                          per dose level) are randomized to receive
                          100, 200, 300, or 500 mg 935U83 every 8 hours
                          for 12 weeks. Five patients at each dose
                          level must complete 4 weeks of treatment
                          without serious toxicity before subsequent
                          patients are entered at the next higher dose.
                          If lack of antiretroviral effect or
                          unacceptable toxicity is demonstrated at a
                          particular dose level, the dose regimens may
                          be adjusted.
GENERAL DESCRIPTION       METHODOLOGY: Patients (10 per dose level) are
                          randomized to receive 100, 200, 300, or 500
                          mg 935U83 every 8 hours for 12 weeks. Five
                          patients at each dose level must complete 4
                          weeks of treatment without serious toxicity
                          before subsequent patients are entered at the
                          next higher dose. If lack of antiretroviral
                          effect or unacceptable toxicity is
                          demonstrated at a particular dose level, the
                          dose regimens may be adjusted.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (931001)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          (confirmed by Western blot), positive HIV
                          blood culture, or positive HIV serum antigen.
                          2. CD4 count 200 - 500 cells/mm3 twice within
                          30 days prior to study entry and at least 7
                          days apart. 3. No history of or current
                          AIDS-defining indicator disease by CDC
                          criteria. 4. No antiretroviral therapy within
                          the past 6 months.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    02
STUDY DESIGN              Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Pharmacokinetics, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 40 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 12
                          weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 7 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count 200 -
                          500 cells/mm3. 3. No history of or current
                          AIDS-defining indicator disease by CDC
                          criteria. 4. No antiretroviral therapy within
                          the past 6 months. 5. Consent of parent or
                          guardian if less than 18 years of age. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 12.0 g/dl. (men); >= 10.5 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 7 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Recommended: PCP
                          prophylaxis for patients whose CD4 counts
                          fall below 200 cells/mm3 or who develop PCP
                          during study participation. Allowed: Acute
                          treatment and secondary prophylaxis for
                          tuberculosis, Mycobacterium avium
                          intracellulare, toxoplasmosis,
                          histoplasmosis, cryptococcosis, disseminated
                          candidiasis, or cytomegalovirus infection.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of chemical, viral, or
                          alcohol-induced clinical hepatitis within the
                          past 3 years. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 7 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current alcohol or illicit
                          drug use that may interfere with study
                          compliance.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within the past 4
                          weeks: Radiation therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within the past 6
                          months: 1. Any antiretroviral therapy. 2. HIV
                          immunotherapeutic vaccine. Excluded within
                          the past 4 weeks: 1. Cytotoxic chemotherapy.
                          2. Immunomodulating agents such as systemic
                          corticosteroids, IL-2, alpha interferon, beta
                          interferon, or gamma interferon.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapy. 2. Other antiretroviral drugs.
                          3. Immunomodulators. 4. Foscarnet. 5. GM-CSF
                          or G-CSF. 6. Erythropoietin.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patient with the following
                          symptoms or conditions are excluded: 1.
                          Current evidence of chronic hepatitis of any
                          etiology. 2. Seropositivity for HBsAg or
                          hepatitis C virus by second generation ELISA.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0215  935U83
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Lisa Behrens (800) 722-9292 X 3633.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100, 200, 300, or
                          500 mg q 8 h for 12 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 300, 600, 900, or 1500
                          mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 weeks.
SUPPORTING AGENCY         Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADVERSE EFFECTS/
                          PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
LAST REVISION DATE        931001
ENTRY MONTH               9408
CALIFORNIA                ViRx Medical Group 1375 Sutter Street Suite
                          407 San Francisco, CA 94102 Contact: Joyce
                          Amann (415) 474-4440 OPEN 940722.
DISTRICT OF COLUMBIA      Georgetown University Medical Center 3800
                          Reservoir Rd NW / Suite 110 Kober-Cogan Bldg
                          Washington, DC 20007 Contact: Keith Dawson
                          (202) 687-7387 OPEN 940722.
FLORIDA                   Dr Goodgame and Hopkins 340 N Maitland Avenue
                          Maitland, FL 32751 Contact: Chuck DeMarzo
                          (407) 647-6000 OPEN 940722.
INDIANA                   Indiana University Hospital 550 North
                          University Boulevard / Room 5550
                          Indianapolis, IN 46202 Contact: Kristin Todd
                          (317) 274-8456 Contact: Dr Kenneth FIfe (317)
                          274-8114 OPEN 940722.
NORTH CAROLINA            Duke University Medical Center Hosp South
                          Room 0207 / Box 3284 Durham, NC 27710
                          Contact: Ken Ship (919) 684-5260 OPEN 940722
                          ACTU: 1601.
OHIO                      University of Cincinnati Medical Center /
                          Holmes Division Eden and Bethesda Avenues
                          Cincinnati, OH 45267 Contact: Jill Leonard
                          (513) 558-8373 OPEN 940722.
PENNSYLVANIA              University of Pittsburgh / School of Medicine
                          3515 Fifth Avenue Pittsburgh, PA 15261
                          Contact: Rosella Rosener (412) 647-8125 OPEN
                          940722.
 
79
UNIQUE IDENTIFIER         FDA/00649
PROTOCOL ID NUMBERS       FDA 236C
PROTOCOL TITLE            An Open-Label Extension Study of Maintenance
                          Therapy in HIV-Positive Subjects With
                          Fluconazole-Refractory Oropharyngeal
                          Candidiasis Who Have Responded to
                          Itraconazole Oral Solution.
VERSION NUMBER & DATE     (940819)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To provide maintenance treatment
                          with itraconazole solution for patients who
                          were clinical responders in the ITR-USA-94
                          protocol, even if they subsequently relapsed.
                          Methodology: Patients who responded to
                          therapy on protocol FDA 236B receive
                          maintenance with itraconazole oral solution
                          for up to 6 months.
GENERAL DESCRIPTION       METHODOLOGY: Patients who responded to
                          therapy on protocol FDA 236B receive
                          maintenance with itraconazole oral solution
                          for up to 6 months.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940816)
DISEASE STUDIED           Candidiasis, oropharyngeal.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Met criteria for clinical
                          response on protocol FDA 236B with no
                          residual visible lesion of oropharygeal
                          candidiasis upon completion of that study. OR
                          2. Initial response on protocol FDA 236B with
                          subsequent relapse and retreatment with
                          itraconazole solution or other therapies.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    ITR-USA-107
STUDY DESIGN              Open Label; Nonrandomized
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 6 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Met criteria for clinical response
                          on protocol FDA 236B with no residual visible
                          lesion of oropharygeal candidiasis upon
                          completion of that study OR had initial
                          response on protocol FDA 236B with subsequent
                          relapse and retreatment with itraconazole
                          solution or other therapies. 2. Life
                          expectancy of at least 3 months. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 7.5 x ULN.
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Previously documented disseminated
                          candidiasis. 2. Previous clinically
                          significant adverse event during treatment
                          with itraconazole oral solution, unless
                          clearly attributable to an intercurrent
                          illness or condition. 3. History of
                          significant hepatic abnormalities or clinical
                          evidence of significant hepatic disease
                          within 2 months prior to study entry. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Any
                          investigational drug (other than itraconazole
                          solution) within 1 month prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Rifampin.
                          2. Rifabutin. 3. Phenobarbital. 4. Phenytoin.
                          5. Carbamazepine. 6. Terfenadine. 7.
                          Astemizole. 8. Systemic antifungals.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Underlying clinical condition that would
                          preclude completion of study or place subject
                          at significant risk. 2. Judged unreliable
                          with respect to physician's directives.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0044  Itraconazole
TRADE NAME OF SUBSTANCE   Drug 1 Sporanox
MANUFACTURERS             Drug 1: Janssen Research Foundation 1125
                          Trenton-Harbourton Road Titusville, NJ
                          08560-0200 Contact: Unspecified (908)
                          730-3183.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Administered for up
                          to 6 months
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, solution
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 6 months.
SUPPORTING AGENCY         Janssen Research Foundation.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Candidiasis, Oral/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Itraconazole/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       84625-61-6 (Itraconazole)
LAST REVISION DATE        940816
ENTRY MONTH               9408
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 940819.
 
80
UNIQUE IDENTIFIER         FDA/00638
PROTOCOL ID NUMBERS       FDA 236B
PROTOCOL TITLE            An Open Study of the Effect of Itraconazole
                          Oral Solution for the Treatment of
                          Fluconazole Refractory Oropharyngeal
                          Candidiasis in HIV-Positive Subjects.
VERSION NUMBER & DATE     (940815)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To assess the efficacy and safety of
                          itraconazole oral solution (100 mg twice
                          daily) in HIV-seropositive patients with
                          oropharyngeal candidiasis that is refractory
                          to fluconazole. Methodology: Patients receive
                          itraconazole oral solution twice daily. Per
                          08/15/94 amendment, patients with complete
                          resolution of oropharyngeal candidiasis
                          lesions upon completion of treatment are
                          eligible for maintenance treatment on
                          protocol FDA 236C. Patients who decline
                          maintenance are followed for 6 weeks.
                          Patients who relapse during follow-up are
                          re-treated for 14-28 days; if lesions clear,
                          patients may enter the maintenance protocol.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive itraconazole
                          oral solution twice daily. Per 08/15/94
                          amendment, patients with complete resolution
                          of oropharyngeal candidiasis lesions upon
                          completion of treatment are eligible for
                          maintenance treatment on protocol FDA 236C.
                          Patients who decline maintenance are followed
                          for 6 weeks. Patients who relapse during
                          follow-up are re-treated for 14-28 days; if
                          lesions clear, patients may enter the
                          maintenance protocol.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940621)
DISEASE STUDIED           Candidiasis, oropharyngeal.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV antibody seropositive or
                          diagnosis of AIDS. 2. Oropharyngeal
                          candidiasis characterized by white patches on
                          oral mucosal surfaces or typcial erythematous
                          lesions on oral mucosal surfaces, and
                          confirmed by histologic exam and culture. 3.
                          Failed fluconazole treatment within the past
                          14 days (minimum 200 mg daily for 2 weeks or
                          more). 4. NO symptoms of esophageal
                          candidiasis (e.g., dysphagia) unless
                          endoscopic exam of esophagus was performed
                          and fungal esophagitis was not present. 5. NO
                          prior disseminated candidiasis.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    ITR-USA-94
STUDY DESIGN              Open Label
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV antibody seropositivity or
                          diagnosis of AIDS. 2. Confirmed oropharyngeal
                          candidiasis. 3. Failed fluconazole treatment
                          within the past 14 days. 4. Life expectancy
                          of at least 3 months. 5. NO symptoms of
                          esophageal candidiasis (e.g., dysphagia)
                          unless endoscopic exam of esophagus was
                          performed and fungal esophagitis was not
                          present. 5. NO prior disseminated
                          candidiasis. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 7.5 x ULN.
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of hypersensitivity to imidazole or
                          azole compounds. 2. Clinical evidence of
                          significant hepatic disease within the past 2
                          months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Investigational
                          drugs within 1 month prior to study entry
                          (approved expanded access drugs are
                          permitted).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Investigational drugs (approved expanded
                          access drugs are permitted). 2. Rifampin. 3.
                          Rifabutin. 4. Phenobarbital. 5. Phenytoin. 6.
                          Carbamazepine. 7. Terfenadine. 8. Astemizole.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Underlying clinical condition that precludes
                          study completion or places the patient at
                          significant risk. 2. Considered unreliable
                          about following physician's directives.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0044  Itraconazole
MANUFACTURERS             Drug 1: Janssen Research Foundation 1125
                          Trenton-Harbourton Road Titusville, NJ
                          08560-0200 Contact: Unspecified (908)
                          730-3183.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 mg twice daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, solution
SUPPORTING AGENCY         Janssen Research Foundation.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Candidiasis, Oral/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Itraconazole/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       84625-61-6 (Itraconazole)
LAST REVISION DATE        940621
ENTRY MONTH               9407
ALABAMA                   University of Alabama at Birmingham 980 20th
                          St South Room 245B Birmingham, AL 35294
                          Contact: Michael S Saag (205) 854-3583 OPEN
                          940607.
ARKANSAS                  University of AR for Medical Sciences 4301
                          West Markham Street Mail Slot 639 Little
                          Rock, AR 72205 Contact: Robert W Bradsher Jr
                          (501) 686-5585 OPEN 940607.
CALIFORNIA                Dr W Jeffrey Fessel 2200 OFarrel San
                          Francisco, CA 94115 Contact: Dr W Jeffrey
                          Fessel (415) 202-3485 OPEN 940607.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue
                          Suite 235 Berkeley, CA 94705 Contact: Nancy
                          Orcutt (510) 204-1291 OPEN 940607.
DISTRICT OF COLUMBIA      Dr Douglas Ward 1737 20th Street NW
                          Washington, DC 20009 Contact: Dr Douglas Ward
                          (202) 745-0201 OPEN 940607.
DISTRICT OF COLUMBIA      The George Washington Univ Med Ctr / Div of
                          Infect Diseases 2150 Pennsylvania Avenue NW /
                          Suite 5-403 Washington, DC 20037 Contact: Dr
                          Carmelita Tuazon (202) 994-4716 Contact:
                          (202) 994-4179 OPEN 940607.
DISTRICT OF COLUMBIA      Veterans Administration Medical Center Infect
                          Disease Sect 50 Irving Street NW Washington,
                          DC 20422 Contact: Dr Virginia Kan (202)
                          745-8301 OPEN 940607.
INDIANA                   Infectious Disease Research Clinic / Indiana
                          Univ Hospital 550 North University Blvd Room
                          5550 Indianapolis, IN 46202 Contact: Dr
                          Mitchell Goldman (317) 630-6262 OPEN 940607.
MARYLAND                  National Institute of Allergy & Infectious
                          Diseases Bldg 10 Rm 11C304 Bethesda, MD 20892
                          Contact: Dr Antonia Geber (301) 496-1238 OPEN
                          940607.
MICHIGAN                  Veterans Administration Medical Center Inf
                          Diseases Sect 2215 Fuller Road Ann Arbor, MI
                          48105 Contact: Dr Carol Ann Kauffman (313)
                          761-7984 OPEN 940607.
MICHIGAN                  Wayne State University / Harper Hospital 4160
                          John R Suite 202 Harper Hospital Detroit, MI
                          48201 Contact: Dr Jose Vazquez (313) 745-0457
                          OPEN 940607.
MISSOURI                  Washington University Clinical Trials Unit
                          4511 Forest Park Suite 304 St Louis, MO 63108
                          Contact: William G Powderly (314) 454-0058
                          OPEN 940607.
OHIO                      Ohio State University Division of Infectious
                          Disease 410 W 10th Avenue N-1135 Doan Hall
                          Columbus, OH 43210 Contact: Dr Susan L
                          Koletar (614) 293-8745 OPEN 940607.
OKLAHOMA                  Veterans Administration Medical Center 921
                          Northeast 13th Street 111C Oklahoma City, OK
                          73104 Contact: Dr Ronald Greenfield (405)
                          270-0501 OPEN 940607.
PENNSYLVANIA              Pennsylvania Hospital 822 Pine Street Suite
                          3a Philadelphia, PA 19107 Contact: John J
                          Stern (215) 925-8010 OPEN 940607.
 
81
UNIQUE IDENTIFIER         FDA/00637
PROTOCOL ID NUMBERS       FDA 236A
PROTOCOL TITLE            Randomized, Controlled, Double-Blind Study of
                          Itraconazole Oral Solution Versus Fluconazole
                          Tablets for the Treatment of Esophageal
                          Candidiasis.
VERSION NUMBER & DATE     (940621)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and efficacy
                          of itraconazole oral solution (100-200 mg
                          daily) versus fluconazole tablets (100-200 mg
                          daily) for the treatment of esophageal
                          candidiasis in immunocompromised patients.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940607)
DISEASE STUDIED           Candidiasis, esophageal.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Esophageal candidiasis
                          characterized by dysphagia, odynophagia,
                          retrosternal/oropharyngeal discomfort,
                          confirmed by endoscopy. 2. Histological
                          evidence of Candida spp. at baseline with
                          confirmation by positive mycological culture.
                          3. HIV infection or other predisposing risk
                          factor, such as antibiotic, corticosteroid,
                          or radiation therapy, or myelosuppression.
ELIGIBILITY               AIDS. OTHER - immunocompromised.
OTHER PROTOCOL NUMBERS    ITR-USA-12
STUDY DESIGN              Controlled; Randomized; Double-Blind
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Comparative drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Esophageal candidiasis. 2.
                          Histological evidence of Candida spp. at
                          baseline with confirmation by positive
                          mycological culture. 3. HIV infection or
                          other predisposing risk factor. 4. Life
                          expectancy of at least 2 months. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of significant hepatic abnormalities
                          or clinical evidence of hepatic disease
                          within 2 months prior to study entry. 2.
                          History of hypersensitivity to imidazole or
                          azole compounds. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Other orally
                          administered antifungal therapy within 3 days
                          prior to study entry. 2. Any investigational
                          drug within 1 month prior to study entry
                          (expanded access drugs are allowed).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Rifampin.
                          2. Rifabutin. 3. Phenobarbital. 4. Phenytoin.
                          5. Carbamazepine. 6. Terfenadine. 7.
                          Astemizole. 8. H2 blockers. 9. Continual
                          antacids. 10. Any investigational drug
                          (expanded access drugs are allowed).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancies of the head or neck, if the
                          treatment or disease will interfere with
                          response assessment. 2. Evidence of systemic
                          fungal infection. 3. Underlying clinical
                          condition that would preclude study
                          completion. 4. Judged to be unreliable in
                          regard to following physician's directives.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0044  Itraconazole
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0005  Fluconazole
TRADE NAME OF SUBSTANCE   Drug 1 Sporanox
MANUFACTURERS             Drug 1: Janssen Research Foundation 1125
                          Trenton-Harbourton Road / PO Box 200
                          Titusville, NJ 08560-0200 Contact:
                          Unspecified (908) 730-3139.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100-200 mg once
                          daily for 3-8 weeks. Drug 2: 100-200 mg once
                          daily for 3-8 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 100-200 mg. Drug 2:
                          100-200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, solution. Drug
                          2: Oral, tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 3 - 8 weeks.
SUPPORTING AGENCY         Janssen Research Foundation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Candidiasis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Fluconazole/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Immunocompromised Host
MESH HEADING              Itraconazole/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       84625-61-6 (Itraconazole)
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        940607
ENTRY MONTH               9406
ARIZONA                   Dr Eskild A Petersen 1501 N Campbell Avenue /
                          Section of Infectious Diseases Tucson, AZ
                          85724 Contact: Dr Eskild A Petersen (602)
                          626-5184 OPEN 940607.
CALIFORNIA                Los Angeles - USC Medical Center / GI and
                          Liver Disease 1200 North State Street / Room
                          12-137 Los Angeles, CA 90033 Contact:
                          Francisco Garcia (213) 226-6939 Contact: Dr
                          Loren Laine (213) 226-7994 Contact: (213)
                          226-7995 OPEN 940607.
CALIFORNIA                UCSD Medical Center 200 W Arbor San Diego, CA
                          92103 Contact: Dr Robert H Goldklang (619)
                          543-3252 OPEN 940607.
DISTRICT OF COLUMBIA      The George Washington Univ Med Ctr / Div of
                          Infect Diseases 2150 Pennsylvania Avenue NW /
                          Suite 5-403 Washington, DC 20037 Contact: Dr
                          Carmelita Tuazon (202) 994-4716 Contact:
                          (202) 994-4179 OPEN 940607.
GEORGIA                   Emory University School of Medicine / GI
                          Division 69 Butler Street SE Atlanta, GA
                          30303 Contact: Lorraine Alexander (404)
                          616-4436 Contact: Dr C Mel Wilcox (404)
                          616-4435 Contact: Fax (404) 522-0404 OPEN
                          940607.
ILLINOIS                  Rush Medical Center 600 South Paulina / Suite
                          143 AcFac Chicago, IL 60612 Contact: Dr John
                          C Pottage Jr (312) 942-5865 OPEN 940607.
MARYLAND                  Johns Hopkins University School of Medicine
                          1830 E Monument Street Suite 7401 Baltimore,
                          MD 21205 Contact: Dr Joel Gallant (410)
                          955-1754 OPEN 940607.
MICHIGAN                  Wayne State University c/o Harper Hospital /
                          3990 John R Detroit, MI 48201 Contact: Dr
                          Ravi Dhar (313) 745-7521 OPEN 940607.
MISSOURI                  University of Missouri - Kansas City 2411
                          Holmes Kansas City, MO 64108 Contact: Dr
                          Stuart Chen (816) 556-3768 OPEN 940607.
MISSOURI                  Dr David S McKinsey 2316 East Meyer Blvd
                          Kansas City, MO 64132 Contact: Dr David S
                          McKinsey (816) 276-4038 OPEN 940607.
NORTH CAROLINA            Bowman Gray School of Medicine Medical Center
                          Boulevard Winston Salem, NC 27157 Contact: Dr
                          P Samuel Pegram (910) 716-4246 OPEN 940607.
NORTH CAROLINA            University of No Carolina / Department of
                          Medicine CB #7080 Burnett Womack Chapel Hill,
                          NC 27514 Contact: Dr Eugene Bozymski (919)
                          966-2511 OPEN 940607.
NEW YORK                  Dr Douglas Dieterich 345 East 37th Street
                          Suite 204 New York, NY 10016 Contact:
                          Kathleen Farrell (212) 263-6485 Contact: Dr
                          Douglas Dieterich (212) 986-3330 OPEN 940607.
NEW YORK                  Montefiore Medical Center 111 E 210th Street
                          Bronx, NY 10467 Contact: Dr Larry Brandt
                          (718) 920-4476 Contact: Dr Aaron Tokayer
                          (718) 920-4476 OPEN 940607.
NEW YORK                  Erie County Medical Center 462 Grider Street
                          Buffalo, NY 14215 Contact: Dr Ross G Hewitt
                          (716) 898-4119 OPEN 090607.
OHIO                      Division of Infectious Disease / ACTU 2061
                          Cornell Road Room 120 Foley Building
                          Cleveland, OH 44106 Contact: Dr John Carey
                          (216) 844-8786 OPEN 940607.
 
82
UNIQUE IDENTIFIER         FDA/00636
PROTOCOL ID NUMBERS       FDA 235B
PROTOCOL TITLE            Randomized Study Comparing Itraconazole to
                          Placebo in the Prevention of Histoplasmosis
                          in Patients With Human Immunodeficiency Virus
                          Infection.
VERSION NUMBER & DATE     (940621)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To assess the safety and efficacy of
                          itraconazole (200 mg daily) versus placebo
                          for prevention of histoplasmosis in
                          HIV-infected patients with CD4 counts < 150
                          cells/mm3 who reside where histoplasmosis is
                          endemic. To assess the safety and efficacy of
                          itraconazole for preventing other
                          debilitating fungal infections, such as
                          cryptococcosis, aspergillosis, recalcitrant
                          oropharyngeal or vaginal candidiasis, and
                          recurrent esophageal candidiasis.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940607)
DISEASE STUDIED           Histoplasmosis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA or
                          Western blot. 2. Residing in an area endemic
                          for H. capsulatum. 3. Absolute CD4 count <
                          150 cells/mm3. 4. No current or past active
                          histoplasmosis. 5. No other active fungal
                          infection.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    MSG 28. ITR-USA-73
STUDY DESIGN              Randomized; Comparative
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Drug prophylaxis.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 7 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Residence in an
                          area endemic for H. capsulatum. 3. Absolute
                          CD4 count < 150 cells/mm3. 4. No current or
                          past active histoplasmosis. 5. No other
                          active fungal infection. 6. Life expectancy
                          of at least 1 year. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 150 cells/mm3. ( 0 -
                          100 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of intolerance to imidazole or azole
                          compounds. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 1 month
                          prior to study entry: Investigational drugs
                          (expanded access drugs are acceptable).
                          Excluded within 15 days prior to study entry:
                          1. Rifampin. 2. Rifabutin. 3. Terfenadine. 4.
                          Astemizole. 5. Phenobarbital. 6. Phenytoin.
                          7. Carbamazepine.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Systemically-active antifungals. 2.
                          Investigational drugs (expanded access drugs
                          are acceptable). 3. Rifampin. 4. Rifabutin.
                          5. Terfenadine. 6. Astemizole. 7.
                          Phenobarbital. 8. Phenytoin. 9.
                          Carbamazepine. 10. H2 blockers. 11.
                          Omeprazole. 12. Continual antacids.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Life-threatening infection or malignancy
                          other than cutaneous Kaposi's sarcoma. 2.
                          Inability to take oral medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0044  Itraconazole
TRADE NAME OF SUBSTANCE   Drug 1 Sporanox
MANUFACTURERS             Drug 1: Janssen Research Foundation 1125
                          Trenton-Harbourton Road / PO Box 200
                          Titusville, NJ 08560-0200 Contact:
                          Unspecified (908) 730-3139.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or placebo)
                          daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
SUPPORTING AGENCY         Janssen Research Foundation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Histoplasmosis/COMPLICATIONS/*PREVENTION &
                          CONTROL
MESH HEADING              Human
MESH HEADING              Itraconazole/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       84625-61-6 (Itraconazole)
LAST REVISION DATE        940607
ENTRY MONTH               9406
INDIANA                   Infectious Disease Research Clinic 550 North
                          University Blvd Room 5550 Indianapolis, IN
                          46202 Contact: Dr L Joseph Wheat (317)
                          630-6262 OPEN 940607.
INDIANA                   Infectious Diseases of Indianapolis 10610 N
                          Pennsylvania / Suite A Indianapolis, IN 46280
                          Contact: Dr Joseph Fraiz (317) 587-2300
                          Contact: Dr Thomas Slama (317) 587-2300 OPEN
                          940607.
MISSOURI                  University of Missouri School of Medicine -
                          Kansas City 2411 Holmes / Red 4 Unit Kansas
                          City, MO 64108 Contact: Dr David Bamberger
                          (816) 276-1940 OPEN 940607.
MISSOURI                  Infectious Disease Association of Kansas City
                          2316 E Meyer Street Kansas City, MO 64132
                          Contact: Dr David McKinsey (816) 276-4038
                          OPEN 940607.
 
83
UNIQUE IDENTIFIER         FDA/00631
PROTOCOL ID NUMBERS       FDA 234D
PROTOCOL TITLE            A Pilot Study of OPC-8212 (Vesnarinone) in
                          Persons With AIDS-Related Kaposi's Sarcoma.
VERSION NUMBER & DATE     (940517)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To examine the safety and efficacy
                          of 60 or 90 mg vesnarinone in patients with
                          AIDS-related Kaposi's sarcoma. Methodology:
                          Twenty-eight patients (14 per cohort) receive
                          daily vesnarinone at one of two doses. At
                          least seven patients at the lower dose must
                          have completed 2 weeks of therapy before
                          subsequent patients are entered at the higher
                          dose. Patients who successfully complete 16
                          weeks of treatment may receive maintenance
                          therapy for the duration of the study
                          (approximately 12-18 months).
GENERAL DESCRIPTION       METHODOLOGY: Twenty-eight patients (14 per
                          cohort) receive daily vesnarinone at one of
                          two doses. At least seven patients at the
                          lower dose must have completed 2 weeks of
                          therapy before subsequent patients are
                          entered at the higher dose. Patients who
                          successfully complete 16 weeks of treatment
                          may receive maintenance therapy for the
                          duration of the study (approximately 12-18
                          months).
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940401)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by a secondary test. 2.
                          Biopsy-proven Kaposi's sarcoma. 3. No current
                          constitutional signs of HIV disease. 4. No
                          active AIDS-defining opportunistic infection,
                          malignancy (other than Kaposi's sarcoma), or
                          other medical condition by CDC criteria.
                          NOTE: For each cohort, seven patients must
                          have CD4 count < 200 cells/mm3 and seven
                          patients must have CD4 count > 200 cells/mm3.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    22-93-254
STUDY DESIGN              Open Label; Dose Escalating
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 28 patients. (14 patients
                          in each of 2 cohorts)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 - 18 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2.
                          Kaposi's sarcoma. 3. No current
                          constitutional signs of HIV disease or
                          AIDS-defining conditions other than Kaposi's
                          sarcoma. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 mg/dl. (except for patients
                          with Gilbert's disease.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. TSH < 1.5 x ULN. Electrolytes
                          within normal limits.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Limited
                          electron-beam radiation therapy to non-marker
                          lesions for treatment of Kaposi's sarcoma.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii,
                          candida, and mycobacteria. 2. Acyclovir as
                          acute treatment for herpes outbreaks.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior history of significant cardiac disease
                          or anomaly. 2. History of agranulocytosis or
                          severe grade 3 drug-induced neutropenia or
                          documented abnormalities in granulocyte
                          function. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active illicit drug abuse
                          (specifically cocaine, amyl nitrate, heroin,
                          or other cardioactive agents).
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 30 days
                          prior to study entry: Blood or cellular blood
                          product.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy including electron beam irradiation
                          (other than limited electron-beam radiation
                          to non-marker lesions for treatment of
                          Kaposi's sarcoma).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. AZT within 14
                          days prior to study entry. 2. Acyclovir as
                          prophylaxis for herpes within 48 hours prior
                          to study entry. Excluded within 30 days prior
                          to study entry: 1. Interferon. 2. Biologic
                          response modifiers. 3. Cytotoxic
                          chemotherapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral agents, including ddI, ddC,
                          AZT, and d4T. 2. Immunosuppressive agents. 3.
                          Investigational HIV drugs/therapies including
                          vaccines (except those on treatment IND for
                          approved indications). 4. Other anti-Kaposi's
                          sarcoma/HIV drugs. 5. Corticosteroids (other
                          than topical). 6. Biologic response
                          modifiers. 7. Megestrol acetate. 8. Agents
                          known to cause neutropenia. 9.
                          Trimethoprim/sulfamethoxazole in excess of
                          160 mg trimethoprim and 800 mg
                          sulfamethoxazole thrice weekly. 10. Cytotoxic
                          chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active malignancy other than Kaposi's
                          sarcoma, cutaneous basal cell carcinoma, or
                          in situ carcinoma of the cervix. 2. Current
                          significant cardiac disease or anomaly
                          (including prolonged QTC on EKG). 3. Abnormal
                          cardio-thoracic ratio on chest x-ray.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0210  Vesnarinone
TRADE NAME OF SUBSTANCE   Drug 1 OPC-8212
MANUFACTURERS             Drug 1: Otsuka America Pharmaceutical Inc
                          2440 Research Blvd Rockville, MD 20874
                          Contact: Dr Robert G Petit (301) 990-0030.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 60 or 90 mg/day for
                          up to 18 months
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 60 or 90 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 - 18 months.
SUPPORTING AGENCY         Otsuka America Pharmaceutical Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       81840-15-5 (OPC 8212)
LAST REVISION DATE        940401
ENTRY MONTH               9405
CALIFORNIA                UCLA School of Medicine / Division of
                          Hematology / Oncology Room 60 051 CHS Los
                          Angeles, CA 90012-1973 Contact: Dr Ronald
                          Mitsuyasu (310) 206-6414 OPEN 940401.
ILLINOIS                  Northwestern University Medical School 233
                          East Erie Street / Suite 700 Chicago, IL
                          60611 Contact: Dr J Hayden von Roenn (312)
                          908-9412 OPEN 940401.
 
84
UNIQUE IDENTIFIER         FDA/00630
PROTOCOL ID NUMBERS       FDA 234C
PROTOCOL TITLE            A Long-Term, Follow-On Safety Study of Four
                          Doses of OPC-8212 (Vesnarinone) in
                          HIV-Infected Persons.
VERSION NUMBER & DATE     (940517)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To examine the continued safety and
                          tolerability of four doses of vesnarinone in
                          HIV-infected patients who have completed a
                          short-term study (less than 12 months on
                          continuous treatment) of the drug.
                          Methodology: Patients who have completed a
                          limited duration study (less than 12 months
                          of continuous treatment) of vesnarinone on
                          protocols FDA 234A or FDA 234B and who have
                          no current signs or symptoms of AIDS-defining
                          illnesses may roll over to this study and
                          continue receiving their regimen of
                          vesnarinone for 12 months beyond their
                          original participation.
GENERAL DESCRIPTION       METHODOLOGY: Patients who have completed a
                          limited duration study (less than 12 months
                          of continuous treatment) of vesnarinone on
                          protocols FDA 234A or FDA 234B and who have
                          no current signs or symptoms of AIDS-defining
                          illnesses may roll over to this study and
                          continue receiving their regimen of
                          vesnarinone for 12 months beyond their
                          original participation.
PROTOCOL PHASE            OTHER
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940517)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients meet the following criteria:
                          Successful completion of short-term therapy
                          with vesnarinone on FDA 234A or FDA 234B.
ELIGIBILITY               ASYM. AIDS.
OTHER PROTOCOL NUMBERS    22-93-253
STUDY DESIGN              Open Label; Dose Comparison; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: OPEN patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients meet the
                          following criteria: Successful completion of
                          short-term therapy with vesnarinone on FDA
                          234A or FDA 234B. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl. (men); >= 8.0
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: Criteria met for protocol FDA
                          234A or FDA 234B.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          Criteria met for protocol FDA 234A or FDA
                          234B.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: Criteria met for protocol FDA 234A
                          or FDA 234B.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils: Criteria met for
                          protocol FDA 234A or FDA 234B. Alkaline
                          phosphatase < 5 x ULN. TSH < 1.5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii,
                          candida, and mycobacteria. 2. Acyclovir for
                          acute treatment of herpes.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Poor compliance (less than 80 percent of drug
                          taken) on the Phase I protocol (FDA 234A or
                          FDA 234B). 2. Missed more than one clinic
                          visit on the Phase I protocol. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active illicit drug abuse.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Acyclovir as
                          prophylaxis for herpes within 48 hours prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral agents, including ddI, ddC,
                          AZT, and d4T. 2. Immunosuppressive agents. 3.
                          Investigational HIV drugs/therapies including
                          vaccines. 4. Interferon or other
                          immunomodulating agents. 5. Corticosteroids
                          (other than topical). 6. Megestrol acetate.
                          7. Agents known to cause neutropenia. 8.
                          Ganciclovir. 9. Cytotoxic chemotherapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0210  Vesnarinone
TRADE NAME OF SUBSTANCE   Drug 1 OPC-8212
MANUFACTURERS             Drug 1: Otsuka America Pharmaceutical Inc
                          2440 Research Blvd Rockville, MD 20874
                          Contact: Dr Robert G Petit (301) 990-0030.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 30, 60, 90, or 120
                          mg/day for 12 months
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 30, 60, 90, or 120 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, Tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 months.
SUPPORTING AGENCY         Otsuka America Pharmaceutical Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       81840-15-5 (OPC 8212)
LAST REVISION DATE        940517
ENTRY MONTH               9405
CALIFORNIA                UCLA School of Medicine / Division of
                          Hematology / Oncology Room 60 051 CHS Los
                          Angeles, CA 90012-1973 Contact: Dr Ronald
                          Mitsuyasu (310) 206-6414 OPEN 940517.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon / Suite 130 Atlanta, GA 30308
                          Contact: Dr Melanie Thompson (404) 876-2317
                          OPEN 940517.
 
85
UNIQUE IDENTIFIER         FDA/00629
PROTOCOL ID NUMBERS       FDA 234B
PROTOCOL TITLE            A Phase I Safety and Tolerability Study of
                          Four Doses of OPC-8212 (Vesnarinone) in
                          Advanced HIV Disease.
VERSION NUMBER & DATE     (940517)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and
                          tolerability of four doses of oral
                          vesnarinone in patients with advanced HIV
                          disease. Methodology: Fourteen patients per
                          dose level receive vesnarinone at 30, 60, 90,
                          and 120 mg/day for 12 weeks. At least seven
                          patients at a given dose level must have
                          completed 4 weeks of treatment before dose is
                          escalated in subsequent patients.
GENERAL DESCRIPTION       METHODOLOGY: Fourteen patients per dose level
                          receive vesnarinone at 30, 60, 90, and 120
                          mg/day for 12 weeks. At least seven patients
                          at a given dose level must have completed 4
                          weeks of treatment before dose is escalated
                          in subsequent patients.
PROTOCOL PHASE            Phase I B
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940401)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot. 2. CD4 count 50 -
                          300 cells/mm3 obtained 24 hours to 21 days
                          apart, with the second count obtained within
                          21 days prior to study entry. 3. No active
                          opportunistic infections. 4. No fever,
                          diarrhea, or Herpes zoster.
ELIGIBILITY               ASYM. AIDS.
OTHER PROTOCOL NUMBERS    22-93-252
STUDY DESIGN              Open Label; Dose Escalating; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 56 patients. (14 patients
                          at each of four dose levels)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 12 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count 50 - 300 cells/mm3. 3. No active
                          opportunistic infections. 4. No fever,
                          diarrhea, or Herpes zoster. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl. (men); >= 8.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 50 - 300 cells/mm3. (
                          100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1200
                          cells/mm3. Alkaline phosphatase < 5 x ULN.
                          TSH < 1.5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii,
                          candida, mycobacteria, and other
                          opportunistic infections. 2. Acyclovir for up
                          to 14 days for acute herpes outbreaks.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior history of cardiac disease. 2. History
                          of agranulocytosis or severe (grade 3 or
                          worse) drug-induced neutropenia or documented
                          abnormalities in granulocyte function. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active use of illicit drugs
                          (specifically cocaine, amyl nitrate, heroin,
                          and other cardioactive agents).
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 30 days
                          prior to study entry: 1. Erythropoietin,
                          transfusion, or blood product use. 2.
                          Radiation therapy (including electron beam
                          irradiation).
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. AZT, ddI, ddC,
                          d4T, or other nucleoside analog
                          antiretroviral therapy within 14 days prior
                          to study entry. 2. Prior cytotoxic
                          chemotherapy. 3. Acyclovir for herpes
                          prophylaxis within 48 hours prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral agents, including ddI, ddC,
                          AZT, and d4T. 2. Immunosuppressive agents. 3.
                          Investigational HIV drugs/therapies including
                          vaccines. 4. Interferon or other
                          immunomodulating agents. 5. Corticosteroids
                          (other than topical). 6. Hematopoietins. 7.
                          Megestrol acetate. 8. Agents known to cause
                          neutropenia. 9. Trimethoprim/sulfamethoxazole
                          in excess of 160 mg trimethoprim and 800 mg
                          sulfamethoxazole thrice weekly. 10. Cytotoxic
                          chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Clinically significant current cardiac
                          disease, including patients who exhibit long
                          QTC syndrome on EKG screening and who have an
                          abnormal cardiothoracic ratio on chest x-ray
                          at baseline. 2. Active malignancy (other than
                          cutaneous Kaposi's sarcoma or cutaneous basal
                          cell carcinoma or in situ carcinoma of the
                          cervix).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0210  Vesnarinone
TRADE NAME OF SUBSTANCE   Drug 1 OPC-8212
MANUFACTURERS             Drug 1: Otsuka America Pharmaceutical Inc
                          2440 Research Blvd Rockville, MD 20874
                          Contact: Dr Robert G Petit (301) 990-0030.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 30, 60, 90, or 120
                          mg/day for 12 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 30, 60, 90, or 120 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, tablets
SUPPORTING AGENCY         Otsuka America Pharmaceutical Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       81840-15-5 (OPC 8212)
LAST REVISION DATE        940401
ENTRY MONTH               9405
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon / Suite 130 Atlanta, GA 30308
                          Contact: Dr Melanie Thompson (404) 876-2317
                          OPEN 940401.
 
86
UNIQUE IDENTIFIER         FDA/00628
PROTOCOL ID NUMBERS       FDA 234A
PROTOCOL TITLE            A Phase I Study of Three Doses of OPC-8212
                          (Vesnarinone) in HIV-Infected Persons With
                          CD4+ Cell Number > 300 Cells/mm3.
VERSION NUMBER & DATE     (940622)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To examine the safety and tolerance
                          of three doses of oral vesnarinone in
                          HIV-infected patients with CD4 count > 300
                          cells/mm3. Methodology: Twelve patients per
                          dose level receive vesnarinone at 30, 60, and
                          90 mg/day for 12 weeks. At least six patients
                          at a given dose level must have completed 2
                          weeks of treatment before dose is escalated
                          in subsequent patients.
GENERAL DESCRIPTION       METHODOLOGY: Twelve patients per dose level
                          receive vesnarinone at 30, 60, and 90 mg/day
                          for 12 weeks. At least six patients at a
                          given dose level must have completed 2 weeks
                          of treatment before dose is escalated in
                          subsequent patients.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930801)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Asymptomatic HIV infections by
                          ELISA confirmed by a secondary test. 2. CD4
                          count > 300 cells/mm3 on two consecutive
                          occasions 48 hours to 21 days apart, with the
                          second count obtained within 14 days prior to
                          study entry. 3. No prior history of
                          AIDS-defining illness or current
                          constitutional symptoms of HIV disease.
ELIGIBILITY               ASYM.
OTHER PROTOCOL NUMBERS    22-93-251
STUDY DESIGN              Open Label; Dose Escalating; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 36 patients. (12 patients
                          at each of three dose levels)
PROTOCOL DETAILS          STUDY DURATION: 28 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic HIV infection. 2. CD4
                          count > 300 cells/mm3. 3. No prior
                          AIDS-defining illness or current
                          constitutional symptoms of HIV disease.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl. (men); >= 8.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 300 cells/mm3. ( 300 -
                          400 - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 90.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 2000
                          cells/mm3. Alkaline phosphatase < 5 x ULN.
                          TSH < 1.5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Chemoprophylaxis for Pneumocystis carinii,
                          candida, mycobacteria, and herpes simplex.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior history of cardiac disease. 2. History
                          of agranulocytosis or severe (grade 3)
                          drug-induced neutropenia or documented
                          abnormalities in granulocyte number or
                          function. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active illicit drug abuse.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation therapy
                          (including electron beam irradiation) within
                          30 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. AZT, ddI, and
                          ddC within 14 days prior to study entry. 2.
                          Prior cytotoxic chemotherapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral agents, including ddI, ddC,
                          and AZT. 2. Immunosuppressive agents. 3.
                          Investigational HIV drugs/therapies including
                          vaccines. 4. Interferon. 5. Steroids (other
                          than topical). 6. Hematopoietins. 7.
                          Megestrol acetate. 8.
                          Trimethoprim/sulfamethoxazole in excess of
                          160 mg trimethoprim and 800 mg
                          sulfamethoxazole thrice weekly. 9. Cytotoxic
                          chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Current history of cardiac disease, including
                          patients who exhibit long QT syndrome on EKG
                          screening. 2. Active malignancy other than
                          cutaneous basal cell carcinoma or in situ
                          carcinoma of the cervix.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0210  Vesnarinone
TRADE NAME OF SUBSTANCE   Drug 1 OPC-8212
MANUFACTURERS             Drug 1: Otsuka America Pharmaceutical Inc
                          2440 Research Blvd Rockville, MD 20874
                          Contact: Dr Robert G Petit (301) 990-0030.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 30, 60, or 90 mg/day
                          for 12 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 30, 60, or 90 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, tablets
SUPPORTING AGENCY         Otsuka America Pharmaceutical Inc.
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS
CAS REGISTRY NUMBER       81840-15-5 (OPC 8212)
LAST REVISION DATE        930801
ENTRY MONTH               9405
CALIFORNIA                UCLA School of Medicine / Division of
                          Hematology / Oncology Room 60 051 CHS Los
                          Angeles, CA 90012-1973 Contact: Dr Ronald
                          Mitsuyasu (310) 206-6414 OPEN 930801.
 
87
UNIQUE IDENTIFIER         FDA/00624
PROTOCOL ID NUMBERS       FDA 233A
PROTOCOL TITLE            A Phase I, Randomized, Single-Dose,
                          Placebo-Controlled Trial to Evaluate the
                          Safety and Pharmacokinetics of 524W91.
VERSION NUMBER & DATE     (940510)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To assess the safety and
                          pharmacokinetics of single oral doses of
                          524W91 administered in HIV-infected patients.
                          To determine the effects of food on
                          bioavailability of 524W91. Methodology:
                          Patients are randomized to receive six single
                          escalating doses of 524W91 or placebo, with
                          each dose separated by at least a 6-day
                          washout interval. Doses of 524W91 are 100,
                          200, 400, 400, 800, and 1200 mg. During the
                          two 400 mg doses, the effect of food on
                          pharmacokinetics will be investigated, with
                          one dose administered in conjunction with a
                          high-fat meal and one dose administered in a
                          fasted state.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive six single escalating doses of 524W91
                          or placebo, with each dose separated by at
                          least a 6-day washout interval. Doses of
                          524W91 are 100, 200, 400, 400, 800, and 1200
                          mg. During the two 400 mg doses, the effect
                          of food on pharmacokinetics will be
                          investigated, with one dose administered in
                          conjunction with a high-fat meal and one dose
                          administered in a fasted state.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940401)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by another test. 2. CD4 count >=
                          200 cells/mm3 within 14 days prior to study
                          entry. 3. No active opportunistic infection.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Single-Blind; Dose Escalating;
                          Pharmacokinetic; Randomized;
                          Placebo-Controlled
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 18 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Minimum of 11
                          weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count >= 200 cells/mm3. 3. No active
                          opportunistic infection. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 11.0 g/dl. (men); >= 10.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 200 cells/mm3. ( 200
                          - 300 - 400 - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1500 cells/mm3.
PATIENT AGE               AGE: 18 Years - 55 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 7 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   WEIGHT: 50 - 85 kg.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hepatitis, pancreatitis, or
                          cardiomyopathy within the past 5 years.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 56 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 7 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current alcohol or illicit
                          drug use that may affect patient compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1.
                          Antiretrovirals within 24 hours prior to each
                          dose. 2. Any prescription or over-the-counter
                          medications within 48 hours prior to each
                          dose. 3. Alcoholic beverages within 48 hours
                          prior to each dose.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded on the day of
                          each dose: 1. Antiretrovirals. 2. Any
                          prescription or over-the-counter medication.
                          3. Alcoholic beverages. 4. Coffee, tea, and
                          other xanthine-containing beverages and
                          foods.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy or other condition that would
                          confound study assessment or interfere with
                          ability to complete the study. 2.
                          Malabsorption syndrome or other
                          gastrointestinal dysfunction that might
                          interfere with gastrointestinal absorption.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0208  524W91
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Lisa Behrens (800) 722-9292 X 3633.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Single doses of 100,
                          200, 400, 400, 800, and 1200 mg (oplacebo),
                          with each dose separated by at least a 6-day
                          washout interval
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, capsules
SUPPORTING AGENCY         Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/*ADVERSE EFFECTS/
                          PHARMACOKINETICS
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
LAST REVISION DATE        940401
ENTRY MONTH               9405
CALIFORNIA                ViRx Medical Group 1375 Sutter Street Suite
                          407 San Francisco, CA 94102 Contact: Joyce
                          Amann (415) 474-4440 OPEN 940401.
 
88
UNIQUE IDENTIFIER         FDA/00683
PROTOCOL ID NUMBERS       FDA 232B
PROTOCOL TITLE            A Phase I/II Study of Safety, Tolerance,
                          Pharmacokinetics, and Anti-HIV Activity of
                          9-[2-(Bispivaloyloxymethyl)phosphonylmethoxye-
                          thyl]adenine (bis-POM PMEA) and Placebo in
                          HIV-Infected Patients.
VERSION NUMBER & DATE     (941028)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To study the safety, tolerance,
                          single and multiple dose pharmacokinetics,
                          and anti-HIV activity of bis-POM PMEA versus
                          placebo when administered orally on a daily
                          basis for 2 weeks to HIV-infected patients.
                          Methodology: Patients are randomized to
                          receive bis-POM PMEA at one of three fixed
                          dose levels or placebo daily for 2 weeks. At
                          each dose level, nine patients receive
                          bis-POM PMEA and three patients receive
                          placebo.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive bis-POM PMEA at one of three fixed
                          dose levels or placebo daily for 2 weeks. At
                          each dose level, nine patients receive
                          bis-POM PMEA and three patients receive
                          placebo.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941028)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA and
                          Western blot OR diagnosis of AIDS by CDC
                          criteria. 2. CD4 count >= 100 cells/mm3
                          within 35 days prior to study entry. 3. p24
                          antigen (immune-complex dissociated) >= 50
                          pg/ml.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    GS-93-402
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Drug Tolerance; Dose Escalating
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Pharmacokinetics, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 36 patients. (12 patients
                          at each of three dose levels)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. CD4 count >=
                          100 cells/mm3. 3. p24 antigen (immune-complex
                          dissociated) >= 50 pg/ml. 4. Life expectancy
                          of at least 6 months. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl. (women); >= 10.0
                          g/dl (men).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3. ( 100
                          - 200 - 300 - 400 - 500 - 600 - 700 - 800 -
                          plus ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.8 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 100 IU/l.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 100 IU/l.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.6 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Proteinuria < 2+. Lipase <= 260 IU/l.
                          Neutrophils >= 1000 cells/mm3. Prothrombin
                          time < 14 sec.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior prophylaxis
                          with aerosolized pentamidine, fluconazole,
                          ketoconazole, trimethoprim/sulfamethoxazole,
                          or dapsone.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Prophylaxis
                          with aerosolized pentamidine, fluconazole,
                          ketoconazole, trimethoprim/sulfamethoxazole,
                          or dapsone, provided a stable regimen has
                          been maintained for at least 4 weeks prior to
                          study entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of lactose intolerance. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse
                          (including alcohol) as determined by
                          questionnaire or positive drug screen.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 weeks
                          prior to study entry: 1. Any parenteral
                          antibiotic therapy. 2. Diuretics. 3.
                          Amphotericin B. 4. Didanosine (ddI). 5.
                          Fluconazole. 6. Foscarnet. 7. Ganciclovir. 8.
                          Interferon-alpha. 9. Interferon-beta. 10.
                          Isoniazid. 11. Aminoglycoside antibiotics.
                          12. Ketoconazole (topical allowed). 13.
                          Itraconazole. 14. Rifabutin. 15. Rifampin.
                          16. Stavudine (d4T). 17. Zalcitabine (ddC).
                          18. Zidovudine (AZT). 19. Lamivudine (3TC).
                          20. Any investigational agents (except with
                          sponsor approval). Excluded within 4 weeks
                          prior to study entry: Systemic therapy for
                          Kaposi's sarcoma.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          parenteral antibiotic therapy. 2. Diuretics.
                          3. Amphotericin B. 4. Didanosine (ddI). 5.
                          Fluconazole. 6. Foscarnet. 7. Ganciclovir. 8.
                          Interferon-alpha. 9. Interferon-beta. 10.
                          Isoniazid. 11. Aminoglycoside antibiotics.
                          12. Ketoconazole (topical allowed). 13.
                          Itraconazole. 14. Rifabutin. 15. Rifampin.
                          16. Stavudine (d4T). 17. Zalcitabine (ddC).
                          18. Zidovudine (AZT). 19. Lamivudine (3TC).
                          20. Any investigational agents (except with
                          sponsor approval). 21. Systemic therapy for
                          Kaposi's sarcoma.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active, serious infection (other than HIV
                          infection) requiring parenteral antibiotic
                          therapy. 2. Malignancy other than cutaneous
                          Kaposi's sarcoma. 3. Clinically significant
                          cardiac disease, including symptoms of
                          ischemia, congestive heart failure, or
                          arrhythmia. 4. Gastrointestinal malabsorption
                          syndrome. 5. Inability to take oral
                          medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0209  bis-POM PMEA
MANUFACTURERS             Drug 1: Gilead Sciences Inc 353 Lakeside
                          Drive Foster City, CA 94404 Contact: Dr Jay
                          Toole (415) 573-4751.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 125, 250, or 500 mg
                          (or placebo) daily for 2 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 125, 250, or 500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 2 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Requirement for
                          parenteral therapy of a serious illness.
SUPPORTING AGENCY         Gilead Sciences Inc.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adenine/ANALOGS & DERIVATIVES/*ADMINISTRATION
                          & DOSAGE/ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       106941-25-7
                          (9-(2-phosphonylmethoxyethyl)adenine)
LAST REVISION DATE        941028
ENTRY MONTH               9411
MARYLAND                  Johns Hopkins University 600 North Wolfe
                          Street Baltimore, MD 21205 Contact: Dr Paul
                          Lietman (410) 955-9707 OPEN 941028.
 
89
UNIQUE IDENTIFIER         FDA/00625
PROTOCOL ID NUMBERS       FDA 232A
PROTOCOL TITLE            Phase I Study of the Safety, Tolerance, and
                          Pharmacokinetics of
                          9-[2-(Bispivaloyloxymethyl)phosphonylmethoxye-
                          thyl]adenine (bis-POM PMEA) in HIV-Infected
                          Patients.
VERSION NUMBER & DATE     (940506)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To study the safety, tolerance, and
                          pharmacokinetics of a single dose of bis-POM
                          PMEA when administered by the oral route in
                          patients with HIV infection. Methodology:
                          Five patients are entered at each of three
                          dose levels of bis-POM PMEA: 200, 350, and
                          500 mg administered orally in a single dose.
GENERAL DESCRIPTION       METHODOLOGY: Five patients are entered at
                          each of three dose levels of bis-POM PMEA:
                          200, 350, and 500 mg administered orally in a
                          single dose.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940506)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: HIV seropositive by ELISA and
                          Western blot OR a clinical syndrome
                          indicative of AIDS by CDC criteria.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    GS-93-401
STUDY DESIGN              Single Dose; Dose Escalating; Drug Tolerance;
                          Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 15 patients. (5 patients
                          at each of three dose levels)
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection or
                          diagnosis of AIDS. 2. Life expectancy of at
                          least 3 months. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl. (women); >= 10.0
                          g/dl (men).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 70 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: < 1+ proteinuria. Lipase within normal
                          limits. Neutrophils >= 1000 cells/mm3. PT <
                          14 seconds. PTT < 40 seconds.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Prior AZT, ddI,
                          or ddC. 2. Prophylactic aerosolized
                          pentamidine, fluconazole, ketoconazole,
                          trimethoprim/sulfamethoxazole, or dapsone.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. AZT, ddI,
                          or ddC (provided patient has been on a stable
                          regimen for at least 4 weeks prior to study
                          entry). 2. Prophylactic aerosolized
                          pentamidine, fluconazole, ketoconazole,
                          trimethoprim/sulfamethoxazole, or dapsone
                          (provided patient has been on a stable
                          regimen for at least 4 weeks prior to study
                          entry).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse
                          (including alcohol or drug abuse).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 weeks
                          prior to study entry: 1. Diuretics. 2.
                          Amphotericin B. 3. Aminoglycoside
                          antibiotics. 4. Parenteral antibiotics. 5.
                          Other nephrotoxic agents. 6. Other
                          investigational agents. Excluded within 3
                          days prior to study entry: 1. Non-steroidal
                          anti-inflammatory drugs 2. Aspirin.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Diuretics. 2. Amphotericin B. 3.
                          Aminoglycoside antibiotics. 4. Parenteral
                          antibiotics. 5. Other nephrotoxic agents. 6.
                          Other investigational agents. 7.
                          Non-steroidal anti-inflammatory drugs. 8.
                          Aspirin.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active, serious infections (other than HIV
                          infections) that require parenteral
                          antibiotic therapy. 2. Clinically significant
                          cardiac disease, including symptoms of
                          ischemia, congestive heart failure, or
                          arrhythmia. 3. Gastrointestinal malabsorption
                          syndrome or inability to receive oral
                          medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0209  bis-POM PMEA
TRADE NAME OF SUBSTANCE   Drug 1 GS-0840
MANUFACTURERS             Drug 1: Gilead Sciences Inc 353 Lakeside
                          Drive Foster City, CA 94404 Contact: Dr Jay
                          Toole (415) 573-4751.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200, 350, or 500 mg
                          as a single dose
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, granules
SUPPORTING AGENCY         Gilead Sciences Inc.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adenine/ANALOGS & DERIVATIVES/*ADMINISTRATION
                          & DOSAGE/ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       106941-25-7
                          (9-(2-phosphonylmethoxyethyl)adenine)
LAST REVISION DATE        940506
ENTRY MONTH               9405
MARYLAND                  Johns Hopkins University 600 North Wolfe
                          Street Baltimore, MD 21205 Contact: Dr Paul
                          Lietman (410) 955-9707 OPEN 940506.
 
90
UNIQUE IDENTIFIER         FDA/00622
PROTOCOL ID NUMBERS       FDA 230A
PROTOCOL TITLE            A Phase II, Parallel Group, Randomized,
                          Placebo-Controlled Study of the Safety and
                          Efficacy of Thalidomide in Reducing Weight
                          Loss in Adults With HIV Wasting Syndrome.
VERSION NUMBER & DATE     (940428)
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety, antiviral
                          and anti-TNF-alpha activity, and preliminary
                          efficacy of thalidomide in reducing weight
                          loss in patients with HIV wasting syndrome.
                          Methodology: Patients are randomized to
                          receive either thalidomide at 100 or 200
                          mg/day or placebo for 8 weeks. Patients who
                          respond may continue in double-blinded
                          treatment for an additional 4 weeks;
                          nonresponding patients may receive
                          thalidomide at 200 mg/day for up to 4 weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either thalidomide at 100 or 200
                          mg/day or placebo for 8 weeks. Patients who
                          respond may continue in double-blinded
                          treatment for an additional 4 weeks;
                          nonresponding patients may receive
                          thalidomide at 200 mg/day for up to 4 weeks.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940428)
DISEASE STUDIED           Wasting syndrome.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 seropositive by ELISA
                          and Western blot. 2. Wasting as defined by
                          profound involuntary weight loss (> 10
                          percent of pre-morbid body weight) plus
                          weakness with or without documented fever for
                          30 days, in the absence of a concurrent
                          illness or condition other than HIV infection
                          that could explain the findings. 3. Negative
                          blood PCR for acid-fast bacteria (AFB) or a
                          negative AFB blood culture within 48 days
                          prior to study entry. 4. No active
                          opportunistic infection requiring systemic
                          therapy within 6 weeks prior to study entry.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    W-001
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          3-Arm; Parallel-Group; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 75 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. Wasting
                          syndrome. 3. Negative blood PCR for acid-fast
                          bacteria (AFB) or a negative AFB blood
                          culture within 48 days prior to study entry.
                          4. No active opportunistic infection
                          requiring systemic therapy within 6 weeks
                          prior to study entry. 5. Life expectancy of
                          at least 6 weeks. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5.0 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          Sodium 130 - 150 mEq/liter.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. No future reproduction.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required ONLY IF patient is
                          on antiretroviral therapy: Stable regimen of
                          AZT or ddI for at least 1 month prior to
                          study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Primary
                          prophylaxis for opportunistic infections (if
                          AFB blood culture negative). 2. Chronic
                          suppressive therapy (maintenance) for
                          opportunistic infections OTHER THAN
                          Mycobacterium avium Complex (MAC).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Any neoplasms other than non-medicated (i.e.,
                          not receiving systemic or intralesional
                          chemotherapy) Kaposi's sarcoma within 1 month
                          prior to study entry. 2. Prior intolerance to
                          thalidomide. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. Future reproduction.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug abuse within 3
                          months prior to study entry.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiotherapy
                          within 6 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiotherapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. ddC within 1
                          month prior to study entry. 2. Acute systemic
                          therapy for opportunistic infections within 6
                          weeks prior to study entry. 3. Agents that
                          are anabolic, catabolic, or immunomodulatory
                          (including interferons, megestrol,
                          dronabinol, oxandrolone, growth hormone,
                          systemic corticosteroids, and pentoxifylline)
                          within 30 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Chronic
                          suppressive therapy (maintenance) or
                          secondary prophylaxis for Mycobacterium avium
                          Complex (MAC) (suppressive therapy for other
                          opportunistic infections is allowed).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Chronic diarrhea (five or more unformed
                          stools per day). 2. Peripheral neuropathy of
                          grade 2 or worse. 3. Requirement for tube
                          feeding or intravenous feeding. 4. Any
                          disorder associated with moderate to severe
                          edema (e.g., cirrhosis, nephrosis, congestive
                          heart failure). 5. Inability to ingest at
                          least a maintenance diet based on present
                          weight. 6. Any condition that precludes study
                          participation. 7. Not under the care of a
                          primary physician.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0184  Thalidomide
MANUFACTURERS             Drug 1: Celgene Corporation 7 Powder Horn
                          Drive Warren, NJ 07059 Contact: Steve Thomas
                          (908) 805-3914 Contact: Victor Wright (908)
                          271-4119.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 or 200 mg (or
                          placebo) daily for at least 8 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 100 or 200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 8 weeks.
SUPPORTING AGENCY         Celgene Corporation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cachexia/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Thalidomide/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       50-35-1 (Thalidomide)
LAST REVISION DATE        940428
ENTRY MONTH               9405
CALIFORNIA                San Francisco General Hospital / Division of
                          Endocrinology 1001 Portrero Avenue Building
                          100 Room 286 San Francisco, CA 94110 Contact:
                          Kathleen Mulligan PhD (415) 206-5882 OPEN
                          940913.
CALIFORNIA                Marin County Specialty Clinic 250 Bon Air
                          Road Greenbrae, CA 94904 Contact: Clair
                          Ginesi (415) 499-7377 OPEN 940913.
NEW YORK                  Rockefeller University 1230 York Avenue New
                          York, NY 10021 Contact: Unspecified (212)
                          327-8375 OPEN 940428.
PENNSYLVANIA              Thomas Jefferson University 1015 Walnut
                          Street Philadelphia, PA 19107 Contact:
                          Unspecified (215) 955-8575 OPEN 940428.
 
91
UNIQUE IDENTIFIER         FDA/00619
PROTOCOL ID NUMBERS       FDA 229B
PROTOCOL TITLE            A Randomized, Multicenter, Double-Blind,
                          Phase III, Parallel Study of Zidovudine (AZT)
                          Alone Versus AZT Plus Zalcitabine
                          (Dideoxycytidine; ddC) Versus AZT Plus Ro
                          31-8959 (Saquinavir; HIV Proteinase
                          Inhibitor) Versus AZT Plus ddC Plus Ro
                          31-8959 in Previously Untreated or Minimally
                          Pretreated HIV-Infected Patients With CD4
                          Lymphocyte Counts From 50
VERSION NUMBER & DATE     (940926)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To compare, in zidovudine
                          (AZT)-naive patients, the safety, tolerance,
                          and efficacy of Ro 31-8959 alone versus AZT
                          alone versus AZT in combination with Ro
                          31-8959, dideoxycytidine (ddC), or both. To
                          compare various disease markers among the
                          different regimens. Methodology: Patients are
                          randomized to receive a minimum of 80 weeks
                          of AZT alone, AZT plus ddC, AZT plus Ro
                          31-8959, or all three drugs.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive a minimum of 80 weeks of AZT alone,
                          AZT plus ddC, AZT plus Ro 31-8959, or all
                          three drugs.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940926)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 seropositive by ELISA
                          confirmed by an alternative method. 2. CD4
                          count 50 - 350 cells/mm3. 3. No prior
                          antiretroviral therapy. 4. No acute serious
                          opportunistic infections requiring immediate
                          treatment. 5. No unexplained fever persisting
                          for 14 days within 90 days prior to study
                          entry. 6. No significant unexplained diarrhea
                          persisting for 14 days within 30 days prior
                          to study entry. 7. No visceral Kaposi's
                          sarcoma or lymphoma currently requiring
                          chemotherapy and/or radiotherapy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    SV 14604A. SV 14604C
STUDY DESIGN              Randomized; Double-Blind; Dose Comparison;
                          Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Comparative drug therapy,
                          Combination and single drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 3000 patients. (1000
                          patients from U.S.)
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count 50 - 350
                          cells/mm3. 3. No prior antiretroviral
                          therapy. 4. No acute serious opportunistic
                          infections requiring immediate treatment. 5.
                          No unexplained fever persisting for 14 days
                          within 90 days prior to study entry. 6. No
                          significant unexplained diarrhea persisting
                          for 14 days within 30 days prior to study
                          entry. 7. No visceral Kaposi's sarcoma or
                          lymphoma currently requiring chemotherapy
                          and/or radiotherapy. 8. Life expectancy of at
                          least 80 weeks. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 50 - 350 cells/mm3. (
                          100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils >= 1000 cells/mm3.
                          Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Local skin
                          radiotherapy.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Erythropoietin and G-CSF.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of non-Hodgkin's lymphoma. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiotherapy
                          (other than local skin radiotherapy).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Acute therapy
                          for opportunistic infection within 14 days
                          prior to study entry. 2. Prior HIV proteinase
                          inhibitor.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          investigational agents. 2. Antineoplastic
                          agents. 3. Biologic response modifiers
                          (including interferons). 4. Foscarnet. 5.
                          Anti-HIV drugs other than the study drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malabsorption. 2. Severe chronic diarrhea. 3.
                          Inadequate oral intake (unable to eat one or
                          more meals daily because of chronic nausea,
                          emesis, or abdominal/oral-esophageal
                          discomfort). 4. Any grade 3 or worse
                          toxicity. 5. Inability to comply with study
                          requirements.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Not geographically accessible
                          throughout study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0164  Ro 31-8959
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0015  Dideoxycytidine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 600 mg (or placebo)
                          TID for at least 80 weeks. Drug 2: 200 mg (or
                          placebo) TID for at least 80 weeks. Drug 3:
                          0.75 mg (or placebo) TID for at least 80
                          weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1800 mg. Drug 2: 600
                          mg. Drug 3: 2.25 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 200 mg capsules.
                          Drug 2: Oral, 100 mg capsules. Drug 3: Oral,
                          0.375 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 80 weeks.
OTHER TREATMENT INFO.     END POINT: Time to first AIDS-defining
                          clinical event or death, adverse effects.
SUPPORTING AGENCY         Hoffmann-La Roche, Incorporated.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              HIV Protease Inhibitors/ADMINISTRATION &
                          DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Isoquinolines/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (HIV Protease Inhibitors)
CAS REGISTRY NUMBER       127779-20-8 (Ro 31-8959)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940926
ENTRY MONTH               9409
NEW JERSEY                Hoffmann-La Roche, Incorporated 340 Kingsland
                          Street Nutley, NJ 07110-1199 Contact:
                          Professional Services (800) 526-6367 OPEN /
                          USA accrual 940926 ACTU: 0007.
 
92
UNIQUE IDENTIFIER         FDA/00618
PROTOCOL ID NUMBERS       FDA 229A
PROTOCOL TITLE            A Randomized, Double-Blind, Multicenter,
                          Parallel Study of Ro 31-8959 (Saquinavir; HIV
                          Proteinase Inhibitor) Alone, HIVID
                          (Dideoxycytidine; Zalcitabine, ddC) Alone,
                          and Both in Combination, as Treatment for
                          Advanced HIV Infection (CD4 50-300 Cells/mm3)
                          in Patients Discontinuing or Unable to Take
                          Retrovir (Zidovudine; AZT) Therapy.
VERSION NUMBER & DATE     (940926)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To compare the safety,
                          tolerance, and efficacy of Ro 31-8959 alone,
                          dideoxycytidine (ddC) alone, and both in
                          combination, in patients discontinuing or
                          unable to take zidovudine (AZT). SECONDARY:
                          To compare survival, changes in clinical
                          status and laboratory markers, decreases in
                          viral susceptibility, and quality of life
                          among the treatment groups. Methodology:
                          Patients are randomized to one of three
                          treatment regimens: ddC alone, Ro 31-8959
                          alone, and ddC plus Ro 31-8959. Treatment
                          continues for at least 48 weeks. Patients are
                          stratified by baseline CD4 count. (Per
                          09/26/94 amendment, a fourth arm, lower dose
                          Ro 31-8959 (200 mg q 8 hr) plus ddC, was
                          discontinued.)
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to one
                          of three treatment regimens: ddC alone, Ro
                          31-8959 alone, and ddC plus Ro 31-8959.
                          Treatment continues for at least 48 weeks.
                          Patients are stratified by baseline CD4
                          count. (Per 09/26/94 amendment, a fourth arm,
                          lower dose Ro 31-8959 (200 mg q 8 hr) plus
                          ddC, was discontinued.)
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Pending first patient enrolled (940404)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by ELISA
                          confirmed by Western blot or p24 antigen. 2.
                          CD4 count 50 - 300 cells/mm3. 3. Received
                          prior AZT that has been discontinued at least
                          28 days prior to study entry. 4. No active
                          opportunistic infection requiring immediate
                          treatment.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    NV 14256A. NV 14256B
STUDY DESIGN              Randomized; Double-Blind; Drug Tolerance;
                          3-Arm; Comparative; Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy, Combination and single drug
                          therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 900 patients. (300
                          patients on each of 3 treatment arms)
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 47 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count 50 - 300 cells/mm3. 3. Received prior
                          AZT that has been discontinued at least 28
                          days prior to study entry. 4. No active
                          opportunistic infection requiring immediate
                          treatment. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl. (May not be
                          transfusion dependent).
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 50 - 300 cells/mm3. (
                          100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 5.0 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          Serum amylase <= 1.5 x ULN (unless elevated
                          fraction is salivary amylase or patient has
                          macroamylasemia or in the setting of a normal
                          lipase value).
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Limited
                          localized radiation therapy to the skin.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Prior AZT.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. G-CSF and
                          erythropoietin. 2. Prophylaxis or chronic
                          suppression/maintenance therapy with dapsone,
                          aerosolized pentamidine, isoniazid, rifampin,
                          fluoroquinolones, pyrazinamide, ethambutol,
                          fluconazole, intraconazole, acyclovir,
                          clotrimazole, nystatin,
                          trimethoprim/sulfamethoxazole, pyrimethamine,
                          folic acid, sulfadiazine, clindamycin, and
                          fansidar.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of non-Hodgkin's lymphoma. 2.
                          Unexplained fever >= 38.5 C (101.5 F)
                          persisting for 14 days or longer within the
                          28 days prior to study entry. 3. Unexplained,
                          chronic diarrhea (defined as 3 or more loose
                          stools daily) persisting for 14 days or
                          longer within the 28 days prior to study
                          entry. 4. History of grade 2 or worse
                          peripheral neuropathy. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: More than 3 units
                          of blood in any 21-day period within 3 months
                          prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy other than limited localized therapy
                          to skin.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior HIV
                          proteinase inhibitor. 2. Prior antiretroviral
                          therapy other than AZT. 3. Acute therapy for
                          opportunistic infection within 14 days prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          antiretroviral drugs. 2. Experimental drugs.
                          3. Nephrotoxic or hepatotoxic drugs. 4. Drugs
                          likely to cause peripheral neuropathy. 5.
                          Antineoplastic agents. 6. Biologic response
                          modifiers.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Signs
                          or symptoms of peripheral neuropathy. 2.
                          Malabsorption or inadequate oral intake
                          (defined as unable to eat one or more meals
                          daily because of chronic nausea, emesis, or
                          abdominal/oral-esophageal discomfort. 3.
                          Malignancy, visceral Kaposi's sarcoma, or
                          lymphoma requiring systemic chemotherapy
                          and/or radiotherapy within the next 48 weeks.
                          4. Any grade 3 or worse laboratory or
                          clinical abnormality. 5. Inability to comply
                          with protocol requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0164  Ro 31-8959
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0015  Dideoxycytidine
TRADE NAME OF SUBSTANCE   Drug 2 Hivid
MANUFACTURERS             Drug 1: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
MANUFACTURERS             Drug 2: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 600 mg (or placebo)
                          q 8 hr for at least 48 weeks. (Per 09/26/94
                          amendment, the 200 mg dose given q 8 hr was
                          discontinuDrug 2: 0.75 mg (or placebo) q 8 hr
                          for at least 48 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1800 mg. Drug 2: 2.25
                          mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 200 mg capsules.
                          Drug 2: Oral, 0.375 mg tablets
OTHER TREATMENT INFO.     TREATMENT DURATION: 48 weeks.
OTHER TREATMENT INFO.     END POINT: Time to first clinical
                          AIDS-defining event or death, time to death,
                          change in weight and Karnofsky score, changes
                          in surrogate markers, quality of life,
                          adverse effects.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Requirement for
                          foscarnet or ganciclovir as treatment for
                          cytomegalovirus infections.
SUPPORTING AGENCY         Hoffmann-La Roche, Incorporated.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Isoquinolines/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zalcitabine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       127779-20-8 (Ro 31-8959)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        940404
ENTRY MONTH               9404
CALIFORNIA                UCLA School of Medicine / Division of
                          Hematology / Oncology Room 60 051 CHS Los
                          Angeles, CA 90012-1973 Contact: Dr Ronald
                          Mitsuyasu (310) 206-6414 OPEN 940412.
CALIFORNIA                UCLA / Care Center Room BH412 CHS / 10833 Le
                          Conte Avenue Los Angeles, CA 90024 Contact:
                          Dr David Hardy (310) 206-6414 OPEN 940412.
CALIFORNIA                UCLA / Harbor Medical Center 1000 West Carson
                          Street Torrance, CA 90505 Contact: Dr Gildon
                          Beall (310) 222-2365 OPEN 940412.
CALIFORNIA                Kaiser Foundation Hospital 25825 S. Vermont
                          Avenue Harbor City, CA 90710 Contact: Dr
                          Jared Spotkov (310) 325-5111 OPEN 940412.
CALIFORNIA                Pacific Oaks Medical Group / Research and
                          Scientific Invest 4940 Van Nuys Boulevard
                          Sherman Oaks, CA 91403 Contact: Dr Paul S
                          Berry (818) 990-3396 OPEN 940412.
CALIFORNIA                UCSD / Departments of Pathology and Medicine
                          0679 9500 Gilman Drive La Jolla, CA
                          92093-0679 Contact: Dr Douglas Richman (619)
                          552-7439 OPEN 940412.
CALIFORNIA                Sunnyvale Medical Center 596 Carroll Street
                          Sunnyvale, CA 94086 Contact: Dr Robert
                          Frascino (408) 524-5075 OPEN 940412.
CALIFORNIA                San Francisco General Hospital 995 Potrero
                          Avenue San Francisco, CA 94110 Contact: Dr
                          Paul Volberding (415) 476-4082 OPEN 940412.
CALIFORNIA                Davies Medical Center / Institute - HIV
                          Research & Treatment Castro and Duboce
                          Streets San Francisco, CA 94114 Contact: Dr
                          Stephen Follansbee (415) 565-6153 Contact:
                          (415) 565-6524 OPEN 940412.
CALIFORNIA                Mt Zion Medical Center / University
                          California San Francisco 1600 Divisadero
                          Street San Francisco, CA 94115 Contact: Dr
                          Jacob Lalezari (415) 476-6356 OPEN 940412.
CALIFORNIA                San Francisco Veterans' Administration
                          Medical Center 4150 Clement Street #111W San
                          Francisco, CA 94121 Contact: Manon Marovich
                          (415) 221-4810 X 394Contact: Sandra Charles
                          (415) 221-4810 X 394OPEN 940412 ACTU: 0807.
CALIFORNIA                University of California Davis / Department
                          of Internal Med 4301 X Street Sacramento, CA
                          95817 Contact: Dr Stuart H Cohen (916)
                          453-3741 OPEN 940412.
CALIFORNIA                Sunnybrook Medical Center 2075 Bayview Avenue
                          North / Room A226 Toronto Ontario, CA M4N 3M5
                          Contact: Dr Anita Rachlis 416-480-4689 OPEN
                          940620.
CALIFORNIA                Montreal General Hospital 1650 Cedar Avenue
                          Room B7117 Montreal Quebec, CA H3G1A4
                          Contact: Christos Tsoukas (514)272-0707 OPEN
                          940620.
CALIFORNIA                McMaster University Medical Center 1200 Main
                          Street West 2N29 Hamilton Ontario, CA L8N3Z5
                          Contact: Fiona M Smaill (905)521-2100 OPEN
                          940620.
CALIFORNIA                Clinique Medicale L Actuel 1001 boul de
                          Maissonneuve Est Suite 1130 Montreal Quebec,
                          CA H2L 4P9 Contact: Gervais Frechette
                          (514)524-1001 OPEN 940620.
CALIFORNIA                Southern Alberta HIV Clinic 1403 29th Street
                          NW Calgary Alberta, CA T2N 2T9 Contact: M
                          John Gill (403)670-2481 OPEN 940620.
DISTRICT OF COLUMBIA      Veterans Administration Medical Center 50
                          Irving Street N W Washington, DC 20422
                          Contact: Dr Fred Gordon (202) 745-8695
                          Contact: Patricia Ackerson (202) 745-8695
                          OPEN 940412.
FLORIDA                   Univ of Miami School of Med / Comprehensive
                          AIDS Program Div of Gen Med R-60A / 1800 NW
                          10th Avenue Miami, FL 33101 Contact: Margaret
                          A Fischl (305) 547-3847 OPEN 940412.
FLORIDA                   Miami Veterans Administration Medical Center
                          1201 NW 16th Street / Special Immunology Unit
                          (111-I) Miami, FL 33125 Contact: Dr Nancy
                          Klimas (305) 324-4455 X 433Contact: Dr Gordon
                          M Dickinson (305) 324-4455 OPEN 940412.
FLORIDA                   Stratogen Hospital 300 Arthur Godfrey Road /
                          2nd Floor Miami Beach, FL 33140 Contact: Dr
                          Lionel Resnick (305) 538-1400 OPEN 940503.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon / Suite 130 Atlanta, GA 30308
                          Contact: Dr Melanie Thompson (404) 876-2317
                          OPEN 940412.
GEORGIA                   West Paces Clinic Research 3193 Howell Mill
                          Road / Suite 306 Atlanta, GA 30327 Contact:
                          Dr Steven Marlowe (404) 350-5690 OPEN 940412.
ILLINOIS                  Rush Presbyterian - St Luke's Med Ctr /
                          Infectious Diseases 1753 West Congress
                          Parkway Chicago, IL 60612 Contact: Dr John
                          Pottage (312) 942-5862 OPEN 940412.
KANSAS                    University of Kansas 1010 North Kansas
                          Wichita, KS 67214 Contact: Dr Suzanne Gagnon
                          (316) 261-2855 OPEN 940412.
LOUISIANA                 Tulane University Medical Center / Infectious
                          Disease Sectio 1430 Tulane Avenue New
                          Orleans, LA 70112 Contact: Dr Newton E Hyslop
                          (504) 587-7316 OPEN 940412.
MASSACHUSETTS             New England Medical Center Hospitals / Div of
                          Geographic Med 750 Washington Street / NEMCH
                          67 Boston, MA 02111 Contact: Dr Paul Skolnik
                          (617) 350-8186 OPEN 940412.
MASSACHUSETTS             Massachusetts General Hospital / Dept Med
                          Harvard Med School Fruit Street Boston, MA
                          02114 Contact: Dr Martin S Hirach (617)
                          726-3815 OPEN 940412.
MASSACHUSETTS             New England Deaconess Medical Hospital /
                          Infectious Disease AK6 / One Autumn Street
                          Boston, MA 02215 Contact: Dr Davis Allan
                          (617) 632-0769 OPEN 940412.
MICHIGAN                  Harper Hospital Harper Professional Bldg /
                          Suite 202 / 4160 John R Detroit, MI 48201
                          Contact: Dr Crane (313) 745-9131 OPEN 940412.
MISSOURI                  Washington University School of Medicine
                          Campus Box 8011 / 4511 Forest Park Parkway /
                          Suite 304 St Louis, MO 63108 Contact: Dr
                          William Powderly (314) 361-5231 Contact: Mark
                          Myers (314) 454-0058 OPEN 940412.
NEW JERSEY                University of Medicine and Dentistry of NJ /
                          Dep of Medicine 185 South Orange Avenue
                          Newark, NJ 08103 Contact: Dr Dennis Cunniff
                          (201) 982-7598 OPEN 940412.
NEW JERSEY                University of Medicine and Denistry NJ /
                          Cooper Hospital Education and Research
                          Building / 401 Haddon Ave / Rm 270 Camden, NJ
                          08103 Contact: Lynn Jeffries (609) 757-9783
                          OPEN 940412.
NEW YORK                  Beth Israel Medical Center / Division of
                          Infectious Diseases 10th Flr Pavilion / 1st
                          Avenue at 16th Street New York, NY 10003
                          Contact: Wendy Lupin (212) 420-4432 Contact:
                          Peter Berge (212) 420-4519 OPEN 940412.
NEW YORK                  St. Vincent's Hospital Medical Center 412
                          Sixth Avenue 4th Floor New York, NY 10011
                          Contact: Dr Ramon Torres (212) 604-7000
                          Contact: Karen MacIntyre (212) 604-8319 OPEN
                          940412.
NEW YORK                  Harkness Pavilion 5th Floor Room 516 / 180
                          Fort Washington Avenue New York, NY 10032
                          Contact: Dr Jay Dobkin (212) 305-8507 OPEN
                          940412.
NEW YORK                  Albany Medical College / Division of Medical
                          Oncology A-52 47 New Scotland Avenue Albany,
                          NY 12208 Contact: Dr Scot Remick (518)
                          262-6713 OPEN 940412.
OHIO                      Ohio State University Hospital Doan Hall /
                          Room N 1148 / 410 West Tenth Avenue Columbus,
                          OH 43210 Contact: Dr Maybeth Ramundo (614)
                          293-8112 OPEN 940412.
OREGON                    Oregon Health Sciences University 3181
                          Southwest Sam Jackson Road Portland, OR 97201
                          Contact: Mark Loveless (503) 295-0950 OPEN
                          940412.
OTHER                     San Juan Veterans Administration Medical
                          Center One Veterans Plaza 111 San Juan, PR
                          00927-5800 Contact: Dr Carlos Ramirez-Ronda
                          (809) 758-6900 OPEN 940412.
PENNSYLVANIA              Thomas Jefferson Medical College 1015 Walnut
                          Street - 701 Curtis Building Philadelphia, PA
                          19107 Contact: Dr Stephen Hauptman (215)
                          955-7785 Contact: Roberta Benjamin OPEN
                          940412.
PENNSYLVANIA              Tuttleman Cancer Center / Graduate Hospital
                          of Philadelphia 1840 South Street
                          Philadelphia, PA 19146 Contact: Dr David
                          Henry (215) 893-7520 OPEN 940412.
 
93
UNIQUE IDENTIFIER         FDA/00614
PROTOCOL ID NUMBERS       FDA 228B
PROTOCOL TITLE            A Double-Blind, Randomized, Dose-Response
                          Study of Three Fixed Doses of Delavirdine
                          Mesylate (U-90152S) in Combination With
                          Zidovudine (AZT) Versus AZT Alone in HIV-1
                          Infected Individuals With CD4 Counts of
                          200-500/mm3.
VERSION NUMBER & DATE     (940331)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety, tolerance,
                          efficacy, and pharmacokinetics of three fixed
                          doses of delavirdine mesylate (U-90152S) in
                          combination with zidovudine (AZT) versus AZT
                          alone in HIV-positive patients. Methodology:
                          Patients are randomized to receive U-90152S
                          plus AZT or AZT alone. Didanosine may be
                          added if the CD4 count falls below 50 percent
                          of baseline at two consecutive visits 72 or
                          more hours apart or if the patients develops
                          a new or recurrent AIDS-defining illness.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive U-90152S plus AZT or AZT alone.
                          Didanosine may be added if the CD4 count
                          falls below 50 percent of baseline at two
                          consecutive visits 72 or more hours apart or
                          if the patients develops a new or recurrent
                          AIDS-defining illness.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940315)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 seropositive by EIA or
                          ELISA and Western blot or HIV culture. 2. CD4
                          count 200 - 500 cells/mm3 within 35 days
                          prior to study entry. 3. No active or acute
                          (onset within the past month) opportunistic
                          infections such as active cryptococcosis,
                          pneumocystis carinii, herpes zoster,
                          histoplasmosis, or cytomegalovirus (CMV).
                          NOTE: Patients with cutaneous Kaposi's
                          sarcoma requiring no systemic therapy are
                          permitted.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    M/3331/0021
STUDY DESIGN              Randomized; Multicenter; Double-Blind;
                          Parallel-Group; Drug Combination;
                          Comparative; Drug Tolerance; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination and single drug
                          therapy, Combination and single
                          pharmacokinetics.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 86 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 seropositivity. 2. CD4 count
                          200 - 500 cells/mm3. 3. No active or acute
                          (onset within the past month) opportunistic
                          infections such as active cryptococcosis,
                          pneumocystis carinii, herpes zoster,
                          histoplasmosis, or cytomegalovirus (CMV). 4.
                          Consent of parent or guardian if less than 18
                          years of age. 5. Understanding of potential
                          risk to fetus related to study participation.
                          6. Acceptable medical history, physical exam,
                          EKG, and chest x-ray during screening. NOTE:
                          Patients with cutaneous Kaposi's sarcoma
                          requiring no systemic therapy are permitted.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT AGE               AGE: 14 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 15 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior AZT (no more
                          than 6 months total).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of pancreatitis within the past 2
                          years. 2. History of clinically significant
                          nervous system or muscle disease, seizure
                          disorder, AIDS dementia, or psychiatric
                          disorder that would preclude study
                          compliance. 3. History of grade 2 or worse
                          peripheral neuropathy. 4. Intolerance to AZT
                          in previous treated patients. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 13 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 15 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than 6
                          months total of prior AZT. 2. Any prior ddC,
                          d4T, 3TC, or ddI. 3. Prior nonnucleoside
                          reverse transcriptase inhibitors, including
                          L-drugs, nevirapine, TIBO, HEPT, delavirdine,
                          atevirdine, and alpha-APA. 4. Other
                          investigational antiretroviral medications
                          (including foscarnet) or immunomodulators
                          (including all interferons) within 21 days
                          prior to initial study drug dose. 5. Prior
                          prophylactic or therapeutic HIV-1 gp120 or
                          160 vaccines. 6. Rifampin, rifabutn,
                          astemizole, loratadine, or terfenadine within
                          21 days prior to initial study drug dose. 7.
                          Any unapproved investigational medication for
                          any indication within 21 days prior to
                          initial study drug dose. 8. Any
                          enzyme-inducing drugs known to affect
                          cytochrome P450 3A, (e.g., ketoconazole,
                          fluconazole, isoniazid, itraconazole, etc.)
                          within 21 days prior to initial study drug
                          dose.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active tuberculosis that is sensitive to
                          rifampin. 2. Inability to swallow numerous
                          tablets. 3. Clinically significant active or
                          acute medical problems, including progressive
                          multifocal leukoencephalopathy, lymphoma, or
                          malignancy requiring systemic therapy. 4.
                          Clinically significant hypersensitivity to
                          piperazine-type drugs (e.g., Antepar and
                          Stelazine). 5. Grade 2 or worse baseline
                          organ function. NOTE: Hemophiliacs with grade
                          2 bilirubin, alkaline phosphatase, SGOT, or
                          SGPT will be considered if these values have
                          been stable over the past year. NOTE:
                          Patients with suspected Gilbert's syndrome
                          will be considered if bilirubin is grade 2 or
                          better.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0166  U-90152
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
MANUFACTURERS             Drug 1: The Upjohn Company 7000 Portage Road
                          Kalamazoo, MI 49001 Contact: James VanSweden
                          (616) 323-4696.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, compressed
                          film-coated tablets
SUPPORTING AGENCY         The Upjohn Company.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADVERSE EFFECTS/
                          PHARMACOKINETICS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940315
ENTRY MONTH               9404
ALABAMA                   University of Alabama at Birmingham 933 19th
                          Street S/1917 Research Clinic Room 219
                          Birmingham, AL 35294-2041 Contact: Robin
                          Noles (205) 934-7349 OPEN 940315.
CALIFORNIA                CARE / UCLA Medical Center / Department of
                          Medicine 10833 Le Conte Avenue / Room BH 413
                          / CHS Los Angeles, CA 90024 Contact: Lori
                          Bort (310) 206-6414 OPEN 940315.
CALIFORNIA                University of Southern California / LAC - USC
                          Medical Cntr 1175 North Cummings Street /
                          5021 Clinic Los Angeles, CA 90033-1079
                          Contact: Novella Quesada (213) 343-8277 OPEN
                          940315.
CALIFORNIA                King / Drew Medical Center 12021 South
                          Wilmington Avenue Los Angeles, CA 90059
                          Contact: Bessie Hughes (310) 603-4213 OPEN
                          940315.
CALIFORNIA                Harbor / UCLA Medical Center PO Box 449 /
                          1000 W Carson St Torrance, CA 90509 Contact:
                          Jeannette Shelly (310) 222-3848 OPEN 940315.
CALIFORNIA                Shared Medical Research Foundation 5620
                          Wilbur / S 322 Tarzana, CA 91356 Contact: Eve
                          Zisman (818) 345-2172 OPEN 940315.
CALIFORNIA                UCSD / Center for Special Immunology 2918
                          Fifth Ave / Suite 300 San Diego, CA 92103
                          Contact: Dr Scott Loss (619) 543-8080 OPEN
                          940315.
CALIFORNIA                UCI Medical Center Building 53 Route 81 / 101
                          City Drive South Orange, CA 92668 Contact:
                          Josephine Mosquara (714) 456-7612 OPEN
                          940315.
CALIFORNIA                California Medical Research Group 8636 North
                          First Street / Suite 120 Fresno, CA 93726
                          Contact: Margaret Northrop (209) 221-1327
                          OPEN 940315.
CALIFORNIA                ACRC AIDS Community Research Consortium 1048
                          El Camino Real / Suite A Redwood City, CA
                          94063 Contact: Deborah Harriss (415) 364-6564
                          OPEN 940315.
CALIFORNIA                ViRx Medical Group 1375 Sutter Street Suite
                          407 San Francisco, CA 94102 Contact: Joyce
                          Amann (415) 474-4440 OPEN 940315.
CALIFORNIA                St Francis Hospital / Clinical Research 909
                          Hyde Street San Francisco, CA 94109 Contact:
                          Max Huckabee (415) 353-6299 OPEN 940315.
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 940315 ACTU: 0808.
CALIFORNIA                Davies Medical Center / Institute for HIV
                          Treatment and Rsch Castro and Duboce Streets
                          San Francisco, CA 94114 Contact: Sue Kelly
                          (415) 565-6153 OPEN 940315.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue /
                          Suite 235 Berkeley, CA 94705 Contact: Sherry
                          Lyman (510) 204-1870 Contact: Dr Carol
                          Brosgart (510) 204-1201 OPEN 940315.
CALIFORNIA                U of CA / Davis Med Ctr / AIDS and Related
                          Disorders Clinic 2221 Stockton Blvd / PCC Rm
                          3107 Sacramento, CA 95817 Contact: Sheila
                          Enders (916) 734-7004 OPEN 940315.
COLORADO                  University Hospital / Univ of Colorado Health
                          Sci Ctr Box B-163 / 4200 East Ninth Avenue
                          Denver, CO 80262 Contact: Graham Ray (303)
                          270-8551 OPEN 940315 ACTU: 0105.
DISTRICT OF COLUMBIA      Georgetown University / Medical Center 3800
                          Reservoir Road Washington, DC 20007 Contact:
                          Sara Swartzendruber (202) 687-1079 OPEN
                          940315.
DISTRICT OF COLUMBIA      George Washington University / Medical
                          Faculty Associates 2150 Pennsylvania Avenue /
                          Suite 5-419 Washington, DC 20037 Contact:
                          Barbara Lewis (202) 994-2417 OPEN 940315.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue 1st Floor Eliot Building
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 OPEN 940315.
FLORIDA                   Caremark Incorporated 3345 Burns Road / Suite
                          302 Palm Beach Gardens, FL 33410 Contact:
                          Unspecified (407) 775-7544 OPEN 940315.
FLORIDA                   St Josephs Hospital / Infectious Disease
                          Research Institute 4600 N Habana Ave / Suite
                          14 Tampa, FL 33614 Contact: Allis Emmett
                          (813) 870-4760 OPEN 940315.
GEORGIA                   Southeast Clinical Resources 1758 A Century
                          Boulevard Atlanta, GA 30345 Contact: Kym
                          Prieto (404) 325-4677 OPEN 940315.
IOWA                      University of Iowa 200 Hawkins Drive /
                          Southwest 54 GH Iowa City, IA 52242 Contact:
                          Unspecified (319) 356-3168 OPEN 940315.
ILLINOIS                  Rush Presbyterian / St Luke's Medical Center
                          Room 140 - 143 Academic Facility / 600 South
                          Paulina Chicago, IL 60612 Contact: Marilyn
                          Ashmann (312) 942-5865 OPEN 940315.
ILLINOIS                  University of Illinois 840 South Wood Street
                          Chicago, IL 60612 Contact: Unspecified (312)
                          996-6732 OPEN 940315.
INDIANA                   Indiana University Medical School /
                          Department of Medicine 550 N University Blvd
                          / Room 5550 Indianapolis, IN 46202 Contact:
                          Jean Craft (317) 274-8456 OPEN 940315.
KANSAS                    University of Kansas School of Med /
                          University Hospital 39th at Rainbow Kansas
                          City, KS 66160-7354 Contact: Jane Harms (913)
                          588-6035 Contact: (913) 588-3896 OPEN 940315.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 940315.
KENTUCKY                  University of Kentucky Medical Center 800
                          Rose Street / Room MN633A Lexington, KY 40536
                          Contact: Karen Bowen (606) 257-5473 OPEN
                          940315.
LOUISIANA                 Tulane University Medical School / AIDS
                          Clinical Trials Unit 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Russell
                          Strada (504) 584-3605 OPEN 940315.
MASSACHUSETTS             Baystate Medical Center / Infectious Disease
                          Division 759 Chestnut Street Springfield, MA
                          01199 Contact: Deborah Prescod (413) 784-3046
                          OPEN 940315.
MASSACHUSETTS             University of Massachusetts Medical School 55
                          Lake Avenue North / Div Infectious Diseases
                          Worcester, MA 01655 Contact: Joan L Avto
                          (508) 856-2456 Contact: (508) 856-2666 OPEN
                          940315 ACTU: 3001.
MASSACHUSETTS             Massachusetts General Hospital Gray 5 /
                          Infectious Disease Unit Boston, MA 02114
                          Contact: Ellen Godfrey (617) 726-5598
                          Contact: Teri Flynn (617) 726-3819 OPEN
                          940315.
MASSACHUSETTS             Brigham Women's Hospital / Infectious Disease
                          Division 75 Francis Street Boston, MA 02115
                          Contact: Ann Elperin (617) 732-5885 OPEN
                          940315.
MASSACHUSETTS             Boston City Hospital / FGH-1 818 Harrison
                          Avenue / Thorndike Room 209 Boston, MA 02118
                          Contact: Nancy Reinhalter (617) 534-5404 OPEN
                          940315.
MASSACHUSETTS             New England Deaconess Hospital 185 Pilgrim
                          Road Boston, MA 02215 Contact: Helen Fitch
                          (617) 735-0785 OPEN 940315 ACTU: 0103.
MAINE                     AIDS Consultation Service / Maine Medical
                          Center 22 Bramhall Street Portland, ME 04102
                          Contact: Sandy Putnam (207) 871-2995 OPEN
                          940315.
MARYLAND                  University of Maryland / SOM / Department of
                          Med / Adult HIV Box 165 / 22 S Green Street
                          Baltimore, MD 21201 Contact: Andrea Fisch
                          (410) 706-1806 OPEN 940315.
MARYLAND                  Johns Hopkins University Hospital Richard
                          Starr Ross Rsch Bldg / 720 Rutland Avenue
                          Room 1159 Baltimore, MD 21205-2196 Contact:
                          Becky Becker (410) 955-4370 OPEN 940315.
MICHIGAN                  University of Michigan / Division of
                          Infectious Diseases 3116 B Taubman Center Ann
                          Arbor, MI 48109 Contact: unspecified (313)
                          936-5205 OPEN 940315.
MICHIGAN                  Harper Hospital Harper Professional Bldg /
                          Suite 202 / 4160 John R Detroit, MI 48201
                          Contact: Dr Crane (313) 745-9131 OPEN 940315.
MICHIGAN                  Henry Ford Hospital / Infectious Diseases
                          2799 West Grand Blvd / CFP 111 Detroit, MI
                          48202 Contact: Ann Marie Krystoforsky (313)
                          876-2798 OPEN 940315.
MINNESOTA                 St Paul Ramsey Medical Center / HIV Program
                          Office 640 Jackson Street St Paul, MN 55101
                          Contact: Holly Melroe (612) 221-1280 OPEN
                          940315.
MISSOURI                  Washington University Clinical Trials Unit
                          4511 Forest Park Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0058 OPEN
                          940315.
MISSOURI                  University of Missouri Kansas City / School
                          of Medicine 2411 Holmes Kansas City, MO 64108
                          Contact: Donna Simpson (816) 556-3478 OPEN
                          940315.
NORTH CAROLINA            University of NC / School of Medicine / Div
                          Infec Diseases 547 Burnett Womack Building /
                          CB7030 Chapel Hill, NC 27599-7030 Contact:
                          Barbara Longmeyer (919) 966-7883 OPEN 940315.
NORTH CAROLINA            Duke University Medical Center / Infectious
                          Diseases Clinic PO Box 3284 Durham, NC 27710
                          Contact: Ken Ship (919) 684-5260 OPEN 940315.
NORTH CAROLINA            Carolinas Medical Center / Department of
                          Internal Medicine 1000 Blythe Blvd AHEC Room
                          507 Charlotte, NC 28203 Contact: Joan Connell
                          (704) 355-5292 Contact: (704) 355-3165 OPEN
                          940315 ACTU: 3204.
NEBRASKA                  University of Nebraska Medical Center / HIV
                          Clinic 600 South 42nd Street Omaha, NE
                          68198-5130 Contact: Colleen R Kelly (402)
                          559-8163 OPEN 940315.
NEW JERSEY                Jersey Shore Medical Center 1945 Route #33
                          Neptune, NJ 07754 Contact: Susan Bataille
                          (908) 776-4700 OPEN 940315.
NEW YORK                  CRIA of New York 275 Seventh Avenue / 20th
                          Floor New York, NY 10001 Contact: Bette Smith
                          (212) 924-3934 OPEN 940315.
NEW YORK                  Beth Israel Medical Center / Department of
                          Medicine First Avenue and 16th Street New
                          York, NY 10003 Contact: Alice Fox (212)
                          420-4519 OPEN 940315.
NEW YORK                  St Vincents Hospital and Medical Center 412
                          Sixth Ave / 4th Floor New York, NY 10011
                          Contact: Noel George (212) 604-7625 OPEN
                          940315.
NEW YORK                  St Luke / Roosevelt Hospital Center / Dir HIV
                          / AIDS CTP 428 West 59th Street New York, NY
                          10019 Contact: Julie Rivera (212) 523-6723
                          OPEN 940315.
NEW YORK                  New York Hospital / Cornell Medical Center
                          505 East 70th Street New York, NY 10021
                          Contact: Paul Douglas (212) 746-4177 OPEN
                          940315.
NEW YORK                  Mount Sinai Hospital / Clinical Trials Unit 1
                          Gustave Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-0433 OPEN
                          940315.
NEW YORK                  Westchester County Medical Center /
                          Department of Infec Dis 209 South East / Macy
                          Pavillion Valhalla, NY 10595 Contact: Gilda
                          Forseter (914) 285-1561 Contact: Diane
                          Holmgren (914) 285-7400 Contact: Dr Marissa
                          Montecalvo (914) 285-8865 Contact: Dr Gary
                          Wormser (914) 285-8865 OPEN 940315.
NEW YORK                  SUNY at Stony Brook Health Sciences Center /
                          Div Infect Dis HSC T 15 Room 080 Stony Brook,
                          NY 11794-8153 Contact: Ruth Ann Burk (516)
                          444-1658 OPEN 940315.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 940315 ACTU: 7401.
NEW YORK                  SUNY at Buffalo / Erie County Medical Center
                          462 Grider Street Buffalo, NY 14215 Contact:
                          David Meger (716) 898-4482 OPEN 940315.
NEW YORK                  Community Health Network 758 South Avenue
                          Rochester, NY 14620 Contact: Lorraine Newcomb
                          (716) 244-9000 OPEN 940315.
NEW YORK                  University of Rochester Medical Center 601
                          Elmwood Avenue / Box 689 Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940315.
OHIO                      University Hospitals of Cleveland/Case
                          Western Reserve Univ 206 Cornell Road
                          Cleveland, OH 44106 Contact: Michael Chance
                          (216) 844-8175 OPEN 940315.
OHIO                      University of Cincinnati Medical Center /
                          Holmes Division Eden and Bethesda Avenues
                          Cincinnati, OH 45267 Contact: Jill Leonard
                          (513) 558-8373 OPEN 940315.
OREGON                    Research and Education Group 2701 NW Vaughn
                          Streets / 770 Portland, OR 97210 Contact:
                          Sallie Israelit (503) 229-8428 OPEN 940315.
OTHER                     University of Puerto Rico / Department of
                          Medicine Medical Science Center / Room A 838
                          San Juan, PR 00936 Contact: Unspecified (809)
                          754-3755 OPEN 940315.
PENNSYLVANIA              University of Pittsburgh / School of Medicine
                          3515 Fifth Avenue Pittsburgh, PA 15261
                          Contact: Rosella Rosener (412) 647-8125 OPEN
                          940315.
PENNSYLVANIA              Pennsylvania State University / Hershey
                          Medical Center 500 Univ Drive / PO Box 850 /
                          Biomedical Rsrch Bldg C-6833 Hershey, PA
                          17033 Contact: Francine Damianos (717)
                          531-7488 OPEN 940315.
PENNSYLVANIA              University of Pennsylvania / Dept of Infect
                          Dis / HIV Clinic 536 Johnson Pavilion / 6073
                          Philadelphia, PA 19104 Contact: Heidi Lehman
                          (215) 662-6932 OPEN 940315.
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 940315.
PENNSYLVANIA              Oncology and Hematology Association 1840
                          South Street / 2nd Floor Philadelphia, PA
                          19146 Contact: Barbara Rensman (215) 893-7541
                          OPEN 940315.
RHODE ISLAND              Stratogen Health / Independent Research
                          Nurses 769 Park Ave Cranston, RI 02910
                          Contact: Lynn Haughey (401) 781-2400 OPEN
                          940315.
SOUTH CAROLINA            Medical University of South Carolina 171
                          Ashley Avenue Charleston, SC 29425 Contact:
                          Unspecified (803) 792-4541 OPEN 940315.
 
94
UNIQUE IDENTIFIER         FDA/00613
PROTOCOL ID NUMBERS       FDA 228A
PROTOCOL TITLE            A Double-Blind, Randomized, Comparative Study
                          of Delavirdine Mesylate (U-90152S) in
                          Combination With Didanosine (ddI) Versus ddI
                          Alone in HIV-1 Infected Individuals With CD4
                          Counts of <= 300/mm3.
VERSION NUMBER & DATE     (940331)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety, tolerance,
                          pharmacokinetics, and efficacy of delavirdine
                          mesylate (U-90152S) in combination with
                          didanosine (ddI) versus ddI alone in
                          HIV-positive patients
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940315)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV-1 seropositive by EIA or
                          ELISA and Western blot or HIV culture. 2. CD4
                          count <= 300 cells/mm3 within 35 days prior
                          to study entry. 3. No active or acute (onset
                          within the past month) opportunistic
                          infections such as active cryptococcosis,
                          pneumocystis carinii, herpes zoster,
                          histoplasmosis, or cytomegalovirus (CMV).
                          NOTE: Patients with cutaneous Kaposi's
                          sarcoma requiring no systemic therapy are
                          permitted.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    M/3331/0017
STUDY DESIGN              Randomized; Multicenter; Double-Blind;
                          Parallel-Group; Drug Combination; Drug
                          Tolerance; Comparative; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination and single drug
                          therapy, Combination and single
                          pharmacokinetics.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 84 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV-1 seropositivity. 2. CD4 count
                          <= 300 cells/mm3. 3. No active or acute
                          (onset within the past month) opportunistic
                          infections such as active cryptococcosis,
                          pneumocystis carinii, herpes zoster,
                          histoplasmosis, or cytomegalovirus (CMV). 4.
                          Consent of parent or guardian if less than 18
                          years of age. 5. Understanding of potential
                          risk to fetus related to study participation.
                          6. Acceptable medical history, physical exam,
                          EKG, and chest x-ray during screening. NOTE:
                          Patients with cutaneous Kaposi's sarcoma
                          requiring no systemic therapy are permitted.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 300 cells/mm3. ( 0 -
                          100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT AGE               AGE: 14 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 15 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT therapy at
                          some time prior to screening.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: AZT.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of pancreatitis within the past 2
                          years. 2. History of clinically significant
                          nervous system or muscle disease, seizure
                          disorder, AIDS dementia, or psychiatric
                          disorder that would preclude study
                          compliance. 3. History of grade 2 or worse
                          peripheral neuropathy. 4. Intolerance to ddI
                          in previous treated patients. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 13 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 15 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than 4
                          months total of prior ddI. 2. Any prior ddC,
                          d4T, or 3TC. 3. Prior nonnucleoside reverse
                          transcriptase inhibitors, including L-drugs,
                          nevirapine, TIBO, HEPT, delavirdine,
                          atevirdine, and alpha-APA. 4. Other
                          investigational antiretroviral medications
                          (including foscarnet) or immunomodulators
                          (including all interferons) within 21 days
                          prior to initial study drug dose. 5. Prior
                          prophylactic or therapeutic HIV-1 gp120 or
                          160 vaccines. 6. Rifampin, rifabutn,
                          astemizole, loratadine, or terfenadine within
                          21 days prior to initial study drug dose. 7.
                          Any unapproved investigational medication for
                          any indication within 21 days prior to
                          initial study drug dose.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active tuberculosis that is sensitive to
                          rifampin. 2. Inability to swallow numerous
                          tablets. 3. Clinically significant active or
                          acute medical problems, including progressive
                          multifocal leukoencephalopathy, lymphoma, or
                          malignancy requiring systemic therapy. 4.
                          Clinically significant hypersensitivity to
                          piperazine-type drugs (e.g., Antepar and
                          Stelazine). 5. Grade 2 or worse baseline
                          organ function. NOTE: Hemophiliacs with grade
                          2 bilirubin, alkaline phosphatase, SGOT, or
                          SGPT will be considered if these values have
                          been stable over the past year. NOTE:
                          Patients with suspected Gilbert's syndrome
                          will be considered if bilirubin is grade 2 or
                          better.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0166  U-90152
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
MANUFACTURERS             Drug 1: The Upjohn Company 7000 Portage Road
                          Kalamazoo, MI 49001 Contact: James VanSweden
                          (616) 323-4696.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, compressed
                          film-coated tablets
SUPPORTING AGENCY         The Upjohn Company.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADVERSE EFFECTS/
                          PHARMACOKINETICS/*THERAPEUTIC USE
MESH HEADING              Didanosine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        940315
ENTRY MONTH               9404
ALABAMA                   University of Alabama at Birmingham 933 19th
                          Street S/1917 Research Clinic Room 219
                          Birmingham, AL 35294-2041 Contact: Robin
                          Noles (205) 934-7349 OPEN 940315.
CALIFORNIA                CARE / UCLA Medical Center / Department of
                          Medicine 10833 Le Conte Avenue / Room BH 413
                          / CHS Los Angeles, CA 90024 Contact: Lori
                          Bort (310) 206-6414 OPEN 940315.
CALIFORNIA                University of Southern California / LAC - USC
                          Medical Cntr 1175 North Cummings Street /
                          5021 Clinic Los Angeles, CA 90033-1079
                          Contact: Novella Quesada (213) 343-8277 OPEN
                          940315.
CALIFORNIA                King / Drew Medical Center 12021 South
                          Wilmington Avenue Los Angeles, CA 90059
                          Contact: Bessie Hughes (310) 603-4213 OPEN
                          940315.
CALIFORNIA                Harbor / UCLA Medical Center PO Box 449 /
                          1000 W Carson St Torrance, CA 90509 Contact:
                          Jeannette Shelly (310) 222-3848 OPEN 940315.
CALIFORNIA                Shared Medical Research Foundation 5620
                          Wilbur / S 322 Tarzana, CA 91356 Contact: Eve
                          Zisman (818) 345-2172 OPEN 940315.
CALIFORNIA                UCSD / Center for Special Immunology 2918
                          Fifth Ave / Suite 300 San Diego, CA 92103
                          Contact: Dr Scott Loss (619) 543-8080 OPEN
                          940315.
CALIFORNIA                UCI Medical Center Building 53 Route 81 / 101
                          City Drive South Orange, CA 92668 Contact:
                          Josephine Mosquara (714) 456-7612 OPEN
                          940315.
CALIFORNIA                California Medical Research Group 8636 North
                          First Street / Suite 120 Fresno, CA 93726
                          Contact: Margaret Northrop (209) 221-1327
                          OPEN 940315.
CALIFORNIA                ACRC AIDS Community Research Consortium 1048
                          El Camino Real / Suite A Redwood City, CA
                          94063 Contact: Deborah Harriss (415) 364-6564
                          OPEN 940315.
CALIFORNIA                ViRx Medical Group 1375 Sutter Street Suite
                          407 San Francisco, CA 94102 Contact: Joyce
                          Amann (415) 474-4440 OPEN 940315.
CALIFORNIA                St Francis Hospital / Clinical Research 909
                          Hyde Street San Francisco, CA 94109 Contact:
                          Max Huckabee (415) 353-6299 OPEN 940315.
CALIFORNIA                Davies Medical Center / Institute for HIV
                          Treatment and Rsch Castro and Duboce Streets
                          San Francisco, CA 94114 Contact: Sue Kelly
                          (415) 565-6153 OPEN 940315.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue /
                          Suite 235 Berkeley, CA 94705 Contact: Sherry
                          Lyman (510) 204-1870 Contact: Dr Carol
                          Brosgart (510) 204-1201 OPEN 940315.
CALIFORNIA                U of CA / Davis Med Ctr / AIDS and Related
                          Disorders Clinic 2221 Stockton Blvd / PCC Rm
                          3107 Sacramento, CA 95817 Contact: Sheila
                          Enders (916) 734-7004 OPEN 940315.
COLORADO                  University Hospital / Univ of Colorado Health
                          Sci Ctr Box B-163 / 4200 East Ninth Avenue
                          Denver, CO 80262 Contact: Graham Ray (303)
                          270-8551 OPEN 940315 ACTU: 0105.
DISTRICT OF COLUMBIA      Georgetown University / Medical Center 3800
                          Reservoir Road Washington, DC 20007 Contact:
                          Sara Swartzendruber (202) 687-1079 OPEN
                          940315.
DISTRICT OF COLUMBIA      George Washington University / Medical
                          Faculty Associates 2150 Pennsylvania Avenue /
                          Suite 5-419 Washington, DC 20037 Contact:
                          Barbara Lewis (202) 994-2417 OPEN 940315.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue 1st Floor Eliot Building
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 OPEN 940315.
FLORIDA                   Caremark Incorporated 3345 Burns Road / Suite
                          302 Palm Beach Gardens, FL 33410 Contact:
                          Unspecified (407) 775-7544 OPEN 940315.
FLORIDA                   St Josephs Hospital / Infectious Disease
                          Research Institute 4600 N Habana Ave / Suite
                          14 Tampa, FL 33614 Contact: Allis Emmett
                          (813) 870-4760 OPEN 940315.
GEORGIA                   Southeast Clinical Resources 1758 A Century
                          Boulevard Atlanta, GA 30345 Contact: Kym
                          Prieto (404) 325-4677 OPEN 940315.
IOWA                      University of Iowa 200 Hawkins Drive /
                          Southwest 54 GH Iowa City, IA 52242 Contact:
                          Unspecified (319) 356-3168 OPEN 940315.
ILLINOIS                  Rush Presbyterian / St Luke's Medical Center
                          Room 140 - 143 Academic Facility / 600 South
                          Paulina Chicago, IL 60612 Contact: Marilyn
                          Ashmann (312) 942-5865 OPEN 940315.
ILLINOIS                  University of Illinois 840 South Wood Street
                          Chicago, IL 60612 Contact: Unspecified (312)
                          996-6732 OPEN 940315.
INDIANA                   Infectious Diseases Research Clinic 550 N
                          University Blvd / Room 5550 Indianapolis, IN
                          46202 Contact: Jean Craft (317) 274-8456 OPEN
                          940315.
KANSAS                    University of Kansas School of Med /
                          University Hospital 39th at Rainbow Kansas
                          City, KS 66160-7354 Contact: Jane Harms (913)
                          588-6035 Contact: (913) 588-3896 OPEN 940315.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 940315.
KENTUCKY                  University of Kentucky Medical Center 800
                          Rose Street / Room MN633A Lexington, KY 40536
                          Contact: Karen Bowen (606) 257-5473 OPEN
                          940315.
LOUISIANA                 Tulane University Medical School / AIDS
                          Clinical Trials Unit 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Russell
                          Strada (504) 584-3605 OPEN 940315.
MASSACHUSETTS             Baystate Medical Center / Infectious Disease
                          Division 759 Chestnut Street Springfield, MA
                          01199 Contact: Deborah Prescod (413) 784-3046
                          OPEN 940315.
MASSACHUSETTS             University of Massachusetts Medical School 55
                          Lake Avenue North / Div Infectious Diseases
                          Worcester, MA 01655 Contact: Joan L Avto
                          (508) 856-2456 Contact: (508) 856-2666 OPEN
                          940315 ACTU: 3001.
MASSACHUSETTS             Massachusetts General Hospital Gray 5 /
                          Infectious Disease Unit Boston, MA 02114
                          Contact: Ellen Godfrey (617) 726-5598
                          Contact: Teri Flynn (617) 726-3819 OPEN
                          940315.
MASSACHUSETTS             Brigham Women's Hospital / Infectious Disease
                          Division 75 Francis Street Boston, MA 02115
                          Contact: Ann Elperin (617) 732-5885 OPEN
                          940315.
MASSACHUSETTS             Boston City Hospital / FGH-1 818 Harrison
                          Avenue / Thorndike Room 209 Boston, MA 02118
                          Contact: Nancy Reinhalter (617) 534-5404 OPEN
                          940315.
MASSACHUSETTS             New England Deaconess Hospital 185 Pilgrim
                          Road Boston, MA 02215 Contact: Helen Fitch
                          (617) 735-0785 OPEN 940315 ACTU: 0103.
MAINE                     AIDS Consultation Service / Maine Medical
                          Center 22 Bramhall Street Portland, ME 04102
                          Contact: Sandy Putnam (207) 871-2995 OPEN
                          940315.
MARYLAND                  University of Maryland / SOM / Department of
                          Med / Adult HIV Box 165 / 22 S Green Street
                          Baltimore, MD 21201 Contact: Andrea Fisch
                          (410) 706-1806 OPEN 940315.
MICHIGAN                  University of Michigan / Division of
                          Infectious Diseases 3116 B Taubman Center Ann
                          Arbor, MI 48109 Contact: unspecified (313)
                          936-5205 OPEN 940315.
MICHIGAN                  Harper Hospital Harper Professional Bldg /
                          Suite 202 / 4160 John R Detroit, MI 48201
                          Contact: Dr Crane (313) 745-9131 OPEN 940315.
MICHIGAN                  Henry Ford Hospital / Infectious Diseases
                          2799 West Grand Blvd / CFP 111 Detroit, MI
                          48202 Contact: Ann Marie Krystoforsky (313)
                          876-2798 OPEN 940315.
MINNESOTA                 St Paul Ramsey Medical Center / HIV Program
                          Office 640 Jackson Street St Paul, MN 55101
                          Contact: Holly Melroe (612) 221-1280 OPEN
                          940315.
MISSOURI                  Washington University Clinical Trials Unit
                          4511 Forest Park Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0058 OPEN
                          940315.
MISSOURI                  University of Missouri Kansas City / School
                          of Medicine 2411 Holmes Kansas City, MO 64108
                          Contact: Donna Simpson (816) 556-3478 OPEN
                          940315.
NORTH CAROLINA            University of NC / School of Medicine / Div
                          Infec Diseases 547 Burnett Womack Building /
                          CB7030 Chapel Hill, NC 27599-7030 Contact:
                          Barbara Longmeyer (919) 966-7883 OPEN 940315.
NORTH CAROLINA            Duke University Medical Center / Infectious
                          Diseases Clinic PO Box 3284 Durham, NC 27710
                          Contact: Ken Ship (919) 684-5260 OPEN 940315.
NORTH CAROLINA            Carolinas Medical Center / Department of
                          Internal Medicine 1000 Blythe Blvd AHEC Room
                          507 Charlotte, NC 28203 Contact: Joan Connell
                          (704) 355-5292 Contact: (704) 355-3165 OPEN
                          940315 ACTU: 3204.
NEBRASKA                  University of Nebraska Medical Center / HIV
                          Clinic 600 South 42nd Street Omaha, NE
                          68198-5130 Contact: Colleen R Kelly (402)
                          559-8163 OPEN 940315.
NEW JERSEY                Jersey Shore Medical Center 1945 Route #33
                          Neptune, NJ 07754 Contact: Susan Bataille
                          (908) 776-4700 OPEN 940315.
NEW YORK                  CRIA of New York 275 Seventh Avenue / 20th
                          Floor New York, NY 10001 Contact: Bette Smith
                          (212) 924-3934 OPEN 940315.
NEW YORK                  Beth Israel Medical Center / Department of
                          Medicine First Avenue and 16th Street New
                          York, NY 10003 Contact: Alice Fox (212)
                          420-4519 OPEN 940315.
NEW YORK                  St Vincents Hospital and Medical Center 412
                          Sixth Ave / 4th Floor New York, NY 10011
                          Contact: Noel George (212) 604-7625 OPEN
                          940315.
NEW YORK                  St Luke / Roosevelt Hospital Center / Dir HIV
                          / AIDS CTP 428 West 59th Street New York, NY
                          10019 Contact: Julie Rivera (212) 523-6723
                          OPEN 940315.
NEW YORK                  New York Hospital / Cornell Medical Center
                          505 East 70th Street New York, NY 10021
                          Contact: Paul Douglas (212) 746-4177 OPEN
                          940315.
NEW YORK                  Mount Sinai Hospital / Clinical Trials Unit 1
                          Gustave Levy Place New York, NY 10029
                          Contact: Eileen Chusid (212) 241-0433 OPEN
                          940315.
NEW YORK                  Westchester County Medical Center /
                          Department of Infec Dis 209 South East / Macy
                          Pavillion Valhalla, NY 10595 Contact: Gilda
                          Forseter (914) 285-1561 Contact: Diane
                          Holmgren (914) 285-7400 Contact: Dr Marissa
                          Montecalvo (914) 285-8865 Contact: Dr Gary
                          Wormser (914) 285-8865 OPEN 940315.
NEW YORK                  SUNY at Stony Brook Health Sciences Center /
                          Div Infect Dis HSC T 15 Room 080 Stony Brook,
                          NY 11794-8153 Contact: Ruth Ann Burk (516)
                          444-1658 OPEN 940315.
NEW YORK                  Albany Medical College / Div Med Oncology 47
                          New Scotland Avenue / Div Med Oncology A52
                          Albany, NY 12208-6752 Contact: Patricia
                          Amsler (518) 262-6759 OPEN 940315 ACTU: 7401.
NEW YORK                  SUNY at Buffalo / Erie County Medical Center
                          462 Grider Street Buffalo, NY 14215 Contact:
                          David Meger (716) 898-4482 OPEN 940315.
NEW YORK                  Community Health Network 758 South Avenue
                          Rochester, NY 14620 Contact: Lorraine Newcomb
                          (716) 244-9000 OPEN 940315.
NEW YORK                  University of Rochester Medical Center 601
                          Elmwood Avenue / Box 689 Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 940315.
OHIO                      University of Cincinnati Medical Center /
                          Holmes Division Eden and Bethesda Avenues
                          Cincinnati, OH 45267 Contact: Jill Leonard
                          (513) 558-8373 OPEN 940315.
OREGON                    Research and Education Group 2701 NW Vaughn
                          Streets / 770 Portland, OR 97210 Contact:
                          Sallie Israelit (503) 229-8428 OPEN 940315.
OTHER                     University of Puerto Rico / Department of
                          Medicine Medical Science Center / Room A 838
                          San Juan, PR 00936 Contact: Unspecified (809)
                          754-3755 OPEN 940315.
PENNSYLVANIA              University of Pittsburgh / School of Medicine
                          3515 Fifth Avenue Pittsburgh, PA 15261
                          Contact: Rosella Rosener (412) 647-8125 OPEN
                          940315.
PENNSYLVANIA              Pennsylvania State University / Hershey
                          Medical Center 500 Univ Drive / PO Box 850 /
                          Biomedical Rsrch Bldg C-6833 Hershey, PA
                          17033 Contact: Francine Damianos (717)
                          531-7488 OPEN 940315.
PENNSYLVANIA              University of Pennsylvania / Dept of Infect
                          Dis / HIV Clinic 536 Johnson Pavilion / 6073
                          Philadelphia, PA 19104 Contact: Heidi Lehman
                          (215) 662-6932 OPEN 940315.
PENNSYLVANIA              Childrens Hospital of Philadelphia / Division
                          of General Ped 34th Street and Civic Center
                          Boulevard / 2nd Floor Room 2015 Philadelphia,
                          PA 19104 Contact: Dr Richard Rutstein (215)
                          590-1466 OPEN 940315.
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 940315.
PENNSYLVANIA              Oncology and Hematology Association 1840
                          South Street / 2nd Floor Philadelphia, PA
                          19146 Contact: Barbara Rensman (215) 893-7541
                          OPEN 940315.
RHODE ISLAND              Memorial Hospital of Rhode Island 111
                          Brewster Street Pawtucket, RI 02860 Contact:
                          Francis Betencourt (401) 729-2918 OPEN
                          940315.
SOUTH CAROLINA            Medical University of South Carolina 171
                          Ashley Avenue Charleston, SC 29425 Contact:
                          Unspecified (803) 792-4541 OPEN 940315.
 
95
UNIQUE IDENTIFIER         FDA/00646
PROTOCOL ID NUMBERS       FDA 227B
PROTOCOL TITLE            A Randomized, Open-Label Trial of High Dose
                          Atovaquone Versus Low Dose Atovaquone Versus
                          Aerosolized Pentamidine for Prophylaxis of
                          Pneumocystis carinii Pneumonia in Patients
                          With HIV Infection Who Are Intolerant of
                          TMP/SMX.
VERSION NUMBER & DATE     (940802)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To assess whether high dose or low
                          dose atovaquone suspension is more effective
                          than aerosolized pentamidine as prophylaxis
                          against Pneumocystis carinii pneumonia (PCP)
                          in high-risk HIV-infected patients. To
                          compare the safety of chronic administration
                          of the three regimens in patients with
                          advanced HIV disease. To determine the
                          relationship between steady state atovaquone
                          plasma concentrations and prophylactic
                          efficacy against PCP. Methodology: Patients
                          are randomized to receive oral atovaquone at
                          either 1500 or 750 mg once daily or
                          aerosolized pentamidine at 300 mg once every
                          4 weeks. Treatment continues until 18 months
                          after the last patient is enrolled. Patients
                          are stratified into primary or secondary
                          prophylaxis strata based on prior occurrence
                          of a PCP episode.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive oral atovaquone at either 1500 or 750
                          mg once daily or aerosolized pentamidine at
                          300 mg once every 4 weeks. Treatment
                          continues until 18 months after the last
                          patient is enrolled. Patients are stratified
                          into primary or secondary prophylaxis strata
                          based on prior occurrence of a PCP episode.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940501)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive by ELISA or
                          Western blot. 2. Prior PCP (histologically
                          confirmed) OR documented CD4 count < 200
                          cells/mm3 OR constitutional symptoms such as
                          thrush or unexplained fever (> 100 F) for 2
                          or more weeks. 3. No current or suspected
                          active PCP, and no signs of active PCP on
                          chest x-ray. 4. Prior intolerance to TMP/SMX
                          or other trimethoprim or sulfa-containing
                          regimens.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Randomized; Open Label; Dose Comparison; Drug
                          Comparison; Multicenter; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Primary prophylaxis, Secondary
                          prophylaxis, Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 615 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until 18 months
                          after enrollment of last patient.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV positivity. 2. Prior PCP
                          (histologically confirmed) OR documented CD4
                          count < 200 cells/mm3 OR constitutional
                          symptoms such as thrush or unexplained fever
                          (> 100 F) for 2 or more weeks. 3. No current
                          or suspected active PCP, and no signs of
                          active PCP on chest x-ray. 4. Prior
                          intolerance to TMP/SMX or other trimethoprim
                          or sulfa-containing regimens. 5.
                          Life-expectancy of at least 6 months. NOTE:
                          Pregnant women are eligible at the discretion
                          of the investigator. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.0 g/dl. (Transfusion
                          permitted).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 80000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          (Patients who qualify for study entry based
                          on CD4 count alone must have < 200
                          cells/mm3). ( 0 - 100 ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Serum amylase < 2 x ULN. Absolute
                          neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Transfusion.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Antimicrobial
                          agents not specifically prohibited.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of severe or intractable intolerance
                          to atovaquone or aerosolized pentamidine. 2.
                          Prior hypoglycemia, pancreatitis,
                          arrhythmias, or severe hypotension associated
                          with any form of pentamidine. 3. Prior
                          enrollment in this protocol. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active substance abuse that
                          would preclude study compliance.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Rifampin.
                          2. Other investigational agents except for
                          drugs available through Treatment INDs or
                          expanded access programs. 3. Medications
                          likely to have anti-pneumocystis effect
                          (e.g., dapsone, trimethoprim, pyrimethamine,
                          trimetrexate, other DHFR inhibitors,
                          sulfadiazine, sulfamethoxazole, other
                          sulfonamides, primaquine, clindamycin, and
                          sulfonylureas. 4. Corticosteroids in greater
                          than physiologic replacement doses for more
                          than 21 consecutive days. 5. Systemic therapy
                          for CNS toxoplasmosis, Kaposi's sarcoma,
                          lymphoma, other active malignancies, or other
                          disease that may decrease life expectancy or
                          confound assessment.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Significant psychosis or emotional disorder
                          that would preclude study compliance. 2.
                          Severe chronic diarrhea (e.g., > five
                          stools/day) that may negatively affect
                          absorption of oral medication. 3. Unable to
                          take oral medication or unable or unwilling
                          to take medication with food.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0084  Atovaquone
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0025  Pentamidine
TRADE NAME OF SUBSTANCE   Drug 1 Mepron
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Lisa Behrens (800) 722-9292 X 3633.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1500 or 750 mg once
                          daily with a meal, for 78 weeks. Drug 2: 300
                          mg q 4 weeks over a 78-week period,
                          administered vinebulizer at a flow rate of
                          5-7 l/min over 30-45 min
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1500 or 750 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2:
                          Inhalation
OTHER TREATMENT INFO.     TREATMENT DURATION: Until 18 months after
                          enrollment of last patient.
OTHER TREATMENT INFO.     END POINT: Primary: Occurrence of
                          breakthrough PCP (including both
                          histologically confirmed or presumed PCP and
                          histologically confirmed extrapulmonary P.
                          carinii infection). Secondary: Dose-limiting
                          adverse effects, death.
SUPPORTING AGENCY         Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antifungal Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Naphthoquinones/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Pentamidine/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *PREVENTION & CONTROL
CAS REGISTRY NUMBER       0 (Antifungal Agents)
CAS REGISTRY NUMBER       100-33-4 (Pentamidine)
CAS REGISTRY NUMBER       94015-53-9 (atovaquone)
LAST REVISION DATE        940501
ENTRY MONTH               9408
FLORIDA                   Dr Goodgame and Hopkins 340 N Maitland Avenue
                          Maitland, FL 32751 Contact: Chuck DeMarzo
                          (407) 647-6000 OPEN 940802.
FLORIDA                   Bay Area AIDS Consortium 2901 Swann Avenue /
                          Suite 107 Tampa, FL 33609 Contact: Clinical
                          Trials Director (813) 877-5696 OPEN 940802.
NEW YORK                  St Vincent's Hospital AIDS Center 412 Sixth
                          Avenue / 4th Floor New York, NY 10011
                          Contact: Kerry McIntyre (212) 741-0784 OPEN
                          940802.
OHIO                      Holmes Hospital Eden and Bethesda Avenues
                          Cincinnati, OH 45267-0405 Contact: Dr Michael
                          Dohn (513) 558-6977 OPEN 940802.
 
96
UNIQUE IDENTIFIER         FDA/00668
PROTOCOL ID NUMBERS       FDA 226D
PROTOCOL TITLE            Phase I Study of the Clinical Pharmacology of
                          Azithromycin in Buffy Coat of HIV-Infected
                          Subjects.
VERSION NUMBER & DATE     (940927)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To compare the uptake of
                          azithromycin in white cells relative to
                          plasma concentrations in HIV-infected
                          patients. Methodology: Patients are
                          randomized to receive azithromycin orally or
                          intravenously, with crossover to the
                          alternate treatment after a 21-day wash-out
                          period.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive azithromycin orally or intravenously,
                          with crossover to the alternate treatment
                          after a 21-day wash-out period.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940801)
DISEASE STUDIED           Bacterial infections.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by Western
                          blot confirmed by ELISA. 2. CD4 count <= 200
                          cells/mm3. 3. No active AIDS-defining
                          opportunistic infection (unless discussed
                          with Pfizer Clinician).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-062
STUDY DESIGN              Open Label; Randomized; Crossover;
                          Comparative administration route
PROTOCOL DETAILS          STUDY INTENT: Pharmacokinetics,
                          Administration route comparison.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count <= 200
                          cells/mm3. 3. No active opportunistic
                          infection (pending discussion with Pfizer
                          Clinician). [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 200 cells/mm3. ( 0 -
                          100 - 200 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 75 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 3 x ULN.
                          Absolute neutrophils > 750 cells/mm3.
                          Negative urine drug screen. Negative ethanol
                          breath test.
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior
                          antiretroviral agents.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Antiretroviral agents, provided regimen has
                          been stable for at least 1 month.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of clinically signficant allergic,
                          hematological, renal, endocrine, pulmonary,
                          gastrointestinal, cardiovascular, hepatic,
                          psychiatric, or neurological disease. 2.
                          Clinically important change in baseline
                          status within 4 weeks prior to study entry.
                          3. Condition affecting drug absorption (e.g.,
                          ulcers, gastrectomy, HIV-associated
                          enteropathies) within 4 weeks prior to study
                          entry. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control during study and for 90 days
                          after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Known drug or alcohol
                          dependence.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Investigational
                          drugs including treatment IND drugs within 4
                          weeks prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active intercurrent illness (pending
                          discussion with the Pfizer Clinician). 2.
                          Allergies to macrolide antibiotics. 3. Signs
                          and symptoms of severe illness that would
                          preclude treatment.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
TRADE NAME OF SUBSTANCE   Drug 1 Zithromax
MANUFACTURERS             Drug 1: Pfizer Central Research Eastern Point
                          Road Groton, CT 06340 Contact: Dr Aron Stein
                          (203) 441-6106.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1200 mg per
                          treatment
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral and intravenous
                          (IV)
SUPPORTING AGENCY         Pfizer Central Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Azithromycin/ADMINISTRATION & DOSAGE/
                          *PHARMACOKINETICS
MESH HEADING              Bacterial Infections/COMPLICATIONS/
                          *PREVENTION & CONTROL
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        940801
ENTRY MONTH               9409
KANSAS                    Center for Phase I Research 1100 North St
                          Francis / Suite 200 Wichita, KS 67214
                          Contact: Dr Donna Sweet (316) 268-5984 OPEN
                          940801.
 
97
UNIQUE IDENTIFIER         FDA/00660
PROTOCOL ID NUMBERS       FDA 226C
PROTOCOL TITLE            Double-Blind Crossover Study Assessing the
                          Dose Proportionality of Azithromycin Tablets
                          in HIV-Infected Subjects.
VERSION NUMBER & DATE     (940909)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To assess the dose proportionality
                          of azithromycin concentrations and toleration
                          when delivered in tablet formulation to
                          HIV-infected patients.
GENERAL DESCRIPTION       RATIONALE: The need exists to further assess
                          the antibacterial agent azithromycin at
                          differing doses in an HIV-infected
                          population.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive azithromycin at 600 or 1200 mg in a
                          two-treatment, two-period, cross-over study.
                          Dosing visits are separated by at least
                          14-day wash-out periods.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940601)
DISEASE STUDIED           Bacterial infections.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by Western
                          blot and ELISA. 2. CD4 count <= 500
                          cells/mm3. 3. NO active AIDS opportunistic
                          infection.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    066-060
STUDY DESIGN              2-Arm; Double-Blind; Dose Comparison;
                          Crossover; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug dosing schedule, Drug
                          tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 12 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. CD4 count <=
                          500 cells/mm3. 3. NO active AIDS
                          opportunistic infection. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 500 cells/mm3. ( 0 -
                          100 - 200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 75 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 750 cells/mm3.
                          Alkaline phosphatase < 3 x ULN. Negative
                          urine drug screen and blood alcohol test.
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          Clinically important change in baseline
                          status within 4 weeks prior to study entry.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Known drug or alcohol
                          dependence.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Investigational
                          drugs including treatment IND drugs within 4
                          weeks prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Other
                          active intercurrent illness. 2. Any condition
                          possibly affecting drug absorption (e.g.,
                          ulcers, gastrectomy, HIV-associated
                          enteropathies. 3. Signs or symptoms of severe
                          illness that would preclude study
                          participation. 4. Known allergies to
                          macrolide antibiotics.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
MANUFACTURERS             Drug 1: Pfizer Central Research Eastern Point
                          Road Groton, CT 06340 Contact: Dr Aron Stein
                          (203) 441-6106.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 600 or 1200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, tablets
SUPPORTING AGENCY         Pfizer Central Research.
MESH HEADING              Adult
MESH HEADING              Azithromycin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS
MESH HEADING              Bacterial Infections/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        940601
ENTRY MONTH               9409
ARIZONA                   Harris Laboratories Inc 4639 South 36th
                          Street Phoenix, AZ 85040 Contact: Dr Wayne
                          Colburn (602) 437-0097 OPEN 940909.
 
98
UNIQUE IDENTIFIER         FDA/00673
PROTOCOL ID NUMBERS       FDA 226B
PROTOCOL TITLE            A Randomized, Double-Blind, Comparative Study
                          of Azithromycin Versus Clarithromycin in
                          Combination with Ethambutol for the Treatment
                          of Disseminated Mycobacterium Avium Complex
                          (MAC).
VERSION NUMBER & DATE     (940323)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy and safety
                          of two different doses of azithromycin in
                          combination with ethambutol for the treatment
                          of patients with Mycobacterium Avium Complex
                          (MAC) infection, and to determine whether an
                          azithromycin-containing regimen is at least
                          as safe and effective as the same regimen
                          containing clarithromycin. Methodology:
                          Patients are randomized to receive
                          azithromycin at one of two doses in
                          combination with ethambutol or clarithromycin
                          in combination with ethambutol for 24 weeks,
                          after which they are evaluated for entry into
                          a maintenance phase of treatment. Clinical,
                          microbiologic, and safey assessments are
                          performed every 3 weeks for the first 12
                          weeks, then monthly for the remaining 12
                          weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive azithromycin at one of two doses in
                          combination with ethambutol or clarithromycin
                          in combination with ethambutol for 24 weeks,
                          after which they are evaluated for entry into
                          a maintenance phase of treatment. Clinical,
                          microbiologic, and safey assessments are
                          performed every 3 weeks for the first 12
                          weeks, then monthly for the remaining 12
                          weeks.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940728)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA
                          and/or Western blot and/or PCR. 2.
                          Disseminated MAC by positive blood culture
                          within 2 months prior to study entry. 3. No
                          MAC therapy between time of last positive
                          blood culture draw and study entry
                          (single-agent prophylaxis allowed).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-189. 189/189B
STUDY DESIGN              Randomized; Double-Blind; Comparative; Drug
                          Combination; Dose Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. Disseminated
                          MAC. 3. No MAC therapy between time of last
                          positive blood culture draw and study entry
                          (single-agent prophylaxis allowed). 4. Life
                          expectancy of at least 2 months. 5. Consent
                          of parent or guardian if below legal age of
                          consent. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 3.0.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control during study and for 90 days
                          after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: MAC therapy
                          between time of last positive blood culture
                          draw and study entry (although single-agent
                          prophylaxis is allowed).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Another
                          investigational drug started in the week
                          prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          hypersensitivity to macrolide antibiotics
                          (erythromycin, azithromycin, or
                          clarithromycin) or ethambutol. 2. Inability
                          to take oral medications. 3. Condition likely
                          to interfere with drug absorption (e.g.,
                          gastrectomy, malabsorption syndromes).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0099  Clarithromycin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0104  Azithromycin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0111  Ethambutol
TRADE NAME OF SUBSTANCE   Drug 2 Zithromax
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 2: Pfizer Central Research Eastern Point
                          Road Groton, CT 06340 Contact: Dr Aron Stein
                          (203) 441-6106.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 500 mg BID for 24
                          weeks. Drug 2: 250 or 600 mg daily for 24
                          weeks. Drug 3: 800 mg (if < 65 kg) or 1200 mg
                          (if >= 65 kg) daily for weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1000 mg. Drug 2: 250 or
                          600 mg. Drug 3: 800 or 1200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 24 weeks.
SUPPORTING AGENCY         Pfizer Central Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Clarithromycin/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       81103-11-9 (Clarithromycin)
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        940728
ENTRY MONTH               9410
CALIFORNIA                University of California Irvine / Dept of Med
                          / Infect Disea 101 City Drive South /
                          Building 53 / Route 53 Orange, CA 92668
                          Contact: Bobi Keenan (714) 456-7612 OPEN
                          941103.
CALIFORNIA                HIV Research Unit / Kaiser Permanente Medical
                          Group 2590 Geary Boulevard San Francisco, CA
                          94115 Contact: Joe Thatcher (415) 202-3480
                          Contact: Dr W Jeffrey Fessel OPEN 941103.
CALIFORNIA                Infectious Disease Medical Gp / Adult
                          Immunology Clinic 3012 Summit Street Sixth
                          Floor Oakland, CA 94609 Contact: Jamie
                          Carroll (510) 420-6014 Contact: Doctors
                          office (510) 834-2800 OPEN 941103.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue
                          Suite 235 Berkeley, CA 94705 Contact: Nancy
                          Orcutt (510) 204-1291 OPEN 940915.
CALIFORNIA                Santa Clara Valley Medical Center / AIDS
                          Program 751 South Bascom Avenue San Jose, CA
                          95128-2699 Contact: Carol Kane (408) 885-4316
                          Contact: Dr Carol Kemper (assoc dir) (408)
                          885-4300 OPEN 940915.
DISTRICT OF COLUMBIA      Georgetown University 110 Kober-Cogan
                          Building / 3800 Reservoir Road Northwest
                          Washington, DC 20007-2197 Contact: Sharon
                          Boone (202) 687-7387 Contact: Dr Princy Kumar
                          (202) 687-6845 OPEN 941103.
DISTRICT OF COLUMBIA      Whitman Walker Clinic 1701 NW 14th Street
                          Washington, DC 20009 Contact: Christiane
                          Jones (202) 745-6151 OPEN 940915.
FLORIDA                   Medical Service (111-1) 1201 NW 16 Street
                          Miami, FL 33125 Contact: Karen Cleven (305)
                          324-3267 Contact: Tommie Stapleton (305)
                          324-3267 Contact: Dr Gordon Dickinson (305)
                          324-3267 OPEN 941103.
FLORIDA                   Bay Area AIDS Consortium 2901 Swann Avenue /
                          Suite 107 Tampa, FL 33609 Contact: Clinical
                          Trials Director (813) 877-5696 OPEN 940728.
FLORIDA                   Dr Robert Wallace 2663 First Avenue North St
                          Petersburg, FL 33713 Contact: Becky Tarbett -
                          key contact (813) 877-5696 Contact: (Bay Area
                          AIDS Consortium) Contact: Doctor's office
                          (813) 327-5188 OPEN 940915.
ILLINOIS                  Northwestern Univ Medical School / Comp AIDS
                          Ctr / Infec Dis 303 East Superior Street /
                          Passavant Room 823 Chicago, IL 60611 Contact:
                          Baiba Berzins (312) 908-9636 OPEN 940915.
ILLINOIS                  Dr Neel French / Louis A Weiss Memorial
                          Hospital 4640 North Marine Drive Suite 4
                          Chicago, IL 60640 Contact: Dr Neel French
                          (312) 275-2562 OPEN 941103.
MISSOURI                  Trinity Lutheran Hospital / Infectious
                          Disease Clinic 3030 Baltimore Kansas City, MO
                          64108 Contact: Maithe E. Fowler (816)
                          751-2792 Contact: (816) 751-2332 OPEN 940915.
 
99
UNIQUE IDENTIFIER         FDA/00609
PROTOCOL ID NUMBERS       FDA 226A
PROTOCOL TITLE            A Randomized Study of Daily and Intermittent
                          Prophylactic Regimens for the Prevention of
                          Disseminated Mycobacterium avium Complex
                          (MAC) and Fungal Infections in HIV-Infected
                          Patients.
VERSION NUMBER & DATE     (940323)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To determine the efficacy
                          of azithromycin and rifabutin alone and in
                          combination for the prevention of
                          disseminated Mycobacterium avium Complex
                          (MAC) infection in HIV-infected patients. To
                          determine the efficacy of daily versus weekly
                          fluconazole for the prevention of deep fungal
                          infections in this patient population.
                          SECONDARY: To determine the incidence of
                          bacterial (including mycobacterial)
                          infections, cryptosporidiosis, and
                          toxoplasmosis in azithromycin versus
                          non-azithromycin containing regimens. To
                          determine the incidence of oropharyngeal and
                          vaginal candidiasis in patients treated with
                          daily versus weekly fluconazole. To compare
                          survival and outcomes of primary endpoints in
                          the treatment arms. Methodology: Patients are
                          randomized to receive azithromycin alone,
                          rifabutin alone, or the two drugs in
                          combination for MAC prophylaxis. Patients in
                          each treatment group further receive one of
                          two doses of concomitant fluconazole for deep
                          fungal prophylaxis, unless specifically
                          excluded for fluconazole randomization.
                          Patients are followed for 1 to 2 years.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive azithromycin alone, rifabutin alone,
                          or the two drugs in combination for MAC
                          prophylaxis. Patients in each treatment group
                          further receive one of two doses of
                          concomitant fluconazole for deep fungal
                          prophylaxis, unless specifically excluded for
                          fluconazole randomization. Patients are
                          followed for 1 to 2 years.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (921201)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ), Fungal infections (Myco
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Laboratory evidence of HIV
                          infection or history of an AIDS-defining
                          condition by CDC criteria. 2. One documented
                          CD4 count < 100 cells/mm3 within 12 months
                          prior to study entry. 3. NO known or
                          disseminated MAC disease or MAC bacteremia or
                          active nontuberculous mycobacterial
                          infection. 4. NO known or suspected M.
                          tuberculosis infection. 5. Chest radiograph
                          within 1 month prior to study entry that
                          shows no evidence of active disease. 6. NO
                          acute opportunistic infection (although
                          patients receiving maintenance therapy for
                          CMV retinitis are permitted).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-174
STUDY DESIGN              Randomized; Double-Blind; Multicenter; Drug
                          Comparison; Dose Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug
                          efficacy, Combination drug therapy,
                          Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 720 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 12 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection or history of an
                          AIDS-defining condition by CDC criteria. 2.
                          One documented CD4 count < 100 cells/mm3
                          within 12 months prior to study entry. 3. NO
                          active MAC disease, MAC bacteremia, or active
                          mycobacterial infection (tuberculous or
                          nontuberculous). 4. NO acute opportunistic
                          infection. 7. Life expectancy of more than 6
                          months. 8. Consent of parent or guardian if
                          less than legal age of consent. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 100 cells/mm3. ( 0 ).
                          One documented count within 12 months prior
                          to study entry.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 3 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 500 cells/mm3.
PATIENT AGE               AGE: 12 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Preventive
                          therapy with isoniazid for M. tuberculosis.
                          2. Maintenance therapy for CMV retinitis.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 11 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded for
                          fluconazole randomization: 1. Maintenance
                          therapy for deep fungal infections. 2.
                          Chronic therapy with ketoconazole or
                          fluconazole.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: ALL
                          PATIENTS - 1. Unexplained fevers, elevation
                          in alkaline phosphatase, pancytopenia,
                          abnormal liver function tests, or odynophagia
                          for which the diagnoses of MAC and fungal
                          infections have not been excluded. 2. Serious
                          hypersensitivity reactions to macrolides or
                          rifampin. 3. Unable to tolerate oral
                          medications. FOR FLUCONAZOLE RANDOMIZATION -
                          1. Serious hypersensitivity reaction to
                          fluconazole. 2. Active fungal infection
                          (cryptococcosis, histoplasmosis,
                          blastomycosis, aspergillosis, Candida
                          esophagitis, thrush, vaginal candidiasis). 3.
                          Positive baseline urine cryptococcal culture.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0005  Fluconazole
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0085  Rifabutin
TRADE NAME OF SUBSTANCE   Drug 1 Zithromax
TRADE NAME OF SUBSTANCE   Drug 2 Diflucan
MANUFACTURERS             Drug 1: Pfizer Central Research Eastern Point
                          Road Groton, CT 06340 Contact: Dr Aron Stein
                          (203) 441-6106.
MANUFACTURERS             Drug 2: Pfizer Central Research Eastern Point
                          Road Groton, CT 06340 Contact: Dr Aron Stein
                          (203) 441-6106.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1200 mg weekly. Drug
                          2: 200 mg daily or 400 mg weekly. Drug 3: 300
                          mg daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 3: 300 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 600 mg
                          lactose-free tablets. Drug 2: Oral, 200 mg
                          tablets. Drug 3: Oral, 150 mg capsules
SUPPORTING AGENCY         Pfizer Central Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Fluconazole/ADMINISTRATION & DOSAGE/
                          *THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*PREVENTION & CONTROL
MESH HEADING              Mycoses/COMPLICATIONS/*PREVENTION & CONTROL
MESH HEADING              Rifabutin/*THERAPEUTIC USE
CAS REGISTRY NUMBER       72559-06-9 (Rifabutin)
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        921201
ENTRY MONTH               9403
CALIFORNIA                Los Angeles County / Univ of Southern
                          California Medical Ctr Building 5P21 / Room
                          349 / 1175 Cummings Street Los Angeles, CA
                          90033 Contact: Dr Michael Dube (213) 226-7504
                          OPEN 921201.
CALIFORNIA                Harbor UCLA Medical Center / Department of
                          Medicine 1000 West Carson Street Torrance, CA
                          90509 Contact: Sally Kruger (310) 222-3848
                          OPEN 921201.
CALIFORNIA                University of California / San Diego
                          Treatment Center 2760 Fifth Avenue / Suite
                          300 San Diego, CA 92103 Contact: Cathy Nuffer
                          (619) 543-8080 Contact: Dr Diane Havir (619)
                          543-8080 OPEN 921201.
CALIFORNIA                University of California Irvine / Dept of Med
                          / Infect Disea 101 City Drive South /
                          Building 53 / Route 53 Orange, CA 92668
                          Contact: Bobi Keenan (714) 456-7612 OPEN
                          921201.
CALIFORNIA                Santa Clara Valley Medical Center / AIDS
                          Program 751 South Bascom Avenue San Jose, CA
                          95128-2699 Contact: Carol Kane (408) 885-4316
                          Contact: Dr Carol Kemper (assoc dir) (408)
                          885-4300 OPEN 921201.
DISTRICT OF COLUMBIA      Georgetown University Medical Center 3800
                          Reservoir Rd / Kober-Cogan Bldg / Suite 100
                          Washington, DC 20007 Contact: Jeanne Trembeth
                          (202) 687-5378 OPEN 921201.
DISTRICT OF COLUMBIA      George Washington University / Medical Center
                          / Div Inf Dise 2150 Pennsylvania Ave NW
                          Washington, DC 20037 Contact: Susan
                          LeLacheruri (202) 994-2417 OPEN 921201.
MASSACHUSETTS             University of Massachusetts Medical School 55
                          Lake Avenue North / Div Infectious Diseases
                          Worcester, MA 01655 Contact: Joan L Avto
                          (508) 856-2456 Contact: (508) 856-2666 OPEN
                          921201 ACTU: 3001.
NEW YORK                  Memorial Sloan Kettering Cancer Center /
                          Cornell Medical Col 525 East 68th Street New
                          York, NY 10021 Contact: Trisha Seroko (212)
                          746-4177 Contact: Dr Kent Sepkowitz (212)
                          746-4177 OPEN 921201.
PENNSYLVANIA              University of Pennsylvania / Depart of
                          Infectious Diseases 6073 36th Street and
                          Hamilton Walk/536 Johnson Pavillion G2
                          Philadelphia, PA 19104 Contact: Amy Graziani
                          (215) 662-2900 OPEN 921201.
 
100
UNIQUE IDENTIFIER         FDA/00605
PROTOCOL ID NUMBERS       FDA 224A
PROTOCOL TITLE            Randomized Phase I Study of Trimetrexate
                          Glucuronate (TMTX) With Leucovorin (LCV)
                          Protection Plus Dapsone Versus Trimethoprim /
                          Sulfamethoxazole (TMP/SMX) for Treatment of
                          Moderately Severe Episodes of Pneumocystis
                          carinii Pneumonia.
VERSION NUMBER & DATE     (940713)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of the
                          combination of trimetrexate glucuronate
                          (TMTX) and dapsone with leucovorin protection
                          versus trimethoprim/sulfamethoxazole
                          (TMP/SMX) in patients with AIDS and
                          moderately severe Pneumocystis carinii
                          pneumonia (PCP). To determine the
                          pharmacokinetic parameters of TMTX,
                          leucovorin, and dapsone and of TMP/SMX when
                          given to patients with AIDS and moderately
                          severe PCP.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940124)
DISEASE STUDIED           Pneumocystis carinii pneumonia ( PCP ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS by CDC criteria. 2.
                          Confirmed diagnosis of PCP by morphologic
                          confirmation of three or more typical
                          Pneumocystis carinii organisms in sputum,
                          bronchoalveolar lavage fluid, or lung tissue
                          within 10 days prior to study entry. (If PCP
                          is highly suspected but diagnosis has not
                          been made, confirmation may be established
                          within the first 10 days of study.) 3.
                          Alveolar-arterial differences in dissolved
                          oxygen >= 35 mm Hg but < 55 mm Hg on room
                          air.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    TMTX A009
STUDY DESIGN              Prospective; Randomized; Double-Blind; Drug
                          Comparison; Drug Tolerance; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Combination drug
                          therapy, Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. Confirmed diagnosis of PCP.
                          3. Alveolar-arterial differences in dissolved
                          oxygen >= 35 mm Hg but < 55 mm Hg on room
                          air. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl. (Transfusion
                          permitted).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 14 days after.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Empiric
                          therapy for other opportunistic pulmonary
                          infection (TB or fungi) for the first 72
                          hours of study enrollment ONLY, until
                          presence of suspected pathogens can be
                          confidently excluded.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded: Prior
                          history of serious or life-threatening
                          intolerance to TMP/SMX. (NOTE: Patients with
                          less severe reactions may be included at the
                          discretion of the investigator and primary
                          care provider.) [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. No
                          abstinence or no agreement to use effective
                          method of birth control during study and for
                          14 days after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: More than 24
                          hours of systemic anti-PCP therapy within 2
                          weeks prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Induction
                          therapy with bone marrow suppressive drugs
                          (e.g., ganciclovir) or hepatotoxic drugs
                          (e.g., chemotherapy). 2. AZT, ddI, ddC, d4T,
                          or other antiretroviral therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Severe renal or hepatic dysfunction. 2.
                          Serious or life-threatening intolerance to
                          TMP/SMX, TMTX, or dapsone. 3. Concurrent
                          pneumothorax. 4. Active pulmonary
                          tuberculosis or other inadequately treated
                          opportunistic pulmonary infection (e.g.,
                          Cryptocococcus neoforms, CMV). NOTE:
                          Identification of Mycobacterium avium or CMV
                          in sputum or BAL fluid does not exclude,
                          since these organisms may be present without
                          causing disease. 5. Pulmonary Kaposi's
                          sarcoma. 6. Active opportunistic infections
                          or malignancies requiring induction therapy
                          with bone marrow suppressive drugs (e.g.,
                          ganciclovir) or hepatotoxic drugs (e.g.,
                          chemotherapy). 7. Unable to have arterial
                          blood gases on room air obtained at baseline.
                          8. Unwilling to undergo bronchoscopy, if
                          sputum induction does not reveal Pneumocystis
                          carinii. 9. Suspected malabsorption (e.g.,
                          ileus or severe diarrhea with > 6
                          stools/day). 10. Known absence of G6PD
                          activity. 11. Large volume (1.0 to 1.5
                          liters) of intravenous fluid (5 percent in
                          water) per 24 hours is medically inadvisable.
                          12. Unwilling to comply with study design.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0183  Trimetrexate glucuronate
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0002  Leucovorin calcium
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0036  Dapsone
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0030  Trimethoprim
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0031  Sulfamethoxazole
MANUFACTURERS             Drug 1: US Bioscience Incorporated One Tower
                          Bridge 100 Front Street West Conshohocken, PA
                          19428 Contact: Dr Edith Mitchell (610)
                          832-4525.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Jacobus Pharmaceutical Company PO Box
                          5290 / 37 Cleveland Lane Princeton, NJ 08540
                          Contact: Dr David Jacobus (609) 921-7447.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 5: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 days.
OTHER TREATMENT INFO.     END POINT: Survival; dose-limiting toxicity
                          at 10 days, completion of therapy (21 days
                          +/- 3 days), and 1 month following completion
                          of therapy; differences in arterial blood
                          gases (ABGs) after 10 and 21 days (+/- 3
                          days) of study therapy.
SUPPORTING AGENCY         US Bioscience Incorporated, Jacobus
                          Pharmaceutical Company.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Dapsone/*ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Leucovorin/PHARMACOKINETICS/*THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pneumonia, Pneumocystis carinii/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Trimethoprim-Sulfamethoxazole Combination/
                          *ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Trimetrexate/*ADVERSE EFFECTS/
                          PHARMACOKINETICS
CAS REGISTRY NUMBER       52128-35-5 (Trimetrexate)
CAS REGISTRY NUMBER       58-05-9 (Leucovorin)
CAS REGISTRY NUMBER       80-08-0 (Dapsone)
CAS REGISTRY NUMBER       8064-90-2 (Trimethoprim-Sulfamethoxazole
                          Combination)
LAST REVISION DATE        940124
ENTRY MONTH               9403
CALIFORNIA                University of Southern California Medical
                          Center 1175 N Cummings Street / Bldg 5P21 /
                          Room 349 Los Angeles, CA 90033 Contact: Diane
                          Ramos (213) 343-8288 OPEN 940124.
 
101
UNIQUE IDENTIFIER         FDA/00606
PROTOCOL ID NUMBERS       FDA 223A
PROTOCOL TITLE            Diethylhomospermine (DEHSPM) for Refractory
                          AIDS-Related Diarrhea.
VERSION NUMBER & DATE     (940222)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To perform preliminary clinical
                          testing of diethylhomospermine (DEHSPM), a
                          polyamine analog, for refractory AIDS-related
                          diarrhea.
GENERAL DESCRIPTION       RATIONALE: Possibly, DEHSPM will reduce stool
                          volume and frequency in patients with
                          refractory AIDS-related diarrhea.
GENERAL DESCRIPTION       METHODOLOGY: Patients are initially hydrated
                          for 24 hours, followed by a 3-day baseline
                          period. They then receive intravenous
                          infusions of DEHSPM three times per day for 3
                          days, followed by observation for 3 days.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940214)
DISEASE STUDIED           Diarrhea.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. ARC or AIDS by CDC criteria.
                          2. Uncontrolled diarrhea defined as more than
                          500 ml liquid stool daily for at least 4
                          weeks duration despite at least 2 weeks of
                          high-dose, nonspecific antidiarrheal therapy
                          (i.e., loperamide, diphenoxylate
                          hydrochloride-atropine sulfate, or opiates)
                          at maximally tolerable doses. NOTE: Patients
                          with cytomegalovirus colitis or enteritis are
                          permitted if they are unresponsive to
                          ganciclovir therapy. Patients with
                          Mycobacterium avium-intracellulare,
                          Cryptosporidium parvum, or microsporidial
                          infection are permitted only if they are
                          receiving no other experimental drugs. NOTE:
                          Patients must have none of the
                          gastrointestinal disorders that are
                          specifically excluded.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Open Label; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 10 days.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. ARC or AIDS by CDC criteria. 2.
                          Uncontrolled diarrhea unresponsive to
                          high-dose, nonspecific antidiarrheal therapy.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
                          Postmenopausal or infertile because of tubal
                          ligation, hysterectomy, bilateral
                          oophorectomy, or oral contraceptives.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: At least 2 weeks
                          of prior high-dose, nonspecific antidiarrheal
                          therapy (i.e., loperamide, diphenoxylate
                          hydrochloride-atropine sulfate, or opiates)
                          at maximally tolerable doses.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Reproductive
                          potential.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Other
                          experimental drugs within 1 month prior to
                          study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          experimental antidiarrheal drugs. 2.
                          Antibiotic therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          idiopathic ulcerative colitis or Crohn
                          colitis. 2. Acute stool-culture-positive
                          bacterial colitis. 3. Acute amoebic colitis.
                          4. Pseudomembranous colitis with Clostridium
                          difficile toxin positivity. 5. Short-gut
                          syndrome. 6. Chronic pancreatitis. 7.
                          Ischemic bowel disease. 8. Enteroenteric
                          fistulae. 9. Other gastrointestinal tract
                          disorders known to cause diarrhea. 10.
                          Underlying evidence of immunosuppression
                          other than that related to HIV infection. 11.
                          Unable or unwilling to have subcutaneous
                          injections. 12. Clinically significant CNS,
                          hepatic, or renal disease.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0203  Diethylhomospermine
TRADE NAME OF SUBSTANCE   Drug 1 DEHSPM
MANUFACTURERS             Drug 1: Gainesville Veterans Administration
                          Medical Center Gastroenterology Section 111-C
                          Gainesville, FL 32608 Contact: Dr Charles A
                          Sninsky (904) 374-6055.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 30 mg/m2 daily for 3
                          days
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 30 mg/m2
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV)
OTHER TREATMENT INFO.     TREATMENT DURATION: 3 days.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Development of
                          an excluded condition. 2. Requirement for
                          antibiotics.
SUPPORTING AGENCY         Gainesville Veterans Administration Medical
                          Center.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Antidiarrheals/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Diarrhea/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Spermine/ANALOGS & DERIVATIVES/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antidiarrheals)
CAS REGISTRY NUMBER       119422-08-1
                          (N(1),N(14)-bis(ethyl)homospermine)
LAST REVISION DATE        940214
ENTRY MONTH               9403
FLORIDA                   Gainesville Veterans Administration Medical
                          Center Gastroenterology Section 111-C
                          Gainesville, FL 32608 Contact: Dr Charles A
                          Sninsky (904) 374-6055 OPEN 940214.
 
102
UNIQUE IDENTIFIER         FDA/00604
PROTOCOL ID NUMBERS       FDA 222A
PROTOCOL TITLE            A Phase I/II Clinical Study of WF 10 IV
                          Solution (Oxoferin; TCDO) in Patients With
                          HIV Infection.
VERSION NUMBER & DATE     (940309)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the clinical toxicity,
                          safety, and MTD of oxoferin (WF 10; TCDO)
                          intravenous solution administered to patients
                          with HIV infection. To evaluate the potential
                          anti-HIV activity of TCDO.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940309)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive by ELISA. 2.
                          Absolute CD4 count of 150 - 500 cells/mm3 in
                          two determinations within 15 days prior to
                          study entry. 3. At least 6 months of prior
                          zidovudine therapy. 4. No active
                          opportunistic infection requiring ongoing
                          therapy.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    WF10-92-US-001
STUDY DESIGN              Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug toxicity,
                          Maximum tolerated dose (MTD), Drug efficacy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV positivity. 2. Absolute CD4
                          count of 150 - 500 cells/mm3. 3. At least 6
                          months of prior zidovudine therapy. 4. No
                          active opportunistic infection requiring
                          ongoing therapy. 5. Life expectancy of at
                          least 6 months. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 10 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: > 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 150 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.95 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3.0 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: > 70.
PATIENT INCLUSION CRIT.   OTHER: Normal PT and PTT.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: At least 6 months
                          of prior zidovudine.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: Aerosolized
                          pentamidine (300 mg monthly) as prophylaxis
                          for PCP only in patients with CD4 count <=
                          200 cells/mm3. Allowed: PCP prophylaxis with
                          aerosolized pentamidine in patients with CD4
                          count > 200 cells/mm3, only at the discretion
                          of the treating physician.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of myocardial infarction or
                          arrhythmias. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug or alcohol abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 weeks
                          prior to study entry: 1. Antiretroviral agent
                          or interferon. 2. Systemic biologic response
                          modifiers, corticosteroids, cytotoxic
                          chemotherapeutic agents, or other drugs that
                          can cause neutropenia or significant
                          nephrotoxicity. 3. Rifampin or rifampin
                          derivatives. 4. Systemic anti-infectives.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Neoplasm other than basal cell carcinoma of
                          the skin. 2. Clinically significant cardiac
                          disease. 3. Abnormal neurological status by a
                          standardized assessment including strength,
                          reflex testing, and sensory testing. 4.
                          Unwilling to comply with protocol
                          requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0204  Oxoferin
TRADE NAME OF SUBSTANCE   Drug 1 WF 10
MANUFACTURERS             Drug 1: Oxo Chemie GmbH Im Neuenheimer Feld
                          517 Heidelberg, GE Contact: Unspecified.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV),
                          solution
SUPPORTING AGENCY         Oxo Chemie GmbH.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADVERSE EFFECTS/THERAPEUTIC
                          USE
MESH HEADING              Chlorine/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Oxides/*ADVERSE EFFECTS/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       92047-76-2 (oxoferin)
LAST REVISION DATE        940309
ENTRY MONTH               9403
 
103
UNIQUE IDENTIFIER         FDA/00603
PROTOCOL ID NUMBERS       FDA 221A
PROTOCOL TITLE            A Randomized, Placebo-Controlled,
                          Double-Blind, Single and Multiple Oral
                          Dose-Tolerance Study of Oral MDL 28,574A
                          Solution in HIV-Positive Patients.
VERSION NUMBER & DATE     (940302)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To characterize the safety profile
                          of MDL 28574A following both acute and
                          subchronic dosing in HIV-positive patients.
                          To determine the MTD of both acute and
                          subchronic doses of this drug when
                          administered as oral solution. To determine
                          the pharmacokinetic profile of MDL 28574A and
                          castanospermine (from which MDL 28574A is
                          derived) following both acute and subchronic
                          dosing. Methodology: In Part A of the study,
                          patients receive a single oral dose of MDL
                          28574A on day 1 and are followed through day
                          7. In Part B, patients receive single daily
                          doses of the drug on days 1 through 14 and
                          are followed through day 21.
GENERAL DESCRIPTION       METHODOLOGY: In Part A of the study, patients
                          receive a single oral dose of MDL 28574A on
                          day 1 and are followed through day 7. In Part
                          B, patients receive single daily doses of the
                          drug on days 1 through 14 and are followed
                          through day 21.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940314)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Two positive tests for HIV
                          antibody (ELISA plus Western blot-identified
                          p24, gp41, or gp120/160). 2. CD4 count >= 500
                          cells/mm3. 3. No evidence of AIDS. 4. No
                          antiretroviral therapy within 30 days prior
                          to study entry. NOTE: Presence of
                          lymphadenopathy in two or more extrainguinal
                          sites, at least 1 cm in diameter for 3 or
                          more months, is permitted.
ELIGIBILITY               ASYM.
OTHER PROTOCOL NUMBERS    NDPR0002
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Drug Tolerance; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Maximum tolerated
                          dose (MTD), Pharmacokinetics, Drug dosing
                          schedule.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 7 - 14 days.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count >= 500
                          cells/mm3. 3. No evidence of AIDS. 4. No
                          antiretroviral therapy within 30 days prior
                          to study entry. NOTE: Presence of
                          lymphadenopathy in two or more extrainguinal
                          sites, at least 1 cm in diameter for 3 or
                          more months, is permitted. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 500 cells/mm3. ( 500
                          - 600 - 700 - 800 - plus ).
PATIENT AGE               AGE: 18 Years - 50 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or agree to
                          use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior participation in this trial. 2. Serious
                          physical or mental illness within 1 year
                          prior to study entry that would confound
                          interpretation of data. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 51 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: History of alcohol or drug
                          abuse within the past year.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          therapy within 30 days prior to study entry.
                          2. Known medications that alter renal,
                          hepatic, or hematologic/immunologic function
                          (such as barbiturates, phenothiazines,
                          cimetidine, and immunomodulators) within 14
                          days prior to study entry. 3. Routine
                          treatment with nonprescription medications
                          within 3 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Routine
                          treatment with nonprescription medications.
                          2. Treatment with other medications except
                          with approval of the investigator.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Clinically significant abnormalities on
                          routine hematology (other than CD4 count and
                          Western blot), serum chemistry, and
                          urinalysis. 2. Abnormal EKG. 3. Positive
                          stool guaiac. 4. Abnormal medical history or
                          physical exam including temperature, heart
                          rate, and blood pressure. 5. Clinically
                          significant organ abnormality or disease. 6.
                          Positive urine drug screen for illicit drugs.
                          7. Inability to comply with study procedures.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unavailable for inpatient stay
                          or for outpatient followup.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0202  MDL 28574
MANUFACTURERS             Drug 1: Marion Merrell Dow Inc 9300 Ward
                          Parkway Kansas City, MO 64114 Contact: David
                          Katterhenrich (816) 966-3482.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Part A: Single dose
                          administered on day 1. Part B: Daily doses
                          administered on days 1 through 14
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, solution
OTHER TREATMENT INFO.     TREATMENT DURATION: 1 to 14 days.
SUPPORTING AGENCY         Marion Merrell Dow Inc.
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Indolizines/ADMINISTRATION & DOSAGE/*ADVERSE
                          EFFECTS
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       121104-96-9 (MDL 28574)
LAST REVISION DATE        940314
ENTRY MONTH               9403
CALIFORNIA                Saint Francis Memorial Hospital 900 Hyde
                          Street San Francisco, CA 94109 Contact: Mark
                          Bowers (415) 353-6215 OPEN 940314.
 
104
UNIQUE IDENTIFIER         FDA/00598
PROTOCOL ID NUMBERS       FDA 220A
PROTOCOL TITLE            A Randomized, Open-Label Study of Alternative
                          Treatment Combinations of Dideoxycytidine
                          (HIVID; ddC) and Zidovudine (AZT) in Patients
                          With HIV Infection.
VERSION NUMBER & DATE     (940209)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To investigate the appropriate
                          dideoxycytidine (ddC) dose and zidovudine
                          (AZT) schedule for use in combination therapy
                          in patients with HIV infection. Methodology:
                          Patients are randomized to one of four
                          treatment arms. ddC is administered at either
                          0.375 or 0.75 mg every 8 hours. AZT is
                          administered at 100 mg every 4 hours while
                          awake (500 mg/day) or at 200 mg every 8 hours
                          (600 mg/day).
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to one
                          of four treatment arms. ddC is administered
                          at either 0.375 or 0.75 mg every 8 hours. AZT
                          is administered at 100 mg every 4 hours while
                          awake (500 mg/day) or at 200 mg every 8 hours
                          (600 mg/day).
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940209)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection. 2. CD4 count
                          100 - 500 cells/mm3.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    NV 14257
STUDY DESIGN              Randomized; Open Label; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Combination drug
                          therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 528 patients. (Half of
                          patients are AZT-naive and half are
                          AZT-experienced).
PROTOCOL DETAILS          STUDY DURATION: 12 months after enrollment of
                          last patient, up to 18 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 24 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count 100 -
                          500 cells/mm3. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 100 - 500 cells/mm3. (
                          100 - 200 - 300 - 400 - 500 ).
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0015  Dideoxycytidine
TRADE NAME OF SUBSTANCE   Drug 1 Retrovir
TRADE NAME OF SUBSTANCE   Drug 2 HIVID
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 mg q 4 h while
                          awake (500 mg/day) or 200 mg q 8 h (600
                          mg/day). Drug 2: 0.375 or 0.75 mg q 8 h
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 500 or 600 mg. Drug 2:
                          1.125 or 2.25 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, capsules. Drug
                          2: Oral, tablets
OTHER TREATMENT INFO.     END POINT: Immunologic and virologic
                          surrogate markers, survival, occurrence of
                          opportunistic infections and neoplasms,
                          adverse experiences, laboratory parameters.
SUPPORTING AGENCY         Hoffmann-La Roche, Incorporated, Burroughs
                          Wellcome.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zalcitabine/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        940209
ENTRY MONTH               9402
CALIFORNIA                Kaiser Permanente HIV Specialty Clinic 1505
                          North Edgemont Street Los Angeles, CA 90027
                          Contact: Karole Velzy (213) 667-5332 OPEN
                          940215.
CALIFORNIA                Kaiser Foundation Hospital 25825 South
                          Vermont Avenue Harbor City, CA 90710 Contact:
                          Larry Rick (310) 530-8420 OPEN 940215.
CALIFORNIA                Sharp Rees - Stealy Medical Group 2001 Fourth
                          Avenue San Diego, CA 92101 Contact: Peggy
                          Hammerdinger (619) 234-6261 X 302OPEN 940215.
CALIFORNIA                University of California San Francisco /
                          Department of Med 995 Potrero Avenue Ward 84
                          Building 80 San Francisco, CA 94110 Contact:
                          Diane Davies (415) 476-4082 X 846Contact:
                          Rowena Mah (415) 476-4082 X 840Contact: Kathy
                          Dybeck (415) 476-4082 X 840OPEN 940215.
COLORADO                  Denver Disease Control 605 Bannock Street
                          Denver, CO 80204 Contact: Ron Schimmel (303)
                          436-7282 Contact: Patrick Gourley (303)
                          436-7240 OPEN 940215.
DISTRICT OF COLUMBIA      Howard University Clinial Trials Unit 2112
                          Georgia Avenue NW Washington, DC 20060
                          Contact: Shella Taylor (202) 808-4786
                          Contact: Vikoria Trimmer (202) 808-4755 OPEN
                          940215.
DISTRICT OF COLUMBIA      Veterans Administration Medical Center 50
                          Irving Street N W Washington, DC 20422
                          Contact: Dr Fred Gordon (202) 745-8695
                          Contact: Patricia Ackerson (202) 745-8695
                          OPEN 940215.
FLORIDA                   Miami Veterans Administration Medical Center
                          1201 NW 16 Street Miami, FL 33125 Contact:
                          Alyce Bishop (305) 324-3929 OPEN 940215.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue 1st Floor Eliot Building
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 OPEN 940215.
GEORGIA                   Intergrated Care Center 3280 Howell Mill Road
                          Atlanta, GA 30327 Contact: Bill Emery (404)
                          355-6681 OPEN 940215.
ILLINOIS                  Rush Presbyterian St Luke's Medical Center
                          600 South Pauline Street Suite 143 Chicago,
                          IL 60612 Contact: Pam Urbanski (312) 942-5865
                          OPEN 940215.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 940215.
MASSACHUSETTS             New England Medical Center / Division of
                          Infectious Diseases 750 Washington Street Box
                          NEMCH 67 Boston, MA 02111 Contact: Christine
                          Sullivan (617) 956-7008 OPEN 940215.
MINNESOTA                 St Paul Ramsey Medical Center / HIV Program
                          Office 640 Jackson Street St Paul, MN 55101
                          Contact: Holly Melroe (612) 221-1280 OPEN
                          940215.
MISSOURI                  Washington University Clinical Trials Unit
                          4511 Forest Park Suite 304 St Louis, MO 63108
                          Contact: Michael Klebert (314) 454-0058 OPEN
                          940215.
NEW MEXICO                University of New Mexico School of Medicine
                          HSSB 302 Albuquerque, NM 87131 Contact:
                          Carolyn Williams (505) 277-5775 OPEN 940215.
NEW YORK                  St Luke's - Roosevelt Hospital Center HIV /
                          AIDS Clinical Antenucci Medical Research
                          Building 432 West 58th Street New York, NY
                          10019 Contact: Jim O'Connor (212) 523-6585
                          Contact: Juli Rivera (212) 523-6723 OPEN
                          940215.
NEW YORK                  Bronx Veteran's Affairs Medical Center 130
                          West Kingsbridge Road Bronx, NY 10466
                          Contact: Eileen Mclaughlin (718) 584-9000 X
                          586OPEN 940215.
NEW YORK                  SUNY at Brooklyn / Department of Medicine 450
                          Clarkson Avenue - Box 77 Brooklyn, NY 11203
                          Contact: Don Smith (718) 270-3370 Contact:
                          Adrian Marcel (718) 245-2800 OPEN 940215.
OHIO                      Ohio State University Hospital Clinic 456
                          West 10th Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judy Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 940215
                          ACTU: 2301.
OREGON                    Oregon Health Sciences University 3181 SW Sam
                          Jackson Park Road Portland, OR 97201 Contact:
                          Jan Weyeneth (503) 295-0850 OPEN 940215.
 
105
UNIQUE IDENTIFIER         FDA/00597
PROTOCOL ID NUMBERS       FDA 219A
PROTOCOL TITLE            A Phase I/II Study of the Safety and Efficacy
                          of Topical
                          1-(S)-(3-Hydroxy-2-phosphonylmethoxypropyl)cy-
                          tosine Dihydrate ( Cidofovir; HPMPC ) in the
                          Treatment of Condyloma Acuminatum in Patients
                          With HIV Infection.
VERSION NUMBER & DATE     (940204)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and tolerance
                          of topical cidofovir (HPMPC) therapy for
                          condyloma acuminatum in patients with HIV
                          infection. To investigate whether topical
                          HPMPC therapy can induce regression of
                          condyloma acuminatum in patients with HIV
                          infection. Methodology: Four groups of 10
                          patients each receive topical HPMPC at 0.3
                          percent concentration for 5 or 10 days total
                          or 1.0 percent concentration for 5 or 10 days
                          total, followed by 2 weeks of rest. When six
                          patients at a given dose and schedule have
                          completed treatment and follow-up without
                          significant toxicity, subsequent patients are
                          entered at the next higher dose level.
                          Patients are evaluated twice weekly during
                          treatment and once weekly during the rest
                          period. HPMPC may be extended for up to two
                          additional courses in patients who experience
                          no significant toxicity.
GENERAL DESCRIPTION       METHODOLOGY: Four groups of 10 patients each
                          receive topical HPMPC at 0.3 percent
                          concentration for 5 or 10 days total or 1.0
                          percent concentration for 5 or 10 days total,
                          followed by 2 weeks of rest. When six
                          patients at a given dose and schedule have
                          completed treatment and follow-up without
                          significant toxicity, subsequent patients are
                          entered at the next higher dose level.
                          Patients are evaluated twice weekly during
                          treatment and once weekly during the rest
                          period. HPMPC may be extended for up to two
                          additional courses in patients who experience
                          no significant toxicity.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940415)
DISEASE STUDIED           Condyloma acuminatum ( Venereal wart ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA and
                          Western blot. 2. Mean CD4 count >= 100
                          cells/mm3 on two serial measurements at least
                          1 week apart. 3. External anogenital
                          condyloma acuminatum confirmed by biopsy,
                          present for less than 1 year. NOTE: Warts on
                          anal, urethral, or vaginal mucosa will not be
                          studied.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    GS-93-302
STUDY DESIGN              Dose Escalating; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Drug dosing schedule.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 40 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 12 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. Mean CD4
                          count >= 100 cells/mm3. 3. External
                          anogenital condyloma acuminatum confirmed by
                          biopsy, present for less than 1 year. NOTE:
                          Warts on anal, urethral, or vaginal mucosa
                          will not be studied. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3. ( 100
                          - 200 - 300 - 400 - 500 - 600 - 700 - 800
                          plus ).
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: < 1+ proteinuria.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. AZT, ddI,
                          ddC, d4T, or 3TC. 2. Oral
                          trimethoprim/sulfamethoxazole. 3. Aerosolized
                          pentamidine. 4. Dapsone. 5. Fluconazole. 6.
                          Rifabutin. 7. Clarithromycin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of untreated syphilis or Bowenoid
                          papulosis. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: 1. Treatment for
                          anogenital warts. 2. Immunomodulators
                          (including interferons or systemic
                          corticosteroids). 3. Lymphocyte replacement
                          therapy. 4. Biologic response modifiers.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Podofilox
                          or any podophyllum resin preparation. 2.
                          Liquid nitrogen treatment. 3. Interferon
                          alpha. 4. Trichloracetic acid. 5. Other
                          treatments, topical or systemic, surgical or
                          ablative, known to have anti-papilloma
                          activity. 6. Other investigative drugs
                          (except d4T or 3TC) unless approved by the
                          sponsor.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active lesions of genital herpes, other skin
                          wounds, or active inflammatory skin disorders
                          in the same area as warts to be treated. 2.
                          Active medical problems sufficient to hinder
                          study compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0145  HPMPC
MANUFACTURERS             Drug 1: Gilead Sciences Inc 353 Lakeside
                          Drive Foster City, CA 94404 Contact: Dr John
                          Boggs (415) 573-4745.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Groups A and C: 0.3
                          and 1.0 percent, respectively, applied once
                          daily for 5 consecutive days, with possible
                          extensfor 2 additional courses. Groups B and
                          D: 0.3 and 1.0 percent, respectively, applied
                          oncefor 5 consecutive days per week for 2
                          weeks (10 days total), wipossible extension
                          for 2 additional courses
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 0.3 or 1.0 percent
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Topical
SUPPORTING AGENCY         Gilead Sciences Inc.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Condylomata Acuminata/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Cytosine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Opportunistic Infections/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Organophosphorus Compounds/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS/THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       113852-37-2
                          (1-(3-hydroxy-2-phosphonylmethoxypropyl)cytos-
                          ine)
LAST REVISION DATE        940415
ENTRY MONTH               9402
CALIFORNIA                Conant Medical Group C/O Clinical Research
                          1635 Divisadero Street / Suite 606 San
                          Francisco, CA 94115 Contact: Tanya Kocian
                          (415) 923-1333 Contact: (415) 661-2613
                          Contact: (415) 923-0222 OPEN 940215.
 
106
UNIQUE IDENTIFIER         FDA/00596
PROTOCOL ID NUMBERS       FDA 218A
PROTOCOL TITLE            A Phase I/II Study of the Safety and Efficacy
                          of Topical
                          1-(S)-(3-Hydroxy-2-phosphonylmethoxypropyl)cy-
                          tosine Dihydrate ( Cidofovir; HPMPC ) in the
                          Treatment of Refractory Mucocutaneous Herpes
                          Simplex Disease in Patients With AIDS.
VERSION NUMBER & DATE     (940223)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and tolerance
                          of topical cidofovir (HPMPC) therapy for
                          refractory mucocutaneous herpes simplex virus
                          disease in AIDS patients. To determine
                          whether topical HPMPC therapy can induce
                          re-epithelialization and healing of
                          refractory mucocutaneous herpes simplex virus
                          disease in AIDS patients. To evaluate the
                          virologic effects of topical HPMPC therapy on
                          herpes simplex virus shedding from refractory
                          lesions. Methodology: Patients are randomized
                          to receive topical therapy with placebo
                          (vehicle alone) or HPMPC at either 0.3 or 1.0
                          percent once daily for 5 days. Patients are
                          assessed to day 15; those with no significant
                          toxicity are eligible to receive open-label
                          topical HPMPC for up to 6 months.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive topical therapy with placebo (vehicle
                          alone) or HPMPC at either 0.3 or 1.0 percent
                          once daily for 5 days. Patients are assessed
                          to day 15; those with no significant toxicity
                          are eligible to receive open-label topical
                          HPMPC for up to 6 months.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940617)
DISEASE STUDIED           Herpes simplex, mucocutaneous.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA and
                          Western blot OR a diagnosis of AIDS by CDC
                          criteria. 2. Mucocutaneous herpes simplex
                          virus (HSV) infection confirmed by previous
                          viral culture and persisting without
                          improvement despite at least 10 days of
                          acyclovir at a minimum dose of 1 g/day (oral)
                          or 15 mg/kg/day (intravenous). 3. Lesions
                          that are accessible to serial measurement of
                          surface area or serial photography.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GS-93-301
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Multicenter; Drug Tolerance; 3-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 30 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 6 months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 9 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. Mucocutaneous
                          herpes simplex virus (HSV) infection
                          confirmed by previous viral culture and
                          persisting without improvement despite at
                          least 10 days of acyclovir at a minimum dose
                          of 1 g/day (oral) or 15 mg/kg/day
                          (intravenous). 3. Measurable lesions. 4.
                          Consent of parent or guardian if less than 18
                          years of age. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 6.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 20000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Proteinase < 2+ (10 g/l). Neutrophils
                          > 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: At least 10 days
                          of prior acyclovir at a minimum dose of 1
                          g/day (oral) or 15 mg/kg/day (intravenous).
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral therapy with AZT, ddI, ddC, or
                          d4T. 2. Oral trimethoprim/sulfamethoxazole.
                          3. Dapsone. 4. Atovaquone. 5. Fluconazole. 6.
                          Rifabutin. 7. Clarithromycin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 14 days
                          prior to study entry: 1. Immunomodulators
                          (such as corticosteroids or interferons). 2.
                          Lymphocyte replacement therapy. 3. Biologic
                          response modifiers. 4. Ganciclovir. 5.
                          Foscarnet. 6. Vidarabine. 7. Topical
                          trifluridine. 8. Other investigational drugs
                          with potential anti-HSV activity. 9.
                          Amphotericin. 10. Intravenous therapy for
                          PCP. Excluded within 4 weeks prior to study
                          entry: Chemotherapeutic agents.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Acyclovir. 2. Immunomodulators (such as
                          corticosteroids or interferons). 3.
                          Lymphocyte replacement therapy. 4. Biologic
                          response modifiers. 5. Ganciclovir. 6.
                          Foscarnet. 7. Vidarabine. 8. Topical
                          trifluridine. 9. Other investigational drugs
                          (except d4T). 10. Amphotericin. 11.
                          Intravenous therapy for PCP. 12.
                          Chemotherapeutic agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Active
                          medical problems sufficient to hinder study
                          compliance or assessment of treatment effect.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0145  HPMPC
MANUFACTURERS             Drug 1: Gilead Sciences Inc 353 Lakeside
                          Drive Foster City, CA 94404 Contact: Dr John
                          Boggs (415) 573-4745.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 0.3 or 1.0 percent
                          (or placebo) once daily for 5 days, then
                          possible extension for up to 6 months
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 0.3 or 1.0 percent
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Topical
OTHER TREATMENT INFO.     TREATMENT DURATION: Minimum of 5 days, with
                          possible extension of up to 6 months.
SUPPORTING AGENCY         Gilead Sciences Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Cytosine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Herpes Simplex/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Organophosphorus Compounds/ADMINISTRATION &
                          DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       113852-37-2
                          (1-(3-hydroxy-2-phosphonylmethoxypropyl)cytos-
                          ine)
LAST REVISION DATE        940617
ENTRY MONTH               9402
CALIFORNIA                University of Southern California / LAC - USC
                          Medical Center 1178 North Cummings Los
                          Angeles, CA 90033 Contact: Andrea Martelli
                          (213) 343-8280 OPEN 940617.
CALIFORNIA                San Francisco General Hospital 995 Potrero
                          Street San Francisco, CA 94110 Contact:
                          Rowena Mah (415) 476-9296 OPEN 940617.
CALIFORNIA                Mt Zion Medical Center / University
                          California San Francisco 1600 Divisadero
                          Street San Francisco, CA 94115 Contact: Dr
                          Jacob Lalezari (415) 476-6356 OPEN 940617.
ILLINOIS                  Rush Presbyterian - St Lukes Medical Ctr /
                          Sec of Infect Dis 1725 West Harrison Ave
                          Suite 143 Academic Facility Chicago, IL 60612
                          Contact: Donna Samano (312) 942-5865 OPEN
                          940617.
MARYLAND                  The Johns Hopkins Hospital 600 North Wolfe
                          Street / Wilmer 300 Baltimore, MD 21205
                          Contact: Linda Apuzzo (410) 614-1069 OPEN
                          940617.
NORTH CAROLINA            University of North Carolina Hospitals 547
                          Burnett - Womack Chapel Hill, NC 27599
                          Contact: Dr Sabina Lee (919) 966-6712 OPEN
                          940617.
OTHER                     University of British Columbia / University
                          Hospital 2211 Westbrook Mall Vancouver, BC
                          V6T 1Z3 Contact: April Bishop 604/822-7565
                          OPEN 940617.
 
107
UNIQUE IDENTIFIER         FDA/00595
PROTOCOL ID NUMBERS       FDA 217B
PROTOCOL TITLE            A Phase I/II Study of the Safety, Tolerance,
                          and Pharmacokinetics of Combination
                          Zidovudine (AZT) and
                          9-(2-Phosphonylmethoxyethyl)adenine (PMEA)
                          Treatment in HIV-Infected Patients.
VERSION NUMBER & DATE     (940204)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To study the safety, tolerance,
                          pharmacokinetics, and anti-HIV effects of
                          combination zidovudine (AZT) and PMEA
                          therapy. Methodology: Patients receive AZT
                          daily and intravenous PMEA three times weekly
                          for 4 weeks. An MTD will be defined for this
                          regimen.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive AZT daily and
                          intravenous PMEA three times weekly for 4
                          weeks. An MTD will be defined for this
                          regimen.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940415)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA and
                          Western blot. 2. Mean CD4 count <= 500
                          cells/mm3 on two measurements at least 1 day
                          apart. 3. Been receiving AZT at 500 mg daily
                          for at least 4 weeks prior to study entry.
                          NOTE: Kaposi's sarcoma is permitted provided
                          patient has not received any systemic therapy
                          for KS within the past 4 weeks. Patients with
                          a history of another malignancy must be
                          disease free for 6 months or more prior to
                          study entry.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    GS-93-204
STUDY DESIGN              Drug Combination; Drug Tolerance;
                          Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy, Pharmacokinetics, Combination
                          drug therapy, Maximum tolerated dose (MTD).
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. Mean CD4
                          count <= 500 cells/mm3. 3. Been receiving AZT
                          at 500 mg daily for at least 4 weeks prior to
                          study entry. 4. Life expectancy of at least 3
                          months. NOTE: Kaposi's sarcoma is permitted
                          provided patient has not received any
                          systemic therapy for KS within the past 4
                          weeks. Patients with a history of another
                          malignancy must be disease free for 6 months
                          or more prior to study entry. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 500 cells/mm3. ( 0 -
                          100 - 200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 750 cells/mm3.
                          <= 2+ proteinuria. Prothrombin time < 14 sec.
                          Partial thromboplastin < 35 sec.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT at a stable
                          dose for at least 4 weeks prior to study
                          entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Prophylactic
                          therapy with aerosolized pentamidine, oral
                          trimethoprim/sulfamethoxazole (Bactrim,
                          Septra) or dapsone, and fluconazole or
                          ketoconazole IF on a stable regimen for at
                          least 4 weeks prior to study entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Current use of illicit drugs
                          (e.g., heroin or cocaine). Ingestion of
                          substantial alcohol.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 weeks
                          prior to study entry: 1. ddI or ddC. 2.
                          Interferon alpha. 3. Ganciclovir. 4.
                          Foscarnet. 5. Diuretics. 6. Investigational
                          agents including d4T. 7. Chemotherapeutic
                          agents. 8. Amphotericin B. 9. Aminoglycoside
                          antibiotics. 10. Other nephrotoxic agents.
                          11. Immunomodulatory agents. Excluded within
                          4 weeks prior to study entry: Systemic
                          therapy for Kaposi's sarcoma.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. ddI or
                          ddC. 2. Interferon alpha. 3. Ganciclovir. 4.
                          Foscarnet. 5. Diuretics. 6. Investigational
                          agents including d4T. 7. Chemotherapeutic
                          agents. 8. Amphotericin B. 9. Aminoglycoside
                          antibiotics. 10. Other nephrotoxic agents.
                          11. Immunomodulatory agents. 12. Parenteral
                          therapy for an active, serious infection
                          (other than HIV infection).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Inadequate venous access. 2. Active, serious
                          infections (other than HIV infection)
                          requiring parenteral antibiotic therapy. 3.
                          Clinically significant cardiac disease,
                          including symptoms of ischemia, congestive
                          heart failure, or clinically significant
                          arrhythmia. 4. Active malignancy other than
                          Kaposi's sarcoma. 5. Mental incapacity or
                          illness that may affect compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0156  PMEA
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Gilead Sciences Inc 353 Lakeside
                          Drive Foster City, CA 94404 Contact: Dr Jay
                          Toole (415) 573-4751.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Three times weekly
                          for 4 weeks. Drug 2: 500 mg daily for 4 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 2: 500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV). Drug
                          2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 weeks.
SUPPORTING AGENCY         Gilead Sciences Inc.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adenine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/*ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS/PHARMACOKINETICS
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/*ADVERSE EFFECTS/PHARMACOKINETICS
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       106941-25-7
                          (9-(2-phosphonylmethoxyethyl)adenine)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940415
ENTRY MONTH               9402
MARYLAND                  National Cancer Institute 9000 Rockville Pike
                          Clinical Center Bethesda, MD 20892 Contact:
                          Sergio Bauza (301) 496-9054 OPEN / USA
                          accrual 940204.
 
108
UNIQUE IDENTIFIER         FDA/00594
PROTOCOL ID NUMBERS       FDA 217A
PROTOCOL TITLE            A Phase I/II Study of the Safety, Tolerance,
                          and Pharmacokinetics of
                          9-(2-Phosphonylmethoxyethyl)adenine (PMEA) in
                          Patients With Advanced HIV Disease.
VERSION NUMBER & DATE     (940204)
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To study the safety, tolerance,
                          pharmacokinetics, and anti-HIV effects of
                          PMEA when administered daily by intravenous
                          (IV) and/or subcutaneous (SC) injection in
                          patients with advanced HIV disease.
                          Methodology: Patients receive a single IV or
                          SC dose of PMEA daily for 4 weeks. A maximum
                          tolerated dose will be defined for these
                          regimens.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive a single IV or
                          SC dose of PMEA daily for 4 weeks. A maximum
                          tolerated dose will be defined for these
                          regimens.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940415)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA and
                          Western blot. 2. Elevated p24 antigen (> 40
                          pg/ml). 3. Mean CD4 count <= 100 cells/mm3 on
                          two measurements at least 1 week apart.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GS-92-202
STUDY DESIGN              Drug Tolerance; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug tolerance,
                          Drug efficacy, Pharmacokinetics, Maximum
                          tolerated dose (MTD).
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. Elevated p24
                          antigen (> 40 pg/ml). 3. Mean CD4 count <=
                          100 cells/mm3. 4. Life expectancy of at least
                          3 months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 100 cells/mm3. ( 0 -
                          100).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: <= 2+ proteinuria. Absolute
                          neutrophils >= 750 cells/mm3. Prothrombin
                          time < 14 sec. Partial thromboplastin time <
                          35 sec.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Other prior
                          antiretroviral therapy. 2. Prophylactic
                          therapy with aerosolized pentamidine, oral
                          trimethoprim/sulfamethoxazole (Bactrim,
                          Septra) or dapsone, and fluconazole or
                          ketoconazole.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Other
                          antiretroviral therapy IF on a stable dose
                          for at least 4 weeks prior to study entry. 2.
                          Prophylactic therapy with aerosolized
                          pentamidine, oral
                          trimethoprim/sulfamethoxazole (Bactrim,
                          Septra) or dapsone, and fluconazole or
                          ketoconazole IF on a stable prophylactic
                          regimen for at least 4 weeks prior to study
                          entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Substance abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 weeks
                          prior to study entry: 1. Investigational
                          agents other than stavudine (d4T). 2.
                          Interferon-alpha. 3. Ganciclovir. 4.
                          Foscarnet. 5. Diuretics. 6. Amphotericin B.
                          7. Aminoglycoside antibiotics. 8. Other
                          nephrotoxic agents. Excluded within 4 weeks
                          prior to study entry: Systemic therapy for
                          Kaposi's sarcoma.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Investigational agents other than stavudine
                          (d4T). 2. Interferon-alpha. 3. Ganciclovir.
                          4. Foscarnet. 5. Diuretics. 6. Amphotericin
                          B. 7. Aminoglycoside antibiotics. 8. Other
                          nephrotoxic agents. 9. Acyclovir at doses >=
                          2 g/day.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Inadequate venous access. 2. Active serious
                          infection (other than HIV infection)
                          requiring parenteral antibiotic therapy. 3.
                          Clinically significant cardiac disease,
                          including symptoms of ischemia, congestive
                          heart failure, or arrhythmia. 4. Psychiatric
                          disturbance or illness that may affect
                          compliance. 5. Malignancy other than Kaposi's
                          sarcoma.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0156  PMEA
MANUFACTURERS             Drug 1: Gilead Sciences Inc 353 Lakeside
                          Drive Foster City, CA 94404 Contact: Dr John
                          Boggs (415) 573-4745.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV) or
                          Subcutaneous (SC)
OTHER TREATMENT INFO.     TREATMENT DURATION: 4 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Requirement for
                          parenteral therapy for a serious illness
                          during the study.
SUPPORTING AGENCY         Gilead Sciences Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adenine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/*ADVERSE EFFECTS/PHARMACOKINETICS/
                          THERAPEUTIC USE
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS/PHARMACOKINETICS/THERAPEUTIC
                          USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       106941-25-7
                          (9-(2-phosphonylmethoxyethyl)adenine)
LAST REVISION DATE        940415
ENTRY MONTH               9402
 
109
UNIQUE IDENTIFIER         FDA/00684
PROTOCOL ID NUMBERS       FDA 216B
PROTOCOL TITLE            An Open-Label Study of the Safety and
                          Efficacy of Cidofovir ( HPMPC ) for the
                          Treatment of Relapsing Cytomegalovirus
                          Retinitis in Patients With AIDS.
VERSION NUMBER & DATE     (941011)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and tolerance
                          of cidofovir (HPMPC) infusions in AIDS
                          patients with relapsing cytomegalovirus (CMV)
                          retinitis. To determine the time to retinitis
                          progression in this patient population. To
                          evaluate the impact of cidofovir therapy on
                          visual acuity. Methodology: Patients are
                          randomized to receive intravenous HPMPC
                          either at 5 mg/kg/dose for both induction and
                          maintenance or at 5 mg/kg/dose for induction
                          and 3 mg/kg/dose for maintenance. Induction
                          consists of two consecutive weekly doses
                          followed by maintenance every other week. All
                          patients receive concomitant probenecid and
                          saline hydration. Treatment continues until
                          retinitis progression, as assessed by retinal
                          photographs, or treatment-limiting toxicity
                          occurs.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive intravenous HPMPC either at 5
                          mg/kg/dose for both induction and maintenance
                          or at 5 mg/kg/dose for induction and 3
                          mg/kg/dose for maintenance. Induction
                          consists of two consecutive weekly doses
                          followed by maintenance every other week. All
                          patients receive concomitant probenecid and
                          saline hydration. Treatment continues until
                          retinitis progression, as assessed by retinal
                          photographs, or treatment-limiting toxicity
                          occurs.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941028)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS by CDC criteria. 2. CMV
                          retinitis as assessed by presence of white,
                          fluffy, or granular retinal infiltrates with
                          or without hemorrhage. 3. Visual acuity in an
                          affected eye of three or more lines on the
                          ETDRS (Early Treatment Diabetic Retinopathy
                          Study) chart at 1 meter distance (Snellen
                          equivalent 8/200). 4. NO retinal detachment.
                          5. NO media opacity that precludes
                          visualization of the fundus of both eyes. 6.
                          If retinitis involves retinal zone 1, patient
                          must have had prior disease progression while
                          receiving at least 4 weeks of systemic
                          ganciclovir and 4 weeks of systemic
                          foscarnet, given as single drugs or in
                          combination, or while receiving at least 4
                          weeks of one drug with intolerance of the
                          other drug. If retinitis involves only zone 2
                          and/or zone 3, patient must have had prior
                          disease progresssion while receiving at least
                          4 weeks of systemic ganciclovir OR foscarnet.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GS-93-107
STUDY DESIGN              Open Label; Randomized; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until disease
                          progression or unacceptable toxicity occurs.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. CMV retinitis, with
                          severity as specified in the Disease Status
                          field. 3. Life expectancy of at least 3
                          months. 4. Consent of parent or guardian if
                          less than 18 years of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 55 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Proteinuria < 1+. Absolute neutrophils
                          >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral agents. 2. Oral
                          trimethoprim/sulfamethoxazole. 3. Aerosolized
                          pentamidine. 4. Dapsone. 5. Fluconazole. 6.
                          Rifabutin. 7. Filgrastim (G-CSF). 8.
                          Itraconazole. 9. HIV vaccines.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Drug or alcohol abuse that is
                          considered sufficient to hinder study
                          compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 2 days
                          prior to study entry: 1. Ganciclovir or
                          foscarnet. Excluded within one week prior to
                          study entry: 1. Amphotericin B. 2.
                          Aminoglycoside antibiotics. 3. Vidarabine. 4.
                          Intravenous pentamidine. 5. CMV hyperimmune
                          immunoglobulin. 6. Other nephrotoxic agents.
                          7. Other investigational agents with anti-CMV
                          activity. Excluded at any time: Prior
                          systemic or intravitreal HPMPC.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Amphotericin B. 2. Aminoglycoside
                          antibiotics. 3. Vidarabine. 4. Intravenous
                          pentamidine. 5. CMV hyperimmune
                          immunoglobulin. 6. Other nephrotoxic or
                          potentially nephrotoxic agents. 7. Other
                          investigational agents with anti-CMV
                          activity. 8. Ganciclovir. 9. Intravenous or
                          oral acyclovir (except following development
                          of herpetic lesion). 10. Foscarnet. 11.
                          Diuretics.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          clinically significant allergy to probenecid.
                          2. Clinically significant cardiac disease,
                          including symptoms of ischemia, congestive
                          heart failure, or arrhythmia. 3. Other active
                          medical problems sufficient to hinder study
                          compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0145  HPMPC
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0053  Probenecid
TRADE NAME OF SUBSTANCE   Drug 1 Cidofovir
MANUFACTURERS             Drug 1: Gilead Sciences Incorporated 353
                          Lakeside Drive Foster City, CA 94404 Contact:
                          Dr Robert Stagg (415) 572-6566.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 5 mg/kg weekly for 2
                          weeks (induction) followed by eith5 or 3
                          mg/kg q other week (maintenance)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV). Drug
                          2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Until disease progression
                          or unacceptable toxicity occurs.
OTHER TREATMENT INFO.     END POINT: Safety, time to retinitis
                          progression or death, changes in visual
                          acuity.
SUPPORTING AGENCY         Gilead Sciences Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Cytosine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Organophosphorus Compounds/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Probenecid/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       113852-37-2
                          (1-(3-hydroxy-2-phosphonylmethoxypropyl)cytos-
                          ine)
CAS REGISTRY NUMBER       57-66-9 (Probenecid)
LAST REVISION DATE        941028
ENTRY MONTH               9411
NEW JERSEY                Besselaar Associates 103 College Road East
                          Princeton, NJ 08540-6681 Contact: Alan Boylan
                          (609) 452-8550 OPEN / USA accrual 941028.
 
110
UNIQUE IDENTIFIER         FDA/00593
PROTOCOL ID NUMBERS       FDA 216A
PROTOCOL TITLE            A Phase II/III Study of the Safety and
                          Efficacy of
                          1-(S)-(3-Hydroxy-2-phosphonylmethoxypropyl)cy-
                          tosine Dihydrate ( Cidofovir; HPMPC ) for the
                          Treatment of Peripheral Cytomegalovirus
                          Retinitis in Patients With AIDS.
VERSION NUMBER & DATE     (940503)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To determine whether cidofovir
                          (HPMPC) therapy administered by intravenous
                          infusion can extend the time to progression
                          of peripheral cytomegalovirus (CMV) retinitis
                          in AIDS patients. To evaluate the safety and
                          tolerance of HPMPC therapy when administered
                          by intravenous infusion in AIDS patients with
                          CMV retinitis that is not immediately
                          sight-threatening. To evaluate the virologic
                          effects of intravenous HPMPC therapy on CMV
                          shedding in urine, blood, and/or semen. To
                          evaluate the impact of HPMPC therapy on
                          visual acuity. Methodology: Patients are
                          randomized to one of two treatment arms.
                          Group A receives HPMPC by IV infusion weekly
                          for 2 consecutive weeks (induction) and then
                          every other week (maintenance) with oral
                          probenecid and IV hydration. Group B receives
                          no treatment until the time of retinitis
                          progression (deferred treatment), at which
                          time they receive the same regimen as Group
                          A, provided retinitis progression is not
                          immediately sight-threatening.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to one
                          of two treatment arms. Group A receives HPMPC
                          by IV infusion weekly for 2 consecutive weeks
                          (induction) and then every other week
                          (maintenance) with oral probenecid and IV
                          hydration. Group B receives no treatment
                          until the time of retinitis progression
                          (deferred treatment), at which time they
                          receive the same regimen as Group A, provided
                          retinitis progression is not immediately
                          sight-threatening.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940415)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Diagnosis of AIDS by CDC
                          criteria. 2. Diagnosis of peripheral (not
                          immediately sight-threatening) CMV retinitis.
                          Lesions must be at least 1500 micrometers
                          from the margin of the optic disc and 3000
                          micrometers from the center of the fovea. One
                          lesion must be at least one-quarter disc area
                          such that it can be photographed. 3. Visual
                          acuity in the affected eye of >= three lines
                          on the ETDRS (Early Treatment Diabetic
                          Retinopathy Study) chart at 1 m distance.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GS-93-106
STUDY DESIGN              Randomized; Controlled; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 48 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Diagnosis of AIDS by CDC criteria.
                          2. Diagnosis of peripheral (not immediately
                          sight-threatening) CMV retinitis. 3. Visual
                          acuity in the affected eye of >= three lines
                          on the ETDRS (Early Treatment Diabetic
                          Retinopathy Study) chart at 1 m distance. 4.
                          Life expectancy of at least 3 months. 5.
                          Consent of parent or guardian in patients
                          less than 18 years of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 55 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: < 1+ proteinuria. Absolute neutrophils
                          >= 750 cells/mm3.
PATIENT AGE               AGE: 13 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Acyclovir. 2.
                          Prior ganciclovir, foscarnet, or CMV
                          hyperimmune immunoglobulin if given solely as
                          prophylaxis.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Antiretroviral agents. 2. Oral
                          trimethoprim/sulfamethoxazole. 3. Aerosolized
                          pentamidine. 4. Dapsone. 5. Fluconazole. 6.
                          Rifabutin. 7. Filgrastim (G-CSF). 8. p24
                          vaccine.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Not breast-feeding. No
                          abstinence or no agreement to use effective
                          method of birth control / contraception
                          during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Drug or alcohol abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Prior
                          ganciclovir, foscarnet, or CMV hyperimmune
                          immunoglobulin as therapy for CMV disease
                          (although permitted if previously received
                          solely as prophylaxis). Excluded within 1
                          week prior to study entry: 1. Amphotericin B.
                          2. Vidarabine. 3. Other nephrotoxic agents.
                          4. Aminoglycoside antibiotics. 5. Intravenous
                          pentamidine.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Acyclovir
                          (may be reinstituted following development of
                          herpetic lesions). 2. Ganciclovir. 3.
                          Foscarnet. 4. Amphotericin B. 5. Diuretics.
                          6. Aminoglycoside antibiotics. 7. CMV
                          hyperimmune immunoglobulin. 8. Intravenous
                          pentamidine. 9. Other nephrotoxic agents. 10.
                          Other investigational drugs with potential
                          nephrotoxicity.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Media
                          opacity that precludes visualization of the
                          fundus of both eyes. 2. Retinal detachment.
                          3. Clinically significant cardiac disease,
                          including symptoms of ischemia, congestive
                          heart failure, or arrhythmia. 4. Active
                          medical problems considered sufficient to
                          hinder study compliance. 5. Known clinically
                          significant allergy to probenecid.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0145  HPMPC
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0053  Probenecid
MANUFACTURERS             Drug 1: Gilead Sciences Incorporated 353
                          Lakeside Drive Foster City, CA 94404 Contact:
                          Dr Robert Stagg (415) 572-6566.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 5 mg/kg weekly for 2
                          consecutive weeks, followed by 5 mg/kg q
                          other week
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV). Drug
                          2: Oral
SUPPORTING AGENCY         Gilead Sciences Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Antiviral Agents/ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Cytosine/ANALOGS & DERIVATIVES/ADMINISTRATION
                          & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Organophosphorus Compounds/ADMINISTRATION &
                          DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Probenecid/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       113852-37-2
                          (1-(3-hydroxy-2-phosphonylmethoxypropyl)cytos-
                          ine)
CAS REGISTRY NUMBER       57-66-9 (Probenecid)
LAST REVISION DATE        940415
ENTRY MONTH               9402
CALIFORNIA                University of Southern California / LAC - USC
                          Medical Center 1175 North Cummings Street Los
                          Angeles, CA 90033 Contact: Dr Francoise
                          Kramer (213) 343-8316 OPEN 940215.
CALIFORNIA                University of California / Irvine Medical
                          Center 101 The City Drive Orange, CA 92668
                          Contact: Dr Baruch Kuppermann (714) 856-6256
                          OPEN 940215.
CALIFORNIA                Mt Zion Medical Center 1600 Divisadero Street
                          San Francisco, CA 94115 Contact: Eileen
                          Glutzer (415) 476-6356 OPEN 940215.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02215 Contact: Dr David Ives (617)
                          735-3661 OPEN 940215.
NORTH CAROLINA            University of North Carolina Hospitals 547
                          Burnett - Womack Chapel Hill, NC 27599
                          Contact: Dr Joseph Eron (919) 966-2537 OPEN
                          940215.
NEW YORK                  University of Rochester Medical Center 30
                          North Union Street Rochester, NY 14607
                          Contact: Kathy Champagne (716) 232-2560 OPEN
                          940215.
OTHER                     Chelsea & Westminster Hospital / St Stephen's
                          Clinic 369 Fulham Road London, UK SW10 9NH
                          Contact: Dr Michael Youle 011-44-81-746-5594
                          OPEN 940215.
 
111
UNIQUE IDENTIFIER         FDA/00611
PROTOCOL ID NUMBERS       FDA 214A
PROTOCOL TITLE            A Randomized Open-Label Study of the
                          Tolerability and Efficacy of Clarithromycin
                          and Ethambutol in Combination With or Without
                          Clofazimine for the Treatment of Disseminated
                          MAC (dMAC) in Patients With AIDS.
VERSION NUMBER & DATE     (940414)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To assess the tolerability
                          of the combination regimen of clarithromycin
                          plus ethambutol with or without clofazimine
                          in patients with disseminated Mycobacterium
                          avium Complex (dMAC). SECONDARY: To determine
                          the proportion of patients achieving a
                          sterile blood culture along with the time
                          required to achieve it. To determine the
                          duration of bacteriological response, defined
                          as length of time that blood cultures remain
                          sterile.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (931222)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. History of HIV seropositivity.
                          2. Clinical signs and symptoms consistent
                          with disseminated MAC (e.g., diarrhea,
                          periodic fevers, night sweats, weight loss,
                          hepatomegaly, and/or splenomegaly). 3.
                          Positive blood culture for MAC within 4 weeks
                          prior to study entry. NOTE: Patients with
                          active opportunistic infections other than
                          dMAC are permitted if dosage and clinical
                          parameters have been stable for 4 weeks prior
                          to enrollment.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    M93-069
STUDY DESIGN              Randomized; Open Label; Drug Tolerance; Drug
                          Combination; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug tolerance, Drug efficacy,
                          Combination drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. History of HIV seropositivity. 2.
                          Disseminated MAC. 3. Positive blood culture
                          for MAC within 4 weeks prior to study entry.
                          4. Consent of parent or guardian if less than
                          18 years of age. 5. Ability to complete the
                          study. NOTE: Patients with active
                          opportunistic infections other than dMAC are
                          permitted if dosage and clinical parameters
                          have been stable for 4 weeks prior to
                          enrollment. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 10 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: <= 40.
PATIENT INCLUSION CRIT.   OTHER: Total neutrophils >= 600 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of allergy or hypersensitivity to
                          macrolides, ethambutol, or clofazimine.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Other
                          antimycobacterials, including
                          aminoglycosides, ansamycin (rifabutin), other
                          macrolides (such as clindamycin), quinolones,
                          and rifampin, between screening and study
                          entry. 2. Clarithromycin or azithromycin as
                          prophylaxis or treatment (for any cause) for
                          more than 14 days cumulative within the past
                          2 months.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Active
                          therapy with carbamazepine or theophylline,
                          unless investigator agrees to carefully
                          monitor blood levels. 2. Active therapy with
                          investigational drugs other than treatment
                          for HIV disease, except with approval of the
                          sponsor. 3. Concomitant terfenadine (Seldane
                          or Seldane-D) or astemizole (Hismanal). 4.
                          Amikacin. 5. Azithromycin. 6. Capreomycin. 7.
                          Ciprofloxacin. 8. Cycloserine. 9.
                          Ethionamide. 10. Gentamicin. 11. Kanamycin.
                          12. Levofloxacin. 13. Lomefloxacin. 14.
                          Ofloxacin. 15. Rifampin. 16. Rifabutin. 17.
                          Sparfloxacin. 18. Streptomycin. 19. Any other
                          aminoglycosides, quinolones, and macrolides.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0099  Clarithromycin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0111  Ethambutol
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0067  Clofazimine
TRADE NAME OF SUBSTANCE   Drug 1 Biaxin
MANUFACTURERS             Drug 1: Abbott Laboratories One Abbott Park
                          Road / Department 422 Abbott Park, IL
                          60064-3500 Contact: Medical Services (708)
                          938-0601.
MANUFACTURERS             Drug 2: Lederle Laboratories Professional
                          Services Department Pearl River, NY 10965
                          Contact: Professional Services (914)
                          735-2815.
MANUFACTURERS             Drug 3: Ciba Pharmaceutical Company 556
                          Morris Avenue Summit, NJ 07901 Contact:
                          Medical Services Department (908) 277-5000.
SUPPORTING AGENCY         Abbott Laboratories.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Clarithromycin/*ADVERSE EFFECTS/THERAPEUTIC
                          USE
MESH HEADING              Clofazimine/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       2030-63-9 (Clofazimine)
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       81103-11-9 (Clarithromycin)
LAST REVISION DATE        931222
ENTRY MONTH               9403
CALIFORNIA                Kaiser Permanente Medical Center 1505 North
                          Edgemont Street Los Angeles, CA 90027
                          Contact: Dr Joel Ruskin (213) 667-3715 OPEN
                          931222.
CALIFORNIA                Kaiser Permanente Medical Center / HIV
                          Research Unit 2590 Geary Blvd San Francisco,
                          CA 94115 Contact: Gretchen Van Raalte (415)
                          202-3482 Contact: Barbara LeMaire (415)
                          202-3480 Contact: Dr Jeffrey Fessel (415)
                          202-3486 OPEN 931222.
CALIFORNIA                Santa Clara Valley Medical Center / AIDS
                          Program 751 South Bascom Avenue San Jose, CA
                          95128-2699 Contact: Carol Kane (408) 885-4316
                          Contact: Dr Carol Kemper (assoc dir) (408)
                          885-4300 OPEN 931222.
CALIFORNIA                University of California Davis / Medical
                          Center 2221 Stockton Boulevard PCC Room 3107
                          Sacramento, CA 95817 Contact: Sheila Enders
                          (916) 734-7004 OPEN 931222.
DISTRICT OF COLUMBIA      George Washington University / Hemophilia
                          Treatment Center 2150 Pennsylvania Avenue N W
                          Washington, DC 20037 Contact: Charlotte
                          Quinlan (202) 994-3076 OPEN 931222.
FLORIDA                   Dr Margaret Fischel Elliott Building / 1st
                          Floor / 1800 Northwest 10th Avenue Miami, FL
                          33136 Contact: Dr Margaret Fischel (305)
                          547-3848 OPEN 931222.
FLORIDA                   Dr Bienvenido Yangco Suite 14 Tampa, FL 33614
                          Contact: Vicky Kenyon (813) 870-4760 OPEN
                          931222.
ILLINOIS                  Rush Presbyterian St Luke's Medical Center
                          600 South Pauline Street Suite 143 Chicago,
                          IL 60612 Contact: Pam Urbanski (312) 942-5865
                          OPEN 931222.
LOUISIANA                 Tulane University Medical School / AIDS
                          Clinical Trials Unit 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Russell
                          Strada (504) 584-3605 OPEN 931222.
MARYLAND                  Johns Hopkins University / School of Medicine
                          1830 East Monument Street / Suite 7400
                          Baltimore, MD 21205 Contact: Sara Lynn Elkin
                          (410) 955-1754 OPEN 931222.
NORTH CAROLINA            University of North Carolina at Chapel Hill /
                          UNC CTU 516 Burnett Womack / CB# 7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-7883 OPEN 931222.
NEW YORK                  Beth Israel Medical Center First Avenue at
                          16th Street / Div Inf Dis / DAZIAN New York,
                          NY 10003 Contact: Ann Marshak (212) 420-4432
                          OPEN 931222.
NEW YORK                  Mount Sinai Hospital / Clinical Trials Unit
                          One Gustave L Levy Place / Box 1042 New York,
                          NY 10029-6574 Contact: Dr Eileen Chusid (212)
                          241-8254 OPEN 931222.
OTHER                     Dr Javier Morales 1451 Ashford Avenue / 2nd
                          Floor / Suite H Condado San Juan, PR 00907
                          Contact: Carmen DeJesus (809) 722-0455 OPEN
                          931222.
PENNSYLVANIA              Dr Stephen Hauptman 1015 Chestnut Street /
                          Suite 610 Philadelphia, PA 19107 Contact:
                          Lyle Jew (215) 955-7785 OPEN 931222.
 
112
UNIQUE IDENTIFIER         FDA/00588
PROTOCOL ID NUMBERS       FDA 213A
PROTOCOL TITLE            A Pilot Study of Fluconazole Plus Flucytosine
                          for the Treatment of AIDS Patients With Acute
                          Cryptococcal Meningitis.
VERSION NUMBER & DATE     (940104)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate and estimate the safety
                          and efficacy of the combination of
                          fluconazole and flucytosine as treatment for
                          acute cryptococcal meningitis in patients
                          with AIDS.
GENERAL DESCRIPTION       RATIONALE: Fluconazole and flucytosine have
                          different mechanisms of action. Since
                          fluconazole has not been associated with
                          hematologic suppression and does not produce
                          renal impairment that can result in higher
                          serum flucytosine levels, this combination
                          may be better tolerated than is amphotericin
                          B plus flucytosine.
GENERAL DESCRIPTION       METHODOLOGY: Patients in each cohort receive
                          a lower dose of fluconazole alone or in
                          combination with flucytosine, or a higher
                          dose of fluconazole alone. Doses in
                          subsequent cohorts are escalated if safety
                          data in the previous cohort is satisfactory.
                          Patients are evaluated weekly for the first 4
                          weeks and every 2 weeks thereafter. Therapy
                          continues until 8 weeks after the CSF becomes
                          culture negative, up to a maximum of 26
                          weeks.
PROTOCOL PHASE            Pilot Study
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940413)
DISEASE STUDIED           Cryptococcal meningitis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS by CDC criteria. 2. One
                          of the following: o Identification of
                          Cryptococcal neoformans in culture or lumbar
                          CSF. o Clinical and CSF findings compatible
                          with crytococcal meningitis plus a) positive
                          CSF India ink exam; OR b) culture or biopsy
                          evidence of extraneural cryptococcal
                          infection; OR c) positive serum or CSF
                          cryptococcal antigen test; OR d) biopsy
                          evidence of CNS cryptococcal infection. 3. No
                          evidence of acute or chronic meningitis of
                          any etiology other than cryptococcosis.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    R-0202
STUDY DESIGN              Drug Tolerance; Randomized
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Combination and single drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 64 patients. (24 patients
                          in cohorts one and two and 16 patients in
                          cohort three)
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. Evidence of Cryptococcal
                          neoformans in culture or lumbar CSF OR
                          clinical and CSF findings compatible with
                          crytococcal meningitis. 3. No evidence of
                          acute or chronic meningitis of any etiology
                          other than cryptococcosis. 4. Life expectancy
                          of at least 2 weeks. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1250 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 40 ml/min.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 3 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Allowed: Prior radiation
                          therapy for mucocutaneous Kaposi's sarcoma.
OTHER PATIENT INCL. CH.   CONCURRENT TREATMENT: Allowed: Radiation
                          therapy for mucocutaneous Kaposi's sarcoma.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Prior antiviral
                          therapy (AZT, DHPG). 2. Prophylaxis for
                          Pneumocystis carinii pneumonia.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Antiviral
                          therapy (AZT, DHPG). 2. Prophylaxis for
                          Pneumocystis carinii pneumonia. 3. Treatment
                          for intercurrent opportunistic infection.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of allergy to or intolerance of
                          imidazoles, azoles, or flucytosine. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than 1
                          mg/kg amphotericin B. 2. Systemic antifungal
                          agents within 7 days prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Concomitant
                          use of any antifungal agent other than study
                          drug.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Relapsing on maintenance triazole therapy for
                          cryptococcal meningitis. 2. Unable to take
                          oral medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0005  Fluconazole
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0049  Flucytosine
TRADE NAME OF SUBSTANCE   Drug 1 Diflucan
MANUFACTURERS             Drug 1: Pfizer Incorporated / Roerig Division
                          235 East 42nd Street New York, NY 10017-7851
                          Contact: Professional Information (212)
                          573-2187.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: First cohort: 800 or
                          1200 mg daily until 8 weeks after the CSF
                          becomes culture negative, up to a maximum of
                          26 weeks. Second cohort; 1200 or 1600 mg
                          daily until 8 weeks after the CSbecomes
                          culture negative, up to a maximum of 26
                          weeks. Third cohort: 1600 mg daily until 8
                          weeks after the CSF becomesculture negative,
                          up to a maximum of 26 weeks. Drug 2: 150
                          mg/kg daily for 4 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 800 - 1600 mg. Drug 2:
                          150 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: Maximum of 26 weeks.
SUPPORTING AGENCY         Pfizer Incorporated / Roerig Division.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cryptococcosis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Fluconazole/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Flucytosine/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Meningitis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       2022-85-7 (Flucytosine)
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        940413
ENTRY MONTH               9401
CALIFORNIA                Los Angeles County USC Medical Center / Dr.
                          Robert Larson 1129 North State Street Los
                          Angeles, CA 90033 Contact: DeAnn Diamond
                          (213) 226-3580 OPEN 940107.
CALIFORNIA                University of California / UCSD Treatment
                          Center 2760 Fifth Avenue / Suite 300 San
                          Diego, CA 92103-6325 Contact: Chris Fegan
                          (619) 543-8080 Contact: Ben Freeman (619)
                          543-8080 OPEN 940107.
CALIFORNIA                UCI Medical Center / Division of Infectious
                          Diseases 101 City Drive South / Building 53
                          Route 81 Orange, CA 92668 Contact: Marlene
                          Fugate (714) 456-7612 Contact: Sheila
                          Fitzgibbons (714) 456-7747 OPEN 940107.
 
113
UNIQUE IDENTIFIER         FDA/00585
PROTOCOL ID NUMBERS       FDA 212A
PROTOCOL TITLE            A Dose-Escalating Study of Ro 31-8959 (HIV
                          Protease Inhibitor) in Patients With HIV
                          Disease.
VERSION NUMBER & DATE     (940104)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To investigate the toxicity,
                          antiviral activity, and pharmacokinetics in
                          HIV-infected patients receiving 16 weeks of
                          oral Ro 31-8959 at one of two doses.
                          Methodology: Cohorts of 16 patients receive
                          either 600 or 1200 mg Ro 31-8959 six times
                          per day for 20 weeks. Administration of the
                          higher dose will proceed only after 2-week
                          safety data for the first eight patients on
                          the lower dose has been reviewed.
GENERAL DESCRIPTION       METHODOLOGY: Cohorts of 16 patients receive
                          either 600 or 1200 mg Ro 31-8959 six times
                          per day for 20 weeks. Administration of the
                          higher dose will proceed only after 2-week
                          safety data for the first eight patients on
                          the lower dose has been reviewed.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940101)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA confirmed by Western blot. 2. CD4 count
                          200 - 500 cells/mm3. 3. No evidence of viral
                          mutation at codon 48, 74, 90, or 215. 4. HIV
                          RNA quantifiable by PCR. NOTE: Fifty percent
                          of patients must have measurable p24 antigen
                          levels (> 31 pg/ml).
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    EV 14757
STUDY DESIGN              Open Label; Drug Tolerance; Dose Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Pharmacokinetics.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 32 patients. (16 patients
                          per treatment arm)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 20 weeks.
PROTOCOL DETAILS          STUDY DURATION: 1 year.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count 200 - 500 cells/mm3. 3. No evidence of
                          viral resistance. 4. HIV RNA quantifiable by
                          PCR. 5. Negativity for HBsAg, HBeAg, and
                          anti-HBc. NOTE: Fifty percent of patients
                          must have measurable p24 antigen levels (> 31
                          pg/ml). [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.0 g/dl. (Must not be
                          transfusion dependent).
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 1.25 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 1.25 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils 750 cells/mm3.
                          Total serum amylase < 2 x ULN (unless
                          fractionation reveals that elevated fraction
                          is salivary amylase OR patient has
                          macroamylasemia OR has a normal lipase
                          value).
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR TREATMENT: Allowed: Transfusion,
                          provided patient has not received more than
                          three units of blood within a 21-day period.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Unexplained temperature >= 38.5 C (101.5 F)
                          persisting for 14 days or more within a
                          30-day period. 2. Unexplained, chronic
                          diarrhea persisting for 14 days or more
                          within a 30-day period. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy other than local skin radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          treatment with an HIV proteinase inhibitor.
                          2. AZT within 30 days prior to study entry OR
                          lasting more than 1 year. 3. Other
                          antiretroviral therapy (besides AZT) within
                          30 days prior to study entry OR lasting more
                          than 14 days. 4. Acute therapy for an
                          opportunistic infection within 14 days prior
                          to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antineoplastic agents. 2. Concomitant or
                          maintenance treatment with excluded
                          experimental drugs and drugs with known
                          nephrotoxic or hepatotoxic potential.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Active opportunistic infection requiring
                          immediate treatment, such as tuberculosis,
                          cytomegalovirus, cerebral toxoplasmosis, and
                          Pneumocystis carinii pneumonia. 2. Unable to
                          maintain adequate oral intake. 3. Clinically
                          significant vomiting and/or diarrhea. 4.
                          Malignancy, visceral Kaposi's sarcoma, or
                          lymphoma that will require systemic
                          chemotherapy within the next 12 months. 5.
                          Unable to comply with protocol requirements,
                          in the judgment of the investigator. 6. Any
                          grade 3 or worse laboratory or clinical
                          abnormality.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0164  Ro 31-8959
MANUFACTURERS             Drug 1: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 600 or 1200 mg six
                          times per day for 20 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 3600 or 7200 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 20 weeks.
SUPPORTING AGENCY         Stanford University Medical Center.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Isoquinolines/*ADVERSE EFFECTS/
                          PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Quinolines/*ADVERSE EFFECTS/PHARMACOKINETICS/
                          THERAPEUTIC USE
CAS REGISTRY NUMBER       127779-20-8 (Ro 31-8959)
LAST REVISION DATE        940101
ENTRY MONTH               9401
CALIFORNIA                Stanford University Medical Center SUMC S-156
                          Stanford, CA 94305 Contact: Jane Norris (415)
                          723-2805 Contact: (415) 723-6231 OPEN 940101.
 
114
UNIQUE IDENTIFIER         FDA/00583
PROTOCOL ID NUMBERS       FDA 211A
PROTOCOL TITLE            A Phase II/III Study of Cysteamine
                          (Mercaptoethylamine) and Zidovudine for the
                          Treatment of HIV Disease.
VERSION NUMBER & DATE     (931215)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To determine the safety and
                          tolerance of low-dose versus high-dose
                          cysteamine administered concurrently with
                          zidovudine (AZT). To determine the
                          pharmacokinetics and effects on immune
                          function and viral load in patients receiving
                          these drug regimens. Methodology: Patients
                          receive high or low doses of cysteamine plus
                          AZT or placebo plus AZT. The target dose of
                          cysteamine is determined by titration of the
                          dose over a 6-week period, after which the
                          patient receives 24 additional weeks of
                          treatment. An initial cohort of 36 patients
                          will be enrolled in a 10-week pilot phase.
                          Accrual will be temporarily suspended while
                          data from the pilot phase is assessed.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive high or low
                          doses of cysteamine plus AZT or placebo plus
                          AZT. The target dose of cysteamine is
                          determined by titration of the dose over a
                          6-week period, after which the patient
                          receives 24 additional weeks of treatment. An
                          initial cohort of 36 patients will be
                          enrolled in a 10-week pilot phase. Accrual
                          will be temporarily suspended while data from
                          the pilot phase is assessed.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940503)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA confirmed by Western blot. 2. CD4 count
                          300 - 500 cells/mm3. 3. Prior AZT therapy for
                          at least 3 months but less than 12 months
                          prior to study entry. 4. No past or current
                          AIDS-defining opportunistic infection by CDC
                          definition.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    CYST-9304
STUDY DESIGN              Randomized; Double-Blind; 3-Arm; Dose
                          Comparison; Drug Tolerance; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Pharmacokinetics, Combination and single drug
                          therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 300 patients. (100
                          patients in each of three treatment arms)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 31
                          weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count 300 - 500 cells/mm3. 3. Prior AZT
                          therapy for at least 3 months but less than
                          12 months prior to study entry. 4. No past or
                          current AIDS-defining opportunistic
                          infection. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9.5 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 300 - 500 cells/mm3. (
                          300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 1000 cells/mm3.
                          Alkaline phosphatase < 3 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT for at least
                          3 months but no more than 12 months prior to
                          study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Chemoprophylaxis for Pneumocystis carinii
                          pneumonia, candidiasis, Mycobacterium
                          tuberculosis, and herpes as prescribed by the
                          investigator. 2. Recombinant erythropoietin
                          and G-CSF if clinically indicated.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of treatment-limiting intolerance to
                          500-600 mg AZT daily as manifested by the
                          same recurrent grade 3 toxicity or any prior
                          grade 4 toxicity. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiation
                          therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Prior
                          antiretroviral therapy other than AZT.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral therapy other than AZT. 2.
                          Immunosuppressive drugs. 3. Investigational
                          HIV drugs/therapies other than study drug. 4.
                          Interferon. 5. Steroids. 6. Hematopoietins.
                          7. Cytotoxic chemotherapy including
                          Adriamycin, bleomycin, and vincristine.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Kaposi's sarcoma requiring systemic therapy.
                          2. Active malignancy other than basal cell
                          carcinoma or in situ cervical carcinoma.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0003  Cysteamine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Mylan Laboratories Inc 1030 Century
                          Building Pittsburgh, PA 15222 Contact:
                          Kristine Hartman (800) 858-8490 Contact:
                          (412) 232-0100.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 2: 200 mg thrice daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 2: 600 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, capsules. Drug
                          2: Oral
SUPPORTING AGENCY         Mylan Laboratories Inc.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cysteamine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Zidovudine/ADVERSE EFFECTS/PHARMACOKINETICS/
                          *THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       60-23-1 (Cysteamine)
LAST REVISION DATE        940503
ENTRY MONTH               9312
FLORIDA                   Saint Josephs Hospital / Infectious Disease
                          Research Unit 4600 N Habana Suite 14 Tampa,
                          FL 33614 Contact: Vicki Kenyon (813) 870-4760
                          Contact: (Tampa Gen Hospital) (813) 870-4759
                          OPEN 931215.
LOUISIANA                 Tulane University Medical School / AIDS
                          Clinical Trials Unit 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Russell
                          Strada (504) 584-3605 OPEN 931215.
NORTH CAROLINA            Bowman Gray School of Medicine / North
                          Carolina Baptist Hosp Medical Center
                          Boulevard Winston-Salem, NC 27157-1042
                          Contact: Mary Green (910) 716-4584 OPEN
                          931215.
NEW YORK                  SUNY at Stony Brook Health Sciences Center /
                          Div Infect Dis HSC T 15 Room 080 Stony Brook,
                          NY 11794-8153 Contact: Ruth Ann Burk (516)
                          444-1658 OPEN 931215.
RHODE ISLAND              Independent Research Nurses Inc 769 Park
                          Avenue Cranston, RI 02910 Contact: Dr Dennis
                          Mikolich (401) 467-7760 OPEN 940503.
 
115
UNIQUE IDENTIFIER         FDA/00574
PROTOCOL ID NUMBERS       FDA 210A
PROTOCOL TITLE            Randomized, Double-Blind, Placebo-Controlled
                          Comparative Dose-Response Study of Two Doses
                          of Atevirdine Mesylate (U-87201E) in
                          Combination With Fixed Doses of Zidovudine
                          (AZT) in HIV+ Patients.
VERSION NUMBER & DATE     (931119)
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To determine the tolerance
                          and antiviral response of two different doses
                          of atevirdine mesylate (U-87201E) in
                          symptomatic HIV-positive patients with CD4
                          counts of 50-350 cells/mm3, who also take
                          zidovudine (AZT) at 500-600 mg total daily
                          dose. SECONDARY: To determine time to a
                          10-fold increase in IC50 in patients on
                          U-87201E, time to a 1-log decrease in
                          viremia, and effect on the pharmacokinetics
                          of U-87201E; to determine time to
                          new/recurrent AIDS-defining illness and
                          survival at 1 year. Methodology: Patients are
                          randomized to one of three treatment groups:
                          U-87201E at 200 or 600 mg or placebo
                          administered every 8 hours. Patients must
                          have taken AZT for at least 3 months prior to
                          randomization.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to one
                          of three treatment groups: U-87201E at 200 or
                          600 mg or placebo administered every 8 hours.
                          Patients must have taken AZT for at least 3
                          months prior to randomization.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930831)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive by ELISA
                          confirmed by Western blot, RIA, HIV culture,
                          or another method. 2. Symptomatic (currently
                          or prior to enrollment) for Category B or C
                          of CDC classification, although THE FOLLOWING
                          CURRENT ACUTE MEDICAL CONDITIONS ARE NOT
                          ALLOWED: - Cryptococcosis - Pneumocystis
                          carinii pneumonia - Herpes zoster -
                          Histoplasmosis - CMV - Hepatic or renal
                          disease - Lymphoma. 3. CD4 count 50 - 350
                          cells/mm3 within 14 days prior to study
                          entry. 4. Ongoing therapy with AZT at 500 -
                          600 mg total daily dose for at least 3 months
                          prior to study entry.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    M/3330/0018
STUDY DESIGN              Randomized; Multicenter; Parallel-Group;
                          Double-Blind; Placebo-Controlled; 3-Arm; Dose
                          Comparison; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug tolerance, Drug efficacy,
                          Combination drug therapy, Pharmacokinetics.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 54 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 12 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Symptoms
                          (currently or prior to enrollment) included
                          in Category B or C of CDC classification,
                          although THE FOLLOWING CURRENT ACUTE MEDICAL
                          CONDITIONS ARE NOT ALLOWED: - Cryptococcosis
                          - Pneumocystis carinii pneumonia - Herpes
                          zoster - Histoplasmosis - CMV - Hepatic or
                          renal disease - Lymphoma. 3. CD4 count 50 -
                          350 cells/mm3 within 14 days prior to study
                          entry. 4. Ongoing therapy with AZT at 500 -
                          600 mg total daily dose for at least 3 months
                          prior to study entry. 5. Consent of parent,
                          guardian, or person with power of attorney if
                          less than 18 years of age. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.5 g/dl. (men); >= 9.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 50 - 350 cells/mm3. (
                          100 - 200 - 300 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.5 x ULN. If etiology is
                          unknown. OR <= 5 x ULN if etiology is known.
                          (ULN = upp
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.5 x ULN. If etiology is
                          unknown. OR <= 5 x ULN if etiology is known.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 50 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. Alkaline phosphatase <= 2.5 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT for at least
                          3 months prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Primary or
                          secondary prophylaxis for opportunistic
                          infections.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Present use of excessive
                          alcohol or illicit drugs.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapy within 1 month prior to study
                          entry. 2. Prior U-87201E or any other
                          nonnucleoside antiretroviral medications,
                          including but not limited to nevirapine, TIBO
                          R-82150 or TIBO R-82913, L-697639 or
                          L-696229, U-90152S, or any protease
                          inhibitors. 3. Antiretroviral agents other
                          than AZT within 3 months prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Any other
                          investigational drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Intolerance to
                          AZT. 2. Current diagnosis of malignancy for
                          which systemic therapy will be required
                          during the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0144  U-87201E
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
MANUFACTURERS             Drug 1: The Upjohn Company 7000 Portage Road
                          Kalamazoo, MI 49001 Contact: James VanSweden
                          (616) 323-4696.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 or 600 mg (or
                          placebo) q 8 h for up to 54 weeks. Drug 2:
                          500 - 600 mg daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 600 or 1800 mg. Drug 2:
                          500 - 600 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, compressed
                          tablets. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 54 weeks.
SUPPORTING AGENCY         The Upjohn Company.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
LAST REVISION DATE        930831
ENTRY MONTH               9312
CALIFORNIA                University of Southern California / LAC - USC
                          Medical Cntr 1175 North Cummings Street /
                          5021 Clinic Los Angeles, CA 90033-1079
                          Contact: Novella Quesada (213) 343-8277 OPEN
                          930831.
CALIFORNIA                UCI Medical Center / Division of Infectious
                          Diseases 101 City Drive South / Building 53
                          Route 81 Orange, CA 92668 Contact: Marlene
                          Fugate (714) 456-7612 Contact: Sheila
                          Fitzgibbons (714) 456-7747 OPEN 930831.
CALIFORNIA                Davies Medical Center / Institute for HIV
                          Treatment and Rsch Castro and Duboce Streets
                          San Francisco, CA 94114 Contact: Sue Kelly
                          (415) 565-6153 OPEN 930831.
FLORIDA                   Saint Josephs Hospital / Infectious Disease
                          Research Unit 4600 N Habana Suite 14 Tampa,
                          FL 33614 Contact: Vicki Kenyon (813) 870-4760
                          Contact: (Tampa Gen Hospital) (813) 870-4759
                          OPEN 930831.
MASSACHUSETTS             Boston City Hospital / FGH-1 818 Harrison
                          Avenue / Thorndike Room 209 Boston, MA 02118
                          Contact: Nancy Reinhalter (617) 534-5404 OPEN
                          930831.
MARYLAND                  Johns Hopkins University Hospital Richard
                          Starr Ross Rsch Bldg / 720 Rutland Avenue
                          Room 1159 Baltimore, MD 21205-2196 Contact:
                          Becky Becker (410) 955-4370 OPEN 930831.
NEW JERSEY                Veterans Administration Medical Center /
                          Infectious Disease 285 Tremont Ave East
                          Orange, NJ 07018 Contact: Mayra LaTorre (201)
                          676-1000 X 214OPEN 930831.
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 930831.
RHODE ISLAND              Memorial Hospital of Rhode Island 111
                          Brewster Street Pawtucket, RI 02860 Contact:
                          Francis Betencourt (401) 729-2918 OPEN
                          930831.
 
116
UNIQUE IDENTIFIER         FDA/00578
PROTOCOL ID NUMBERS       FDA 200C
PROTOCOL TITLE            A Multi-Center, Placebo-Controlled,
                          Double-Blind, Randomized Trial Comparing the
                          Activity, Safety, and Tolerance of 1) 400 mg
                          Nevirapine in Combination With 500-600 mg
                          Zidovudine Versus Zidovudine Alone in
                          Asymptomatic HIV-1 Infected Patients With
                          3-24 Months of Prior Zidovudine Therapy and
                          200-500 CD4+ Cells/mm3 and 2) 400 mg
                          Nevirapine Versus Nev
VERSION NUMBER & DATE     (940404)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To compare the effect of
                          nevirapine versus placebo alone or in
                          combination with zidovudine (AZT) on CD4
                          T-cell count and percentage after 3 and 6
                          months of treatment. To evaluate the safety
                          and tolerance of nevirapine alone or in
                          combination with AZT. SECONDARY: To compare
                          the effects of the various treatment
                          combinations on virologic and immunologic
                          markers. Methodology: In Part I, patients who
                          have had prior AZT therapy receive either
                          nevirapine or placebo in combination with
                          AZT. In Part II, patients who are nucleoside
                          naive receive either nevirapine or matching
                          placebo. After 6 months, patients receive
                          open-label nevirapine.
GENERAL DESCRIPTION       METHODOLOGY: In Part I, patients who have had
                          prior AZT therapy receive either nevirapine
                          or placebo in combination with AZT. In Part
                          II, patients who are nucleoside naive receive
                          either nevirapine or matching placebo. After
                          6 months, patients receive open-label
                          nevirapine.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940404)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Asymptomatic HIV-1 infection,
                          with positive serum antibody to HIV-1 as
                          determined by ELISA or Western blot. 2. CD4
                          count 200-500 cells/mm3 within 4-28 days
                          prior to study entry. 3. No conditions
                          indicative of AIDS. 4. Per 04/04/94
                          amendment, NO history of HIV-related
                          oropharyngeal thrush or vaginal candidiasis
                          (UNLESS occurred prior to start of AZT
                          treatment), compatible clinical syndrome with
                          documented response to antifungal therapy,
                          excessive weight loss, persistent fever, or
                          diarrhea. NOTE: Patients with a past or
                          present history of oral hairy leukoplakia
                          lymphadenopathy, night sweats, fatigue,
                          bullous impetigo, and/or HIV-related zoster
                          (shingles) are NOT excluded. 5. If enrolled
                          in Part I, must have tolerated 500-600 mg AZT
                          daily for at least the preceding 3 months but
                          no greater than 24 months (per 04/04/94
                          amendment) prior to study entry OR if
                          enrolled in Part II, must be AZT naive, i.e.,
                          have had < 2 months prior AZT experience that
                          ended more than 6 months prior to study
                          entry.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    1038
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Multicenter; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination and single drug
                          therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 250 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 52 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 18 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic HIV-1 infection, with
                          positive serum antibody to HIV-1 as
                          determined by ELISA or Western blot. 2. CD4
                          count 200-500 cells/mm3 within 4-28 days
                          prior to study entry. 3. No conditions
                          indicative of AIDS. 4. None of the
                          constitutional symptoms that are specifically
                          excluded. 5. Prior AZT for 3-24 months
                          (amended 04/04/94) immediately prior to study
                          entry (Part I) OR no prior AZT (Part II). 6.
                          Consent of parent or guardian if less than 18
                          years of age. NOTE: Co-enrollment in a
                          protocol involving another investigational
                          drug or biologic is not permitted. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.5 g/dl. (men); >= 9.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 80000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000 cells/mm3
                          (without use of leukoproliferative drugs).
                          GGT <= 5 x ULN. Alkaline phosphatase <= 2.5 x
                          ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or agree to use
                          barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required (for patients in
                          Part I): Prior AZT at 500-600 mg daily for at
                          least 3 months but not more than 24 months
                          immediately prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. PCP
                          prophylaxis (trimethoprim-sulfamethoxazole,
                          dapsone, or aerosolized pentamidine), at the
                          discretion of the investigator. 2. Antifungal
                          prophylaxis with oral fluconazole or
                          ketoconazole. 3. Antiviral prophylaxis for
                          herpes simplex virus with <= 1000 mg/day oral
                          acyclovir. 4. Dilantin for prevention and
                          treatment of seizures.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following condition are excluded: History of
                          other clinically important disease (i.e., one
                          that precludes participation in the study).
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Chronic use of alcohol or
                          drugs sufficient to impair compliance with
                          protocol requirements.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          medications other than AZT. Excluded within 4
                          weeks prior to study entry: 1.
                          Immunosuppressive or cytotoxic drugs or other
                          experimental drugs. 2. Systemic
                          glucocorticoids and steroid hormones. 3.
                          Dicumarol, warfarin, and other anticoagulant
                          medications. 4. Cimetidine. 5. Tolbutamide.
                          6. Doxycycline. 7. Chloramphenicol. 8.
                          Phenobarbital and other barbiturates. 9.
                          Foscarnet. 10. Erythromycin. 11.
                          Amoxicillin-clavulanate (Augmentin). 12.
                          Ticarcillin clavulanate (Timentin). 13.
                          Biologic response modifiers (alpha
                          interferon, IL-2, immune modulators).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Investigational drugs other than study drugs.
                          2. Systemic glucocorticoids and steroid
                          hormones. 3. Dicumarol, warfarin, and other
                          anticoagulant medications. 4. Cimetidine. 5.
                          Tolbutamide. 6. Doxycycline. 7.
                          Chloramphenicol. 8. Phenobarbital and other
                          barbiturates. 9. Foscarnet. 10. Erythromycin.
                          11. Amoxicillin-clavulanate (Augmentin). 12.
                          Ticarcillin clavulanate (Timentin). 13.
                          Biologic response modifiers (alpha
                          interferon, IL-2, immune modulators).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy other than limited cutaneous basal
                          cell carcinoma. 2. Psychiatric condition
                          sufficient to impair compliance with protocol
                          requirements.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 1 BI-RG-587
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Boehringer Ingelheim Pharmaceuticals
                          Inc 900 Ridgebury Road / PO Box 368
                          Ridgefield, CT 06877 Contact: David Numberger
                          (203) 798-4700.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or placebo)
                          once daily for 14 days, then 200 mgtwice
                          daily. Drug 2: 500 - 600 mg daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 200 mg for 14 days,
                          then 400 mg. Drug 2: 500 - 600 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
SUPPORTING AGENCY         Boehringer Ingelheim Pharmaceuticals Inc.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pyridines/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        940404
ENTRY MONTH               9312
CALIFORNIA                UCSD Treatment Center 2760 Fifth Avenue /
                          Suite 300 San Diego, CA 92103 Contact: Ron
                          Synder (619) 543-8080 Contact: Candace McIvor
                          (619) 298-0177 OPEN 940404.
CALIFORNIA                Saint Francis Memorial Hospital 900 Hyde
                          Street San Francisco, CA 94109 Contact: Brian
                          Goodroad (415) 353-6218 Contact: Ellen
                          LaPointe (415) 353-6299 OPEN 931207.
DELEWARE                  Wilmington Hospital / Infectious Disease
                          Research Laboratory 501 West 14th Street
                          Wilmington, DE 19801 Contact: Arlene Bincsik
                          (302) 428-2538 OPEN 940404.
FLORIDA                   Dr Goodgame and Hopkins 340 N Maitland Avenue
                          Maitland, FL 32751 Contact: Chuck DeMarzo
                          (407) 647-6000 OPEN 940404.
FLORIDA                   CRI South Florida 1508 San Ignacio Avenue /
                          Suite 200 Coral Gables, FL 33146 Contact:
                          Rick Siclari (305) 667-9296 Contact: Lisa
                          Giordano (305) 667-9296 OPEN 931207.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 931207.
KENTUCKY                  Chandler Medical Center / Dept of Medicine
                          800 Rose Street / Room MN 632 Lexington, KY
                          40536-0084 Contact: Karen Bowen (606)
                          257-5473 Contact: Vernon Hackworth (606)
                          233-6107 OPEN 931207.
MISSOURI                  Kansas City AIDS Research Consortium 2411
                          Holmes Blue IV Kansas City, MO 64108-2792
                          Contact: Gary R. Johnson (816) 235-5366
                          Contact: Dr. Lawrence Dall (816) 235-1964
                          OPEN 940404.
NEW YORK                  CRIA of New York 275 Seventh Avenue / 20th
                          Floor New York, NY 10001 Contact: Bette Smith
                          (212) 924-3934 OPEN 931207.
OHIO                      Medical College of Ohio / Department of
                          Medicine 3000 Arlington Avenue Toledo, OH
                          43699 Contact: Jan Kosmyna (419) 381-3726
                          OPEN 940404.
OKLAHOMA                  Associates in Medical and Mental Health 1560
                          East 21st Street / Suite 210 Tulsa, OK
                          74114-1325 Contact: Virginia Butler (918)
                          743-1000 OPEN 940404.
PENNSYLVANIA              Philadelphia FIGHT 201 North Broad Street /
                          6th Floor Philadelphia, PA 19107 Contact:
                          Carol Graeber (215) 557-8265 OPEN 931207.
SOUTH CAROLINA            Alfred F Burnside Jr M D 1640 St Julian Place
                          Suite 300 Columbia, SC 29204 Contact: John
                          Windham (803) 256-7282 OPEN 940404.
 
117
UNIQUE IDENTIFIER         FDA/00577
PROTOCOL ID NUMBERS       FDA 200B
PROTOCOL TITLE            A Multi-Center, Placebo-Controlled,
                          Double-Blind, Randomized Trial Comparing the
                          Virologic and Immunologic Activities of 400
                          mg Nevirapine in Combination With Zidovudine
                          Versus Zidovudine Alone in Asymptomatic HIV-1
                          Infected Patients With 4-12 Months of Prior
                          Zidovudine Therapy and 200-500 CD4+
                          Cells/mm3.
VERSION NUMBER & DATE     (931027)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To compare the virologic
                          activity (quantitative RNA PCR, quantitative
                          PBMC) of the combination of nevirapine and
                          zidovudine (AZT) versus AZT alone after 3 and
                          6 months of treatment. To compare the effects
                          of these two regimens on CD4 T-cell count and
                          percentage. SECONDARY: To compare and
                          evaluate other markers of immunologic and
                          virologic activity in patients receiving
                          nevirapine/AZT versus AZT alone. To compare
                          the effects of the two regimens on clinical
                          signs and symptoms. To evaluate the safety
                          and tolerance of the two regimens.
                          Methodology: Patients receive combination
                          nevirapine/AZT or AZT alone. Patients are
                          evaluated for virologic and immunologic
                          activity at 3 and 6 months.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive combination
                          nevirapine/AZT or AZT alone. Patients are
                          evaluated for virologic and immunologic
                          activity at 3 and 6 months.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930901)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Asymptomatic HIV infection
                          confirmed by ELISA or Western blot. 2. CD4
                          count 200-500 cells/mm3 for two consecutive
                          samples drawn at least 2 days apart during
                          the screening period. 3. No prior AIDS. 4. No
                          history of or active HIV-related thrush,
                          vaginal candidiasis, zoster (shingles),
                          excessive weight loss, persistent fever, or
                          diarrhea. 5. Have tolerated 500-600 mg AZT
                          daily for at least 4 months but no more than
                          12 months immediately prior to study entry.
ELIGIBILITY               ASYM.
OTHER PROTOCOL NUMBERS    BIPI 1037
STUDY DESIGN              Multicenter; Placebo-Controlled;
                          Double-Blind; Randomized; Comparative; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Combination and
                          single drug therapy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients. (Twelve
                          patients at each of five sites)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 6
                          months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic HIV infection. 2. CD4
                          count 200-500 cells/mm3. 3. No prior AIDS. 4.
                          No history of or active HIV-related thrush,
                          vaginal candidiasis, zoster (shingles),
                          excessive weight loss, persistent fever, or
                          diarrhea. 5. Tolerated 500-600 mg AZT daily
                          for at least 4 months but no more than 12
                          months immediately prior to study entry. 6.
                          Consent of parent or guardian if less than 18
                          years of age. NOTE: Patients may not
                          co-enroll in another protocol involving other
                          investigational drugs or biologics. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 9.5 g/dl. (men); >= 9.0 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 80000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 80.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000 cells/mm3
                          (without use of leukoproliferative drugs).
                          GGT <= 5 x ULN. Alkaline phosphatase <= 2.5 x
                          ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: AZT at 500-600
                          mg/day for at least 4 months but no more than
                          12 months immediately preceding study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. PCP
                          prophylaxis (trimethoprim-sulfamethoxazole,
                          dapsone, or aerosolized pentamidine), at the
                          discretion of the investigator. 2. Antifungal
                          prophylaxis with oral fluconazole or
                          ketoconazole. 3. Antiviral prophylaxis for
                          herpes simplex virus with <= 1000 mg/day oral
                          acyclovir. 4. Dilantin for prevention and
                          treatment of seizures.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of clinically important disease other
                          than HIV infection, that may put patient at
                          risk because of participation in this study.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use barrier methods of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Chronic use of alcohol or
                          drugs sufficient to impair study compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Antiretroviral
                          medications other than AZT. Excluded within 4
                          weeks prior to study entry: 1.
                          Immunosuppressive or cytotoxic drugs or other
                          experimental drugs. 2. Systemic
                          glucocorticoids and steroid hormones. 3.
                          Dicumarol, warfarin, and other anticoagulant
                          medications. 4. Cimetidine. 5. Tolbutamide.
                          6. Doxycycline. 7. Chloramphenicol. 8.
                          Phenobarbital and other barbiturates. 9.
                          Foscarnet. 10. Erythromycin. 11.
                          Amoxicillin-clavulanate (augmentin). 12.
                          Ticarcillin clavulanate. 13. Biologic
                          response modifiers (alpha interferon, IL-2,
                          immune modulators).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          glucocorticoids and steroid hormones. 2.
                          Dicumarol, warfarin, and other anticoagulant
                          medications. 3. Cimetidine. 4. Tolbutamide.
                          5. Doxycycline. 6. Chloramphenicol. 7.
                          Phenobarbital and other barbiturates. 8.
                          Foscarnet. 9. Erythromycin. 10.
                          Amoxicillin-clavulanate (Augmentin). 11.
                          Ticarcillin clavulanate. 12. Biologic
                          response modifiers (alpha interferon, IL-2,
                          immune modulators). 13. Any investigational
                          drugs other than study drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy other than limited cutaneous basal
                          cell carcinoma. 2. Psychiatric condition
                          sufficient to impair study compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0116  Nevirapine
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 1 BI-RG-587
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Boehringer Ingelheim Pharmaceuticals
                          Incorporated 90 East Ridge / PO Box 368
                          Ridgefield, CT 06877 Contact: Dr Inder Kaul
                          (203) 791-6215.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 400 mg daily for at
                          least 6 months. Drug 2: 500 - 600 mg daily
                          for at least 6 months
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 400 mg. Drug 2: 500 -
                          600 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 6 months.
SUPPORTING AGENCY         Boehringer Ingelheim Pharmaceuticals
                          Incorporated.
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Pyridines/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       129618-40-2 (BI-RG 587)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        930901
ENTRY MONTH               9312
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 930901 ACTU: 0808.
ILLINOIS                  Northwestern Univ Medical School / Comp AIDS
                          Ctr / Infec Dis 303 East Superior Street /
                          Passavant Room 823 Chicago, IL 60611 Contact:
                          Baiba Berzins (312) 908-9636 OPEN 930901.
MARYLAND                  Johns Hopkins University Hospital 1830 E
                          Monument St \ 8th Floor Baltimore, MD 21205
                          Contact: Louis Grue (410) 955-2898 OPEN
                          931013.
MISSOURI                  Washington University School of Medicine
                          Campus Box 8011 / 4511 Forest Park Parkway /
                          Suite 304 St Louis, MO 63108 Contact: Dr
                          William Powderly (314) 361-5231 Contact: Mark
                          Myers (314) 454-0058 OPEN 930901.
 
118
UNIQUE IDENTIFIER         FDA/00555
PROTOCOL ID NUMBERS       FDA 136A
PROTOCOL TITLE            Study of the Activity of Thymic Humoral
                          Factor (THF gamma 2) on HIV Load in
                          HIV-Positive Individuals With CD4+ Cell
                          Counts in the Range of 200-500 Cells/mm3.
VERSION NUMBER & DATE     (940420)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To investigate the safety of thymic
                          humoral factor (THF gamma 2), its effect on
                          HIV load based on at least a 75 percent
                          decrease in HIV quantitative PCR RNA
                          copies/ml, and its persistence when
                          administered in combination with an
                          antiretroviral nucleoside derivative
                          (zidovudine; AZT). To assess the effects of
                          THF gamma 2 on T-cells, quality of life, and
                          progression of disease. Methodology: All
                          patients receive 12 weeks of AZT before being
                          randomized to self-administer one of two
                          doses of THF gamma 2 (500 ng or 40 mcg) or
                          placebo for 15 consecutive days and then
                          twice weekly for an additional 50 weeks.
GENERAL DESCRIPTION       METHODOLOGY: All patients receive 12 weeks of
                          AZT before being randomized to
                          self-administer one of two doses of THF gamma
                          2 (500 ng or 40 mcg) or placebo for 15
                          consecutive days and then twice weekly for an
                          additional 50 weeks.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (931105)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive by ELISA
                          confirmed by Western blot. 2. Either
                          asymptomatic or with persistent generalized
                          lymphadenopathy (PGL). 3. No history of
                          symptoms in Category B or C of 1993 Case
                          Definition, other than oral candidiasis
                          following previous broad-spectrum antibiotic
                          therapy. 3. Mean CD4 of 200-500 cells/mm3 for
                          counts taken at 4, 3, and 1 weeks prior to
                          study entry. (At least two counts must be
                          within range of 200-500 cells/mm3; other
                          count must be within range of 150-600
                          cells/mm3.) AMENDED 04/20/94: AZT-treated
                          patients need have only one CD4 count 200 -
                          500 cells/mm3 within 7 days prior to
                          randomization. 4. HIV-1 positive PCR RNA.
ELIGIBILITY               ASYM. PGL.
OTHER PROTOCOL NUMBERS    CS 112010-999
STUDY DESIGN              Randomized; Double-Blind; Placebo-Controlled;
                          Multicenter; Dose Comparison; Drug
                          Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 64 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 10 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity and be either
                          asymptomatic or have persistent generalized
                          lymphadenopathy (PGL). 2. No history of
                          symptoms in Category B or C of 1993 Case
                          Definition, other than oral candidiasis
                          following previous broad-spectrum antibiotic
                          therapy. 3. Mean CD4 of 200-500 cells/mm3. 4.
                          HIV-1 positive PCR RNA. 5. Ability to
                          self-administer study drug by IM injection.
                          6. Ability to tolerate AZT at 600 mg daily
                          during first 8 weeks of run-in period (if AZT
                          naive) OR tolerated AZT at >= 500 mg daily
                          for at least 3 months but no more than 12
                          months prior to randomization. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 2.5 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 90.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 5 x ULN.
                          Creatine phosphokinase <= 2 x ULN. Absolute
                          neutrophils >= 1000 cells/mm3. PT <= 1.25 x
                          ULN. PTT <= 1.6 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. AZT or
                          another antiretroviral agent (marketed or
                          investigational under a Treatment IND). 2.
                          Primary prophylaxis for Pneumocystis carinii
                          pneumonia (PCP), toxoplasmosis, and
                          Mycobacterium avium-intracellulare (MAI) if
                          patient's CD4 count decreases to < 200
                          cells/mm3. 3. Other marketed drugs as
                          required.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Myositis within the past 6 months. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active alcoholism, drug abuse,
                          or a mental or psychiatric problem sufficient
                          to prevent adequate compliance with study.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 6 weeks
                          prior to study entry: Blood transfusion or
                          blood products.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Experimental
                          therapy, including interleukin-2, interferon,
                          erythropoietin, or filgastrim nucleoside
                          within 6 weeks prior to study entry. 2. Prior
                          antiretroviral therapy (AZT-naive patients
                          only).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Non-antiretroviral agents with known or
                          suspected activity against HIV. 2.
                          Investigational new drugs that are not
                          antiretroviral agents distributed under a
                          Treatment IND.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy. 2. Hematuria. 3. Proteinuria >
                          1+.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0187  Thymic humoral factor (THF
                          gamma 2)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
TRADE NAME OF SUBSTANCE   Drug 2 Retrovir
MANUFACTURERS             Drug 1: Adria Laboratories PO Box 16529
                          Columbus, OH 43216-6529 Contact: Dr Robert
                          Nolan (614) 764-8192.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 500 ng or 40 mcg (or
                          placebo) daily for 15 days, then twice weekly
                          for 50 weeks. Drug 2: 600 mg daily for 12
                          weeks prior to randomization to THFplacebo
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 500 ng or 40 mcg. Drug
                          2: 600 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intramuscular (IM)
SUPPORTING AGENCY         Adria Laboratories.
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Oligopeptides/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       107489-37-2 (thymic humoral factor gamma 2)
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
LAST REVISION DATE        931105
ENTRY MONTH               9309
CALIFORNIA                SW Community Based AIDS Treatment
                          Group-COMBAT 1800 North Highland Avenue /
                          Suite 610 Los Angeles, CA 90028 Contact:
                          Holly Boyd (213) 469-5888 Contact: Stacey
                          Kobayashi (213) 469-5888 OPEN 931105.
CALIFORNIA                Michael S Gottleib M D 4929 Van Nuys
                          Boulevard Sherman Oaks, CA 91403 Contact:
                          Renee Potochan (818) 501-2600 OPEN 931105.
CALIFORNIA                University of California Medical Science
                          1-C240 Irvine, CA 92717 Contact: Pat Hunter
                          (714) 856-8334 OPEN 940527.
CALIFORNIA                San Francisco Veterans' Administration
                          Medical Center 4150 Clement Street #111W San
                          Francisco, CA 94121 Contact: Manon Marovich
                          (415) 221-4810 X 394Contact: Sandra Charles
                          (415) 221-4810 X 394OPEN 931105 ACTU: 0807.
FLORIDA                   Dr Goodgame and Hopkins 340 N Maitland Avenue
                          Maitland, FL 32751 Contact: Chuck DeMarzo
                          (407) 647-6000 OPEN 930811.
FLORIDA                   Memorial Hospital Hollywood 4700 K Sheridan
                          Street Hollywood, FL 33021 Contact: Sherry
                          Balder (305) 962-0040 Contact: (305) 987-2000
                          OPEN 940527.
NEW YORK                  Chelsea Village Medical Center 314 West 14th
                          Street / 5th Floor New York, NY 10014
                          Contact: Pat Costello (212) 620-0145 OPEN
                          940527.
OREGON                    The Research and Education Group 2701 NW
                          Vaughn / Suite 770 Portland, OR 97210
                          Contact: Robin Larson (503) 229-8428 OPEN
                          931105.
SOUTH CAROLINA            Alfred F Burnside Jr M D 1640 St Julian Place
                          Suite 300 Columbia, SC 29204 Contact: John
                          Windham (803) 256-7282 OPEN 930811.
 
119
UNIQUE IDENTIFIER         FDA/00544
PROTOCOL ID NUMBERS       FDA 134C
PROTOCOL TITLE            Open Trial of DOX-SL (Stealth Liposomal
                          Doxorubicin Hydrochloride) in the Treatment
                          of Moderate to Severe AIDS-Related Kaposi's
                          Sarcoma.
VERSION NUMBER & DATE     (930625)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and
                          effectiveness of Stealth liposomal
                          doxorubicin hydrochloride (DOX-SL) in the
                          long-term treatment of AIDS-related Kaposi's
                          sarcoma (KS) in patients who previously had
                          good responses to DOX-SL in controlled
                          studies of limited duration, or those with KS
                          who discontinued treatment with another
                          Kaposi's sarcoma therapy because of
                          inadequate efficacy or unacceptable toxicity.
                          To provide a defined protocol for Kaposi's
                          sarcoma patients for whom DOX-SL therapy is
                          indicated. Methodology: Patients receive 20
                          mg/m2 DOX-SL every 3 weeks for a maximum of
                          20 cycles (including any cycles from a
                          previous DOX-SL study). KS lesions are
                          evaluated prior to administration of each
                          treatment, at the end of the final treatment
                          cycle, and at 4 weeks following the end of
                          the final treatment. Patients who respond
                          will be followed every 2 months for up to 1
                          year. Study treatment may be interrupted for
                          up to 4 months because of complete response,
                          development of opportunistic infections, or
                          adverse drug effects.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive 20 mg/m2 DOX-SL
                          every 3 weeks for a maximum of 20 cycles
                          (including any cycles from a previous DOX-SL
                          study). KS lesions are evaluated prior to
                          administration of each treatment, at the end
                          of the final treatment cycle, and at 4 weeks
                          following the end of the final treatment.
                          Patients who respond will be followed every 2
                          months for up to 1 year. Study treatment may
                          be interrupted for up to 4 months because of
                          complete response, development of
                          opportunistic infections, or adverse drug
                          effects.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940520)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS-related Kaposi's sarcoma
                          of a severity requiring systemic
                          chemotherapy. 2. Anti-HIV antibody on ELISA
                          confirmed by an appropriate validation
                          method. 3. No active opportunistic infection
                          with mycobacteria, cytomegalovirus,
                          toxoplasma, Pneumocystis carinii, or other
                          microorganisms (if under treatment with
                          myelotoxic drugs). NOTE: Eligible KS patients
                          include those who have discontinued therapy
                          in the control arm of a DOX-SL KS study
                          because of side effects or inadequate
                          efficacy OR other KS patients for whom DOX-SL
                          is believed to be indicated. Patients must
                          not be eligible for other Liposome Technology
                          protocols comparing DOX-SL with established
                          therapies.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    LTI-30-12
STUDY DESIGN              Open Label; Noncomparative
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: UNLIMITED patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 33 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Moderate to severe AIDS-related
                          Kaposi's sarcoma. 2. Documented anti-HIV
                          antibody. 3. No active opportunistic
                          infection with mycobacteria, cytomegalovirus,
                          toxoplasma, Pneumocystis carinii, or other
                          microorganisms (if under treatment with
                          myelotoxic drugs). NOTE: Eligible KS patients
                          include those who have discontinued therapy
                          in the control arm of a DOX-SL KS study
                          because of side effects or inadequate
                          efficacy OR other KS patients for whom DOX-SL
                          is believed to be indicated. Patients must
                          not be eligible for other Liposome Technology
                          protocols comparing DOX-SL with established
                          therapies. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 40.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 1200 cells/mm3. PT < 2 x
                          ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Prophylaxis for PCP, cryptococcal, and herpes
                          infections, and antiretroviral therapy
                          provided these doses have been stable for at
                          least 1 month. 2. Maintenance therapy for
                          tuberculosis, fungal, and herpes infections.
                          3. Therapy for new episodes of tuberculosis,
                          fungal, and herpes infections except with
                          potentially myelotoxic chemotherapy. 4.
                          Foscarnet or ganciclovir for CMV infection.
                          5. Colony stimulating factors and
                          erythropoietin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior neoplasms treated with extensive
                          chemotherapy that, in the investigator's
                          opinion, has led to an irreversibly
                          compromised marrow function. 2. History of
                          idiosyncratic or allergic reaction to
                          anthracyclines. 3. History of major
                          psychiatric illness. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within the past 3
                          weeks: Radiation or electron beam therapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within the past 4
                          weeks: 1. Cytotoxic chemotherapy (other than
                          in a qualifying Liposome Technology
                          protocol). 2. Interferon treatment.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Other
                          cytotoxic cancer chemotherapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Clinically significant cardiac disease. 2.
                          Confusion or disorientation.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Must not be eligible for other
                          Liposome Technology protocols comparing DOXIL
                          with established therapies.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0185  Doxorubicin hydrochloride
                          (liposomal)
TRADE NAME OF SUBSTANCE   Drug 1 DOX-SL
MANUFACTURERS             Drug 1: Liposome Technology Incorporated 1050
                          Hamilton Court Menlo Park, CA 94025 Contact:
                          Melody Anderson (415) 323-9011.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 20 mg/m2 over 30 min
                          q 3 months for a maximum of twenty3-month
                          cycles (including any cycles from a previous
                          study)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, vials
OTHER TREATMENT INFO.     TREATMENT DURATION: Maximum of twenty 3-week
                          treatment cycles (including any cycles from a
                          previous study).
SUPPORTING AGENCY         Liposome Technology Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Doxorubicin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Carriers
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Liposomes
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/*DRUG THERAPY/ETIOLOGY
CAS REGISTRY NUMBER       0 (Drug Carriers)
CAS REGISTRY NUMBER       0 (Liposomes)
CAS REGISTRY NUMBER       23214-92-8 (Doxorubicin)
LAST REVISION DATE        940520
ENTRY MONTH               9307
CALIFORNIA                Dr Becky Miller 8621 West Third Street Suite
                          600E Los Angeles, CA 90048 Contact: Jean
                          Klein (310) 854-5841 OPEN 940520.
CALIFORNIA                Pacific Oaks Medical Group 150 N Robertson
                          Suite 300 Beverly Hills, CA 90211 Contact:
                          Rod Raphael (310) 652-2562 OPEN 940520.
CALIFORNIA                Pacific Oaks Medical Group 4940 Van Nuys Blvd
                          Sherman Oaks, CA 91403 Contact: Rod Raphael
                          (310) 652-2562 OPEN 940520.
CALIFORNIA                Tarzana Medical Center 16133 Ventura
                          Boulevard Suite 470 Encino, CA 91436 Contact:
                          Mary Hillner (818) 981-4156 OPEN 940520.
CALIFORNIA                Apogee Medical Group 3415 Sixth Avenue SW San
                          Diego, CA 92103 Contact: Steve Anderson (619)
                          295-4448 OPEN 940520.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: Carol Arri (415)
                          476-9296 X 840OPEN 940520.
CALIFORNIA                Kaiser Permanente / HIV Research Unit 2590
                          Geary Boulevard San Francisco, CA 94115
                          Contact: Kate Fitzgerald (415) 202-3480 OPEN
                          940520.
CALIFORNIA                University of California/San Francisco 350
                          Parnassus Avenue Suite 701 San Francisco, CA
                          94117 Contact: Anita Harrison (415) 566-3431
                          OPEN 940520.
CALIFORNIA                VA San Francisco Hematology/Oncology Clinic
                          4150 Clement Street 111H1 San Francisco, CA
                          94121 Contact: Anita Harrison (415) 502-0873
                          OPEN 940520.
CALIFORNIA                Univrsity of California/San Francisco 400
                          Parnassus Avenue 5th Floor Room A502 San
                          Francisco, CA 94143-0324 Contact: Julie
                          Russel (415) 476-8911 OPEN 940520.
CALIFORNIA                East Bay AIDS Clinic 3031 Telegraph Avenue
                          Berkeley, CA 94705 Contact: Nancy Orcutt
                          (510) 204-1870 OPEN 940520.
DISTRICT OF COLUMBIA      Dr Mahmoud Mustafa 2311 M Street Suite 401
                          Washington, DC 20037 Contact: Cathi Carlise
                          (202) 331-3762 OPEN 940520.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue 1st Floor Eliot Building
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 OPEN 940520.
FLORIDA                   H Lee Moffit Cancer Center and Research
                          Institute 12902 Magnolia Drive Tampa, FL
                          33612 Contact: Jeane Richard (813) 972-8477
                          OPEN 940520.
GEORGIA                   American Medical Research Institute 1677
                          Tullie Circle Suite 118 Atlanta, GA 30329
                          Contact: Jane Green (404) 395-0009 OPEN
                          940520.
GEORGIA                   Infectious Disease Consortium Southeast
                          Clinical Resources 1758 Century Boulevard
                          Suite A Atlanta, GA 30345 Contact: Kim Prieto
                          (404) 388-3694 OPEN 940520.
ILLINOIS                  Northwestern Medical Faculty Foundation 233
                          East Erie Suite 700 Chicago, IL 60611
                          Contact: Rebecca Sunenshine (312) 908-2250
                          OPEN 940520.
ILLINOIS                  Rush Presbyterian Medical College 1725 W
                          Harrison Room 809 Chicago, IL 60612 Contact:
                          Jean Lydon (312) 942-5904 OPEN 940520.
ILLINOIS                  Illinois Masonic Medical Center The Cancer
                          Center 900 West Belmont Avenue Chicago, IL
                          60657 Contact: Helen Gereas (312) 296-7089
                          OPEN 940520.
MICHIGAN                  Henry Ford Medical Center Division of
                          Hematology/Oncology 2799 West Grand Boulevard
                          13th Floor Room 1305 Detroit, MI 48202
                          Contact: Carolyn Schmidt (313) 876-7277 OPEN
                          940520.
MISSOURI                  Washington University 660 South Euclid B8125
                          St Louis, MO 63108 Contact: Mary Gould (314)
                          454-0058 OPEN 940520.
NEW YORK                  St Vincent's Hospital and Medical Center 412
                          Sixth Avenue Suite 401 New York, NY 10011
                          Contact: Mary Catherine George (212) 228-4633
                          OPEN 940520.
NEW YORK                  New York University Medical Center 530 First
                          Avenue New York, NY 10016 Contact: Therese
                          Powers (212) 263-6485 OPEN 940520.
NEW YORK                  Memorial Sloan-Kettering Cancer Center Box
                          306 1275 York Avenue New York, NY 10021
                          Contact: Michael Pino (212) 639-7161 OPEN
                          940520.
NEW YORK                  St Luke's-Roosevelt Hospital Center 126 West
                          60th Street New York, NY 10023 Contact: Diana
                          Mott-Tierno (212) 316-9689 OPEN 940520.
NEW YORK                  Mt Sinai Hospital One Gustave Levy Place Box
                          1042 New York, NY 10029 Contact: Eileen
                          Chusid (212) 241-8903 Contact: Alice Mercado
                          (212) 241-8903 OPEN 940520.
NEW YORK                  Roswell Park Cancer Institute Elm and Carlton
                          Street Buffalo, NY 14263 Contact: Paula
                          Grimes (716) 845-8965 OPEN 940520.
PENNSYLVANIA              The Tuttleman Center Graduate Hospital 1840
                          South Street 2nd floor Philadelphia, PA 19146
                          Contact: Barbara Rensman (215) 893-7541 OPEN
                          940520.
 
120
UNIQUE IDENTIFIER         FDA/00543
PROTOCOL ID NUMBERS       FDA 134B
PROTOCOL TITLE            Randomized, Comparative Trial of DOX-SL
                          (Stealth Liposomal Doxorubicin Hydrochloride)
                          Versus Bleomycin and Vincristine in the
                          Treatment of AIDS-Related Kaposi's Sarcoma.
VERSION NUMBER & DATE     (930625)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To determine the efficacy of Stealth
                          liposomal doxorubicin hydrochloride (DOX-SL)
                          in the treatment of moderate to severe
                          AIDS-related Kaposi's sarcoma (KS) by
                          comparison with the established therapy BV
                          (bleomycin/vincristine). To evaluate the
                          safety and tolerance of DOX-SL compared to BV
                          in a population of AIDS patients with
                          moderate to severe KS. Methodology: Patients
                          are randomized to receive either DOX-SL or
                          the BV combination. Infusions are given on
                          day 1 and every 3 weeks for a total of six
                          cycles. Kaposi's sarcoma lesions are
                          evaluated prior to every cycle, at the end of
                          the last treatment cycle, and 4 weeks
                          following the end of the last treatment.
                          Patients who respond to therapy will be
                          followed every 2 months for up to 1 year.
                          Patients must agree to have one or more
                          representative KS lesions biopsied.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either DOX-SL or the BV combination.
                          Infusions are given on day 1 and every 3
                          weeks for a total of six cycles. Kaposi's
                          sarcoma lesions are evaluated prior to every
                          cycle, at the end of the last treatment
                          cycle, and 4 weeks following the end of the
                          last treatment. Patients who respond to
                          therapy will be followed every 2 months for
                          up to 1 year. Patients must agree to have one
                          or more representative KS lesions biopsied.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940520)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Biopsy-proven, progressive,
                          AIDS-related Kaposi's sarcoma, with any of
                          the following: - At least 15 mucocutaneous
                          lesions. - Six or more new lesions in the
                          prior month. - Documented visceral disease
                          with at least five accessible cutaneous
                          lesions. 2. Anti-HIV antibody by ELISA
                          confirmed by an appropriate validation
                          method. 3. No active opportunistic infection
                          with mycobacteria, cytomegalovirus,
                          toxoplasma, Pneumocystis carinii, or other
                          microorganisms (if REQUIRING treatment with
                          myelotoxic drugs). NOTE: Patients who fail
                          the BV combination or who relapse are
                          eligible to enter the Liposome Technology
                          open trial using DOX-SL alone.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    LTI-30-11
STUDY DESIGN              2-Arm; Prospective; Randomized; Multicenter;
                          Comparative; Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination drug therapy,
                          Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 220 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Biopsy-proven, progressive,
                          AIDS-related Kaposi's sarcoma, with any of
                          the following: - At least 15 mucocutaneous
                          lesions. - Six or more new lesions in the
                          prior month. - Documented visceral disease
                          with at least five accessible cutaneous
                          lesions. 2. Documented anti-HIV antibody. 3.
                          No active opportunistic infection with
                          mycobacteria, cytomegalovirus, toxoplasma,
                          Pneumocystis carinii, or other microorganisms
                          (if REQUIRING treatment with myelotoxic
                          drugs). 4. Life expectancy > 4 months. NOTE:
                          Patients who fail the BV combination or who
                          relapse are eligible to enter the Liposome
                          Technology open trial using DOX-SL alone.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   CREATININE: < 2 x ULN.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 30.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 1500 cells/mm3. PT < 2 x
                          ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Prophylaxis for PCP, cryptococcal, and herpes
                          infections, and antiretroviral therapy (e.g.,
                          AZT, ddC, ddI) provided these doses have been
                          stable for at least 1 month. 2. Maintenance
                          therapy for tuberculosis, fungal, and herpes
                          infections. 3. Therapy for new episodes of
                          tuberculosis, fungal, and herpes infection
                          except with potentially myelotoxic
                          chemotherapy. 3. Foscarnet for
                          cytomegalovirus infection. 4. Erythropoietin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior neoplasms treated with extensive
                          chemotherapy that, in the investigator's
                          opinion, has led to irreversibly compromised
                          bone marrow function. 2. History of
                          idiosyncratic or allergic reaction to
                          anthracyclines, bleomycin, or vincristine. 3.
                          History of major psychiatric illness. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation or
                          electron beam therapy within the past 3
                          weeks.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Cytotoxic
                          chemotherapy or interferon therapy within the
                          past 4 weeks. 2. More than one prior cycle of
                          bleomycin/vincristine at any time.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          cytotoxic chemotherapy. 2. Colony-stimulating
                          factors. 3. Ganciclovir.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Clinically significant cardiac disease. 2.
                          Confusion, disorientation, CNS symptoms, or
                          peripheral neuropathy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0185  Doxorubicin hydrochloride
                          (liposomal)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0045  Bleomycin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0046  Vincristine
TRADE NAME OF SUBSTANCE   Drug 1 DOX-SL
MANUFACTURERS             Drug 1: Liposome Technology Incorporated 1050
                          Hamilton Court Menlo Park, CA 94025 Contact:
                          Melody Anderson (415) 323-9011.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 20 mg/m2 over 30 min
                          on day 1 and q 3 weeks for a totalof six
                          cycles. Drug 2: 15 mg/m2 over 1 hr on day 1
                          and q 3 weeks for a total ocycles. Drug 3:
                          1.4 mg/m2 by bolus injection on day 1 and q 3
                          weeks fortotal of six cycles. Should be
                          administered prior to bleomycin
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, vials.
                          Drug 2: Intravenous. Drug 3: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: 18 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Unacceptable
                          toxicity.
SUPPORTING AGENCY         Liposome Technology Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Bleomycins/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Doxorubicin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Carriers
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Liposomes
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/*DRUG THERAPY/ETIOLOGY
MESH HEADING              Vincristine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Bleomycins)
CAS REGISTRY NUMBER       0 (Drug Carriers)
CAS REGISTRY NUMBER       0 (Liposomes)
CAS REGISTRY NUMBER       23214-92-8 (Doxorubicin)
CAS REGISTRY NUMBER       57-22-7 (Vincristine)
LAST REVISION DATE        940520
ENTRY MONTH               9308
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Bosotn, MA 02215 Contact: Paul Marcoux (617)
                          735-4700 X 152OPEN 940520.
NEW YORK                  Mt Sinai Hospital One Gustave Levy Place Box
                          1042 New York, NY 10029 Contact: Eileen
                          Chusid (212) 241-8903 Contact: Alice Mercado
                          (212) 241-8903 OPEN 940520.
 
121
UNIQUE IDENTIFIER         FDA/00542
PROTOCOL ID NUMBERS       FDA 134A
PROTOCOL TITLE            Randomized, Comparative Trial of DOX-SL
                          (Stealth Liposomal Doxorubicin Hydrochloride)
                          Versus Adriamycin, Bleomycin, and Vincristine
                          (ABV) in the Treatment of Severe AIDS-Related
                          Kaposi's Sarcoma.
VERSION NUMBER & DATE     (930625)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To determine the efficacy of Stealth
                          liposomal doxorubicin hydrochloride (DOX-SL)
                          in the treatment of severe AIDS-related
                          Kaposi's sarcoma (KS) by comparison with the
                          established therapy ABV: Adriamycin
                          (doxorubicin)/bleomycin/vincristine. To
                          evaluate the safety and tolerance of DOX-SL
                          compared to ABV in a population of AIDS
                          patients with severe KS. Methodology:
                          Patients are randomized to receive either
                          DOX-SL or the ABV combination. Infusions are
                          given on day 1 and every 2 weeks for a total
                          of six cycles. Kaposi's sarcoma lesions are
                          evaluated prior to every cycle, at the end of
                          the last treatment cycle, and 4 weeks
                          following the end of the last treatment.
                          Patients must agree to have one or more
                          representative KS lesions biopsied.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either DOX-SL or the ABV combination.
                          Infusions are given on day 1 and every 2
                          weeks for a total of six cycles. Kaposi's
                          sarcoma lesions are evaluated prior to every
                          cycle, at the end of the last treatment
                          cycle, and 4 weeks following the end of the
                          last treatment. Patients must agree to have
                          one or more representative KS lesions
                          biopsied.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940520)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Biopsy-proven, progressive,
                          AIDS-related Kaposi's sarcoma, with any of
                          the following: - At least 25 mucocutaneous
                          lesions. - Ten or more new lesions in the
                          prior month. - Documented visceral disease
                          with at least two accessible cutaneous
                          lesions. - Two accessible cutaneous lesions
                          with edema. 2. Anti-HIV antibody by ELISA
                          confirmed by an appropriate validation
                          method. 3. No active opportunistic infection
                          with mycobacteria, cytomegalovirus,
                          toxoplasma, Pneumocystis carinii, or other
                          microorganisms (if under treatment with
                          myelotoxic drugs). NOTE: Patients who respond
                          to therapy on this protocol, as well as those
                          who fail the ABV combination, are eligible to
                          enter the Liposome Technology open trial
                          using DOX-SL alone.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    LTI-30-10
STUDY DESIGN              2-Arm; Prospective; Randomized; Multicenter;
                          Comparative; Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Combination drug therapy,
                          Comparative drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 225 patients.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 28 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Biopsy-proven, progressive,
                          AIDS-related Kaposi's sarcoma, with any of
                          the following: - At least 25 mucocutaneous
                          lesions. - Ten or more new lesions in the
                          prior month. - Documented visceral disease
                          with at least two accessible cutaneous
                          lesions. - Two accessible cutaneous lesions
                          with edema. 2. Documented anti-HIV antibody.
                          3. No active opportunistic infection with
                          mycobacteria, cytomegalovirus, toxoplasma,
                          Pneumocystis carinii, or other microorganisms
                          (if under treatment with myelotoxic drugs).
                          4. Life expectancy > 4 months. NOTE: Patients
                          who respond to therapy on this protocol, as
                          well as those who fail the ABV combination,
                          are eligible to enter the Liposome Technology
                          open trial using DOX-SL alone. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50. (or >= 40 if decreased
                          performance status is directly attributable
                          to the KS).
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 1200 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Prophylaxis for PCP, cryptococcal, and herpes
                          infections, and antiretroviral therapy (e.g.,
                          AZT, ddC, ddI) provided these doses have been
                          stable for at least 1 month. 2. Therapy for
                          tuberculosis, fungal, and herpes infections
                          except with potentially myelotoxic
                          chemotherapy. 3. Foscarnet for new episodes
                          of cytomegalovirus infection. 4.
                          Colony-stimulating factors and
                          erythropoietin.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Prior neoplasms treated with extensive
                          chemotherapy that, in the investigator's
                          opinion, has led to irreversibly compromised
                          bone marrow function. 2. History of
                          idiosyncratic or allergic reaction to
                          bleomycin or vincristine. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiation or
                          electron beam therapy within the past 3
                          weeks.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          anthracycline therapy. 2. Cytotoxic
                          chemotherapy or interferon treatment within
                          the past 4 weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          cytotoxic chemotherapy. 2. Ganciclovir.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Clinically significant cardiac, hepatic, or
                          renal disease. 2. Peripheral neuropathy,
                          signs of moderate to severe sensory loss, or
                          moderate to marked motor loss. 3. Inability
                          to comply with the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0185  Doxorubicin hydrochloride
                          (liposomal)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0047  Doxorubicin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0046  Vincristine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0045  Bleomycin
TRADE NAME OF SUBSTANCE   Drug 1 DOX-SL
TRADE NAME OF SUBSTANCE   Drug 2 Adriamycin
MANUFACTURERS             Drug 1: Liposome Technology Incorporated 1050
                          Hamilton Court Menlo Park, CA 94025 Contact:
                          Melody Anderson (415) 323-9011.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 20 mg/m2 over 30 min
                          on day 1 and q 2 weeks for a totalof six
                          cycles. Drug 2: 20 mg/m2 over at least 3-5
                          min on day 1 and q 2 weeks ftotal of six
                          cycles. Should be administered prior to
                          bleomycin.Drug 3: 1.0 mg over 1 min on day 1
                          and q 2 weeks for a total ofcycles. Should be
                          administered prior to bleomycin. Drug 4: 10
                          mg/m2 over 10 min on day 1 and q 2 weeks for
                          a totalsix cycles
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous, vials.
                          Drug 2: Intravenous. Drug 3: Intravenous.
                          Drug 4: Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: 12 weeks.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Unacceptable
                          toxicity.
SUPPORTING AGENCY         Liposome Technology Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Bleomycins/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Doxorubicin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Carriers
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Liposomes
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/*DRUG THERAPY/ETIOLOGY
MESH HEADING              Vincristine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Bleomycins)
CAS REGISTRY NUMBER       0 (Drug Carriers)
CAS REGISTRY NUMBER       0 (Liposomes)
CAS REGISTRY NUMBER       23214-92-8 (Doxorubicin)
CAS REGISTRY NUMBER       57-22-7 (Vincristine)
LAST REVISION DATE        940520
ENTRY MONTH               9307
CALIFORNIA                Dr Becky Miller 8621 West Third Street Suite
                          600E Los Angeles, CA 90048 Contact: Jean
                          Klein (310) 854-5841 OPEN 940520.
CALIFORNIA                Pacific Oaks Medical Group 150 N Robertson
                          Suite 300 Beverly Hills, CA 90211 Contact:
                          Rod Raphael (310) 652-2562 OPEN 940520.
CALIFORNIA                Pacific Oaks Medical Group 4940 Van Nuys Blvd
                          Sherman Oaks, CA 91403 Contact: Rod Raphael
                          (310) 652-2562 OPEN 940520.
CALIFORNIA                Tarzana Medical Center 16133 Ventura
                          Boulevard Suite 470 Encino, CA 91436 Contact:
                          Mary Hillner (818) 981-4156 OPEN 940520.
CALIFORNIA                Apogee Medical Group 3415 Sixth Avenue SW San
                          Diego, CA 92103 Contact: Steve Anderson (619)
                          295-4448 OPEN 940520.
CALIFORNIA                San Francisco General Hospital / UCSF 995
                          Potrero Avenue / Building 80 Ward 84 San
                          Francisco, CA 94110 Contact: Carol Arri (415)
                          476-9296 X 840OPEN 940520.
CALIFORNIA                Kaiser Permanente / HIV Research Unit 2590
                          Geary Boulevard San Francisco, CA 94115
                          Contact: Kate Fitzgerald (415) 202-3480 OPEN
                          940520.
CALIFORNIA                University of California/San Francisco 350
                          Parnassus Avenue Suite 701 San Francisco, CA
                          94117 Contact: Anita Harrison (415) 566-3431
                          OPEN 940520.
CALIFORNIA                VA San Francisco Hematology/Oncology Clinic
                          4150 Clement Street 111H1 San Francisco, CA
                          94121 Contact: Anita Harrison (415) 502-0873
                          OPEN 940520.
CALIFORNIA                Univrsity of California/San Francisco 400
                          Parnassus Avenue 5th Floor Room A502 San
                          Francisco, CA 94143-0324 Contact: Julie
                          Russel (415) 476-8911 OPEN 940520.
CALIFORNIA                East Bay AIDS Clinic 3031 Telegraph Avenue
                          Berkeley, CA 94705 Contact: Nancy Orcutt
                          (510) 204-1870 OPEN 940520.
DISTRICT OF COLUMBIA      Dr Mahmoud Mustafa 2311 M Street Suite 401
                          Washington, DC 20037 Contact: Cathi Carlise
                          (202) 331-3762 OPEN 940520.
FLORIDA                   University of Miami School of Medicine 1800
                          NW 10th Avenue 1st Floor Eliot Building
                          Miami, FL 33136 Contact: Janie Reese (305)
                          547-3840 OPEN 940520.
FLORIDA                   H Lee Moffit Cancer Center and Research
                          Institute 12902 Magnolia Drive Tampa, FL
                          33612 Contact: Jeane Richard (813) 972-8477
                          OPEN 940520.
GEORGIA                   American Medical Research Institute 1677
                          Tullie Circle Suite 118 Atlanta, GA 30329
                          Contact: Jane Green (404) 395-0009 OPEN
                          940520.
GEORGIA                   Infectious Disease Consortium Southeast
                          Clinical Resources 1758 Century Boulevard
                          Suite A Atlanta, GA 30345 Contact: Kim Prieto
                          (404) 388-3694 OPEN 940520.
ILLINOIS                  Northwestern Medical Faculty Foundation 233
                          East Erie Suite 700 Chicago, IL 60611
                          Contact: Rebecca Sunenshine (312) 908-2250
                          OPEN 940520.
ILLINOIS                  Rush Presbyterian Medical College 1725 W
                          Harrison Room 809 Chicago, IL 60612 Contact:
                          Jean Lydon (312) 942-5904 OPEN 940520.
ILLINOIS                  Illinois Masonic Medical Center The Cancer
                          Center 900 West Belmont Avenue Chicago, IL
                          60657 Contact: Helen Gereas (312) 296-7089
                          OPEN 940520.
MICHIGAN                  Henry Ford Medical Center Division of
                          Hematology/Oncology 2799 West Grand Boulevard
                          13th Floor Room 1305 Detroit, MI 48202
                          Contact: Carolyn Schmidt (313) 876-7277 OPEN
                          940520.
MISSOURI                  Washington University 660 South Euclid B8125
                          St Louis, MO 63108 Contact: Mary Gould (314)
                          454-0058 OPEN 940520.
NEW YORK                  St Vincent's Hospital and Medical Center 412
                          Sixth Avenue Suite 401 New York, NY 10011
                          Contact: Mary Catherine George (212) 228-4633
                          OPEN 940520.
NEW YORK                  New York University Medical Center 530 First
                          Avenue New York, NY 10016 Contact: Therese
                          Powers (212) 263-6485 OPEN 940520.
NEW YORK                  St Luke's-Roosevelt Hospital Center 126 West
                          60th Street New York, NY 10023 Contact: Diana
                          Mott-Tierno (212) 316-9689 OPEN 940520.
NEW YORK                  Roswell Park Cancer Institute Elm and Carlton
                          Street Buffalo, NY 14263 Contact: Paula
                          Grimes (716) 845-8965 OPEN 940520.
PENNSYLVANIA              The Tuttleman Center Graduate Hospital 1840
                          South Street 2nd floor Philadelphia, PA 19146
                          Contact: Barbara Rensman (215) 893-7541 OPEN
                          940520.
 
122
UNIQUE IDENTIFIER         FDA/00540
PROTOCOL ID NUMBERS       FDA 133A
PROTOCOL TITLE            Placebo-Controlled Trial of Safety and
                          Efficacy of Thalidomide in Patients With
                          Infections Due to Mycobacterium and/or HIV.
VERSION NUMBER & DATE     (930720)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To demonstrate, in patients with
                          tubercular or nontubercular mycobacterium
                          infections with or without HIV infection, the
                          safety of thalidomide use as judged by
                          symptoms, physical exam, and studies of
                          microbiologic, immunologic, hematologic,
                          renal, and hepatic status. To demonstrate
                          efficacy of the drug as judged by status of
                          fever, nutrition, tuberculosis lesions, and
                          immune responses. Methodology: Patients are
                          randomized to receive thalidomide or placebo
                          orally at 9 PM the night before beginning
                          anti-tuberculosis chemotherapy and continue
                          nightly for 7 nights. Patients are followed
                          for 28 days. Patients are stratified
                          according to HIV status and stage of HIV
                          infection.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive thalidomide or placebo orally at 9 PM
                          the night before beginning anti-tuberculosis
                          chemotherapy and continue nightly for 7
                          nights. Patients are followed for 28 days.
                          Patients are stratified according to HIV
                          status and stage of HIV infection.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (910401)
DISEASE STUDIED           Tuberculosis, Nontuberculous mycobacterial
                          infection, Mycobacterium avium-intracellul
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Positive AFB smear and/or
                          culture for Mycobacterium tuberculosis, M.
                          avium, or other mycobacterial infection, with
                          or without documented HIV infection. NOTE:
                          HIV positive patients must have CD4 count <
                          500 cells/mm3 and be on antiretroviral
                          therapy. 2. One of the following
                          manifestations: o Temperature over 38 C on at
                          least two occasions in the week prior to
                          study entry. o Recent weight loss of more
                          than 5 kilograms. o Pulmonary involvement of
                          one or more lobes or involvement of other
                          tissues due to tuberculosis or other
                          mycobacterial infections, or symptomatic
                          infections related to HIV status. o Night
                          sweats on two or more occasions in the week
                          prior to study entry. NOTE: Patients must be
                          hospitalized men aged 18-65 and
                          postmenopausal women to age 65. Anticipated
                          requirement for hospitalization must be at
                          least 10 days.
ELIGIBILITY               ARC. AIDS. OTHER.
OTHER PROTOCOL NUMBERS    None given
STUDY DESIGN              Randomized; Double-Blind; 2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 28 days.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Positive AFB smear and/or culture
                          for Mycobacterium tuberculosis, M. avium, or
                          other mycobacterial infection, with or
                          without documented HIV infection. NOTE: HIV
                          positive patients must have CD4 count < 500
                          cells/mm3 and be on antiretroviral therapy.
                          2. One of the following manifestations: o
                          Temperature over 38 C on at least two
                          occasions in the week prior to study entry. o
                          Recent weight loss of more than 5 kilograms.
                          o Pulmonary involvement of one or more lobes
                          or involvenment of other tissues due to
                          tuberculosis or other mycobacterial
                          infections, or symptomatic infections related
                          to HIV status. o Night sweats on two or more
                          occasions in the week prior to study entry.
                          NOTE: Patients must be hospitalized men aged
                          18-65 and postmenopausal women to age 65.
                          Anticipated requirement for hospitalization
                          must be at least 10 days. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
                          (HIV-positive patients must have CD4 count <
                          500 cells/mm3.) ( 0 - 100 - 200 - 300 - 400
                          ).
PATIENT AGE               AGE: 18 Years - 65 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Postmenopausal or
                          permanent sterility including hysterectomy or
                          bilateral tubal ligation.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required for
                          HIV-positive patients if CD4 count < 500
                          cells/mm3: Antiretroviral therapy.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 66 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Future reproduction.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded:
                          Neuropathy or other disorders with risk of
                          neuropathy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0184  Thalidomide
MANUFACTURERS             Drug 1: Gruenthal GMBH Steinfeldstrase Number
                          2 Stolberg, GE 5190 Contact: Unspecified.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Administered at 9 PM
                          the night before beginning anti-tuberculosis
                          chemotherapy and continuing nightly for 7 ni
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 14 days if TB only; 21
                          days if HIV positive and TB.
SUPPORTING AGENCY         Rockefeller University.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS/DRUG
                          THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS/DRUG THERAPY
MESH HEADING              Adult
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium Infections/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Mycobacterium Infections, Atypical/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Mycobacterium tuberculosis/*DRUG EFFECTS
MESH HEADING              Opportunistic Infections/COMPLICATIONS/*DRUG
                          THERAPY
MESH HEADING              Thalidomide/*ADVERSE EFFECTS/THERAPEUTIC USE
CAS REGISTRY NUMBER       50-35-1 (Thalidomide)
LAST REVISION DATE        910401
ENTRY MONTH               9307
NEW YORK                  Bellevue Hospital Center 27th Street and 1st
                          Avenue / Room 7N24 New York, NY 10016
                          Contact: William Rom (212) 263-6479 Contact:
                          (212) 263-7098 OPEN 910401.
NEW YORK                  Rockefeller University 1230 York Avenue / Box
                          280 New York, NY 10021-6399 Contact: Margaret
                          Burroughs (212) 327-7177 OPEN 910401.
 
123
UNIQUE IDENTIFIER         FDA/00535
PROTOCOL ID NUMBERS       FDA 131A
PROTOCOL TITLE            Phase I Study to Evaluate the Safety and
                          Tolerance of RMP-7 Administered With
                          Amphotericin B to Patients With HIV Infection
                          and Cryptococcal Meningitis.
VERSION NUMBER & DATE     (930607)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of escalating
                          doses of RMP-7 administered in persons with
                          HIV infection and cryptococcal meningitis and
                          to determine the MTD of the drug. To evaluate
                          the pharmacokinetics, including cerebrospinal
                          fluid (CSF) penetration, of amphotericin B
                          when administered with RMP-7. Methodology:
                          Patients receive intravenous RMP-7 added to
                          conventional therapy with intravenous
                          amphotericin B (with or without flucytosine).
                          Treatment continues for 14 days, with
                          follow-up visits 4 and 12 weeks later.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravenous
                          RMP-7 added to conventional therapy with
                          intravenous amphotericin B (with or without
                          flucytosine). Treatment continues for 14
                          days, with follow-up visits 4 and 12 weeks
                          later.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (931105)
DISEASE STUDIED           Cryptococcal meningitis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection by
                          ELISA confirmed by Western blot. 2. Acute
                          cryptococcal meningitis defined by positive
                          cryptococcal culture from CSF or detection of
                          cryptococcal antigen in CSF. Patients with a
                          first recrudescence are permitted if no
                          abscess is evident on MRI or CT and
                          intracranial pressure is not substantially
                          elevated based on ocular findings and opening
                          pressure during lumbar puncture.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    ALK01-006
STUDY DESIGN              Randomized; Double-Blind; Dose Escalating;
                          Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Maximum tolerated dose (MTD),
                          Drug safety, Pharmacokinetics, Combination
                          drug therapy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 14 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 11 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Acute cryptococcal
                          meningitis. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7.0 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 7.5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 7.5 x ULN.
                          Neutrophils >= 750 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Up to 1 mg/kg
                          amphotericin B for the current episode of
                          cryptococcal meningitis.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of any bleeding disorder. 2. History
                          of active renal or hepatic disease. 3.
                          Myocardial infarction within the previous 3
                          months. 4. Stroke within the previous 3
                          months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Cardiovascular disorders including congestive
                          heart failure, uncontrolled hypertension
                          (seated diastolic blood pressure > 95 mm Hg),
                          or symptomatic ischemic heart disease
                          (angina). 2. Orthostatic hypotension, defined
                          as a decrease in systolic blood pressure of
                          >= 20 mm Hg upon standing. 3. Coma. 4. Other
                          CNS disease (e.g., other intracranial
                          infections) that may interfere with
                          assessment of response. 5. Opening CSF
                          pressure >= 350 mm or papilledema. (For
                          patients with recurrent disease, evidence of
                          mass effect on either MRI or CT excludes.) 6.
                          Any concurrent disease that would preclude
                          participation in the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0182  RMP-7
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0006  Amphotericin B
TRADE NAME OF SUBSTANCE   Drug 2 Fungizone
MANUFACTURERS             Drug 1: Alkermes Incorporated 64 Sidney
                          Street Cambridge, MA 02139 Contact: Dr
                          William F Graney (617) 494-0171.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company PO Box
                          4000 Princeton, NJ 08534-4000 Contact: Dr Joe
                          Sonk (609) 252-5710.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous. Drug 2:
                          Intravenous
OTHER TREATMENT INFO.     TREATMENT DURATION: 14 days.
SUPPORTING AGENCY         Alkermes Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Amphotericin B/ADVERSE EFFECTS/
                          *PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Antifungal Agents/*ADMINISTRATION & DOSAGE/
                          ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Meningitis/*DRUG THERAPY/ETIOLOGY
MESH HEADING              Middle Age
MESH HEADING              Opportunistic Infections/COMPLICATIONS/*DRUG
                          THERAPY
CAS REGISTRY NUMBER       0 (Antifungal Agents)
CAS REGISTRY NUMBER       1397-89-3 (Amphotericin B)
LAST REVISION DATE        931105
ENTRY MONTH               9307
CALIFORNIA                Los Angeles County / USC Medical Center 1129
                          North State Street / Room 2E10 Pediatric
                          Pavilion Los Angeles, CA 90033 Contact: DeAnn
                          Diamond (213) 226-3695 CLOSED 940301.
CALIFORNIA                University of California / San Diego
                          Treatment Center 2760 5th Avenue / Suite 300
                          San Diego, CA 92103 Contact: Alanna Fraser
                          (619) 543-8080 OPEN 930301.
CALIFORNIA                UCI Medical Center 101 City Drive South /
                          Building 53 / Route 81 Orange, CA 92668
                          Contact: Sheila Fitzgibbons (714) 456-7612
                          OPEN 930301.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 931105.
NORTH CAROLINA            Bowman Gray School of Medicine Medical Center
                          Boulevard Winston-Salem, NC 27157-1042
                          Contact: Ronald Washburn (910) 716-4218 OPEN
                          930301.
NORTH CAROLINA            Duke University Medical Center / Infectious
                          Diseases Clinic Trent Drive/ Room 0201 /
                          South Hospital / Orange Zone Durham, NC 27710
                          Contact: Laura Stewart (919) 684-8216 OPEN
                          930301.
NORTH CAROLINA            East Carolina University School of Medicine
                          Section of Infect Diseases Greenville, NC
                          27858-4354 Contact: Jean Askew (919) 816-2578
                          CLOSED 940610.
NEW YORK                  SUNY at Stony Brook Health Sciences Center /
                          Div Infect Dis HSC T 15 Room 080 Stony Brook,
                          NY 11794-8153 Contact: Ruth Ann Burk (516)
                          444-1658 OPEN 930301.
OHIO                      Case Western Reserve University 10900 Euclid
                          Avenue Cleveland, OH 44106 Contact: Corrine
                          Connor (216) 844-3287 OPEN 940215.
PENNSYLVANIA              Pennsylvania State University / Hershey
                          Medical Center 500 Univ Drive / PO Box 850 /
                          Biomedical Rsrch Bldg C-6833 Hershey, PA
                          17033 Contact: Francine Damianos (717)
                          531-7488 OPEN 930301.
 
124
UNIQUE IDENTIFIER         FDA/00575
PROTOCOL ID NUMBERS       FDA 129D
PROTOCOL TITLE            3TC (Lamivudine; GR109714X) Open-Label
                          Program.
VERSION NUMBER & DATE     (931104)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Child
GENERAL DESCRIPTION       PURPOSE: To make lamivudine (3TC) available
                          to patients with progressive, symptomatic HIV
                          disease who cannot participate in a
                          controlled clinical trial and who are
                          refractory or unable to tolerate other
                          therapies. To collect data pertaining to the
                          safety of 3TC at two dose levels: 4 and 8
                          mg/kg/day. To evaluate the effect of 3TC on
                          markers of hepatitis B in co-infected
                          patients at five to ten selected sites.
                          Methodology: Patients are randomized to
                          receive one of two doses of 3TC for a
                          duration determined by the patient's
                          physician or until termination of the
                          program. Patients are followed monthly. For
                          selected sites only, serum samples are
                          collected every 3 months from patients
                          identified as HBsAg positive.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive one of two doses of 3TC for a
                          duration determined by the patient's
                          physician or until termination of the
                          program. Patients are followed monthly. For
                          selected sites only, serum samples are
                          collected every 3 months from patients
                          identified as HBsAg positive.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940511)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Progressive, symptomatic HIV
                          disease. 2. Mean CD4 count <= 300 cells/mm3
                          (two samples collected at least 30 days
                          apart, but within 90 days of enrollment). 3.
                          Unable to participate in a controlled trial.
                          4. Refractory to or unable to tolerate other
                          therapies.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    NUCA 3004
STUDY DESIGN              Open Label; Randomized; Dose Comparison
PROTOCOL DETAILS          STUDY INTENT: Expanded access, Drug safety,
                          Drug efficacy.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Determined by
                          patient's physician or until study
                          termination.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must: 1.
                          Have progressive, symptomatic HIV disease. 2.
                          Have a mean CD4 count <= 300 cells/mm3. 3. Be
                          unable to participate in a controlled trial.
                          4. Be refractory to or unable to tolerate
                          other therapies. 5. Be able to attend clinic
                          on a monthly schedule. 6. Have consent of
                          parent or guardian if under the age of
                          consent. NOTE: If a pregnant or
                          breast-feeding woman requests enrollment, her
                          physician should contact Glaxo staff directly
                          to discuss the case. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 300 cells/mm3. ( 0 -
                          100 - 200 - 300 ).
PATIENT AGE               AGE: 03 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Practice of unsafe sex.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Patients located in countries
                          other than the United States or Canada are
                          not eligible.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0126  Lamivudine
TRADE NAME OF SUBSTANCE   Drug 1 3TC
MANUFACTURERS             Drug 1: Glaxo Incorporated 5 Moore Drive
                          Research Triangle Park, NC 27709 Contact:
                          Jennifer McMillan (919) 248-2100.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 4 or 8 mg/kg/day
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 4 or 8 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral; 300 mg tablets
                          (adults) or 10 mg/ml syrup (children)
OTHER TREATMENT INFO.     TREATMENT DURATION: Duration determined by
                          patient's physician or until study
                          termination.
SUPPORTING AGENCY         Glaxo Incorporated.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Reverse Transcriptase/ANTAGONISTS & INHIB
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       EC 2
LAST REVISION DATE        940511
ENTRY MONTH               9312
NEW JERSEY                Kern - McNeill International 159 South Street
                          Morristown, NJ 07960 Contact: Michele McNeill
                          (800) 248-9757 OPEN / USA Accrual 931029.
 
125
UNIQUE IDENTIFIER         FDA/00522
PROTOCOL ID NUMBERS       FDA 126A
PROTOCOL TITLE            Phase I/II Study of the Tolerance and
                          Efficacy of Combined Use of Didanosine
                          (2',3'-Dideoxyinosine; ddI) and Lentinan in
                          HIV-Positive Patients.
VERSION NUMBER & DATE     (930511)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
PROTOCOL CHAIRS           CHAIR  Lang W
PROTOCOL CHAIRS           CO-CHAIR  Goodgame J
GENERAL DESCRIPTION       PURPOSE: To determine the tolerance and side
                          effects of a combination of lentinan and
                          didanosine (ddI) compared with ddI alone. To
                          determine whether the combination of lentinan
                          and ddI produces a significant
                          immunorestorative effect within the study
                          observation period (6-12 months) as measured
                          by an increase in one or more of the
                          following: neutrophil count and activity,
                          T-cell subsets, and a decrease in p24
                          antigen. Methodology: Patients are randomized
                          to receive either lentinan (40 patients) or
                          placebo (10 patients) in combination with ddI
                          for at least 26 weeks; those tolerating their
                          dose may be offered continuation of therapy
                          for an additional 26 weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either lentinan (40 patients) or
                          placebo (10 patients) in combination with ddI
                          for at least 26 weeks; those tolerating their
                          dose may be offered continuation of therapy
                          for an additional 26 weeks.
PROTOCOL PHASE            Phase I / Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920219)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositivity. 2.
                          Absolute CD4 count of 200 - 500 cells/mm3. 3.
                          No active opportunistic infection or Kaposi's
                          sarcoma.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    91-10-15
STUDY DESIGN              Randomized; 2-Arm; Drug Combination; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug tolerance, Drug efficacy,
                          Combination and single drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 50 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 26-52 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV seropositivity. 2. Absolute CD4
                          count of 200 - 500 cells/mm3. 3. No active
                          opportunistic infection or Kaposi's sarcoma.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 30 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 10 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 500 cells/mm3. (
                          200 - 300 - 400 - 500 ).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 4 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 4 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: > 60.
PATIENT AGE               AGE: 18 Years - 60 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or agree to use
                          barrier methods of birth control /
                          contraception during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior ddI for no
                          longer than 3 months.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years. 61 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use barrier methods of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active drug abuse.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded: Radiotherapy
                          within 1 month prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT TREATMENT: Excluded: Radiotherapy.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 1 month
                          prior to study entry: 1. Antiretroviral
                          agents other than ddI (patients may have
                          received prior ddI for no longer than 3
                          months total). 2. Steroids. 3. Cytotoxic
                          agents. 4. Immunosuppressive agents. 5.
                          Immunomodulators.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antiretroviral agents other than ddI. 2.
                          Steroids. 3. Cytotoxic agents. 4.
                          Immunosuppressive agents. 5.
                          Immunomodulators. 6. 1-Thyroxine.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Lymphoid malignancy. 2. Pancreatitis. 3.
                          Peripheral neuropathy. 4. Critical illness.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Must not be currently
                          hospitalized.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0171  Lentinan
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0016  Didanosine
TRADE NAME OF SUBSTANCE   Drug 2 Videx
MANUFACTURERS             Drug 1: AJI PHARMA USA Inc 500 Frank Burr
                          Boulevard Teaneck, NJ 07666 Contact: Dr
                          Maxwell Gordon (201) 836-1196 Contact: Mario
                          Guralnik (201) 836-1196.
MANUFACTURERS             Drug 2: Bristol-Myers Squibb Company 2400
                          West Lloyd Expressway Evansville, IN
                          47721-0001 Contact: DDI Information (800)
                          662-7999.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 2 mg (or placebo)
                          weekly for 26 weeks (possibly extendefor an
                          additional 26 weeks). Drug 2: 400 mg BID
                          daily for 26 weeks (possibly extended for
                          anadditional 26 weeks)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 2: 800 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous. Drug 2:
                          Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 26 weeks.
OTHER TREATMENT INFO.     END POINT: Toxicity, drug efficacy.
SUPPORTING AGENCY         AJI PHARMA USA Inc.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Didanosine/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Lentinan/*ADVERSE EFFECTS/THERAPEUTIC USE
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       37339-90-5 (Lentinan)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
LAST REVISION DATE        920219
ENTRY MONTH               9305
CALIFORNIA                ViRx Inc 1375 Sutter Street Suite 407 San
                          Francisco, CA 94102 Contact: Karen Allman
                          (415) 474-4440 OPEN 930511.
FLORIDA                   Dr Goodgame and Hopkins 340 N Maitland Avenue
                          Maitland, FL 32751 Contact: Chuck DeMarzo
                          (407) 647-6000 OPEN 930511.
 
126
UNIQUE IDENTIFIER         FDA/00479
PROTOCOL ID NUMBERS       FDA 121A
PROTOCOL TITLE            A Randomized Phase III Clinical Trial of
                          Daunoxome Versus Combination Chemotherapy
                          With Adriamycin/Bleomycin/Vincristine (ABV)
                          in the Treatment of HIV-Associated Kaposi's
                          Sarcoma.
VERSION NUMBER & DATE     (920514)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To compare the toxicity profiles
                          (severity and time to onset from initiation
                          of therapy) between daunorubicin (liposomal)
                          and combination chemotherapy with
                          doxorubicin/bleomycin/vincristine (ABV), with
                          both regimens administered in combination
                          with antiretroviral therapy. To compare the
                          duration of responses, response rates, and
                          times to response.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940510)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Serological documentation of
                          HIV infection by ELISA and Western blot. 2.
                          Biopsy-proven Kaposi's sarcoma with advanced
                          disease defined by any of the following:
                          presence of 25 or more mucocutaneous lesions;
                          development of 10 or more lesions within 1
                          month; presence of confluent or symptomatic
                          mucocutaneous involvement in the event of
                          fewer than 25 lesions; symptomatic visceral
                          involvement; or lymphedema.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    103-09
STUDY DESIGN              Randomized
PROTOCOL DETAILS          STUDY INTENT: Comparative drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 13 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Advanced Kaposi's
                          sarcoma. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 1.5 x ULN g/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1500 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.5 x ULN mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50.
PATIENT INCLUSION CRIT.   OTHER: Cardiac left ventricular ejection
                          fraction >= 45 percent.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior
                          intralesional vinblastine.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Symptomatic AIDS-defining opportunistic
                          infection within 2 weeks of entry. 2. History
                          of malignancy other than Kaposi's sarcoma,
                          basal cell carcinoma, or carcinoma in situ of
                          the cervix. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR TREATMENT: Excluded within 7 days prior
                          to study entry: 1. Radiation. 2. Local
                          therapies (e.g., cryotherapy).
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior systemic
                          chemotherapy. 2. Intralesional therapies
                          within 7 days prior to study entry. 3. Growth
                          factors (G-CSF or GM-CSF), immune modifiers,
                          or investigational agents within 14 days
                          prior to study entry. 4. Interferon
                          preparations (alpha or beta) within 28 days
                          prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Concurrent
                          ganciclovir.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Acute intercurrent infection other than
                          genital herpes. 2. Uncompensated
                          cardiovascular, hepatic, renal, or pulmonary
                          disease unrelated to Kaposi's sarcoma. 3.
                          Symptomatic peripheral neuropathy. 4. Any
                          condition that compromises ability to give
                          informed consent or complete the study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0155  Daunorubicin (liposomal)
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0047  Doxorubicin
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0045  Bleomycin
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0046  Vincristine
TRADE NAME OF SUBSTANCE   Drug 1 Daunoxome
TRADE NAME OF SUBSTANCE   Drug 2 Adriamycin
TRADE NAME OF SUBSTANCE   Drug 3 Blenoxane
TRADE NAME OF SUBSTANCE   Drug 4 Oncovin
MANUFACTURERS             Drug 1: Vestar Inc 650 Cliffside Drive San
                          Dimas, CA 91773 Contact: Jeanni Brenning
                          (909) 394-4110.
MANUFACTURERS             Drug 2: Adria Laboratories Incorporated PO
                          Box 16529 Columbus, OH 43216-6529 Contact: Dr
                          Sunil Gupta (614) 764-8178.
MANUFACTURERS             Drug 3: Bristol-Myers Squibb Company 345 Park
                          Avenue New York, NY 10154 Contact: Nancy
                          Goldfarb (212) 546-5107.
MANUFACTURERS             Drug 4: Eli Lilly and Company 307 East
                          McCarty Street Indianapolis, IN 46285
                          Contact: Medical Department (800) 545-5979.
SUPPORTING AGENCY         Vestar Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Bleomycins/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Daunorubicin/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Doxorubicin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Drug Carriers
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Liposomes
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Vincristine/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       0 (Bleomycins)
CAS REGISTRY NUMBER       0 (Drug Carriers)
CAS REGISTRY NUMBER       0 (Liposomes)
CAS REGISTRY NUMBER       20830-81-3 (Daunorubicin)
CAS REGISTRY NUMBER       23214-92-8 (Doxorubicin)
CAS REGISTRY NUMBER       57-22-7 (Vincristine)
LAST REVISION DATE        940510
ENTRY MONTH               9212
ARIZONA                   University of Arizona / Arizona Cancer Center
                          1501 N Campbell Avenue Tucson, AZ 85724
                          Contact: Dr G Gonzalez (602) 626-6372 OPEN
                          921120.
CALIFORNIA                Kenneth Norris Jr Cancer Hospital 1441
                          Eastlake Avenue / Room 162 Los Angeles, CA
                          90033 Contact: Dr Parkish Gill (213) 342-2448
                          OPEN 921120.
CALIFORNIA                The Desert Hospital Comprehensive Cancer
                          Center 1695 N Sunrise Way Palm Springs, CA
                          92262 Contact: Dr Sanford Kempin (619)
                          323-6891 OPEN 921120.
CALIFORNIA                Saint Francis Memorial Hospital 900 Hyde
                          Street San Francisco, CA 94109 Contact: Dr
                          Gifford Leoung (415) 353-6216 OPEN 921120.
CALIFORNIA                Institute for HIV Research / Davies Med Ctr
                          Castro and Dubose Streets San Francisco, CA
                          94114 Contact: Dr Ivan Silverberg (415)
                          861-7530 OPEN 921120.
COLORADO                  Denver General Hospital / Div of Medical
                          Oncology Box 0146 / 777 Bannock Street
                          Denver, CO 80204-4507 Contact: Dr Adam Myers
                          (303) 436-5774 OPEN 931105.
DISTRICT OF COLUMBIA      George Washington U Med Ctr / Div of
                          Hematology/Oncology 2150 Pennsylvania Avenue
                          NW Washington, DC 20037 Contact: Dr Philip
                          Cohen (202) 994-7716 OPEN 921120.
FLORIDA                   Univ of Miami School of Med / Comprehensive
                          AIDS Program Div of Gen Med R-60A / 1800 NW
                          10th Avenue Miami, FL 33101 Contact: Margaret
                          A Fischl (305) 547-3847 OPEN 931105.
ILLINOIS                  Northwestern University Medical School 233
                          East Erie Street / Suite 700 Chicago, IL
                          60611 Contact: Dr J Hayden von Roenn (312)
                          908-9412 OPEN 921120.
MASSACHUSETTS             New England Deaconess Hospital / Dept of
                          Hemat/Oncol 110 Frances Street / 4A Boston,
                          MA 02215 Contact: Dr David Scadden (617)
                          732-8540 OPEN 921120.
NEW YORK                  New York U Med Ctr / Dept of Medicine / Div
                          of Oncology 550 1st Avenue New York, NY 10016
                          Contact: Dr James Wernz (212) 263-7227 OPEN
                          921120.
OREGON                    Northwest Kaiser Permanente Med Ctr / Dept of
                          Hemat/Oncol 3414 N Kaiser Center Drive
                          Portland, OR 97227 Contact: Michael Allison
                          (503) 249-3313 Contact: Dr Mark Rarick (503)
                          249-3430 OPEN 921120.
 
127
UNIQUE IDENTIFIER         FDA/00644
PROTOCOL ID NUMBERS       FDA 120
PROTOCOL TITLE            An Open Multicenter Trial of Fluconazole Oral
                          Suspension in the Treatment of Esophageal
                          Candidiasis in Immunocompromised Patients.
VERSION NUMBER & DATE     (940727)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To determine the safety, toleration,
                          and efficacy of fluconazole oral suspension
                          in the treatment of esophageal candidiasis in
                          immunocompromised patients, including those
                          with AIDS. Methodology: Patients receive
                          fluconazole oral suspension for a minimum of
                          3 weeks and maximum of 8 weeks. Patients are
                          evaluated weekly, and treatment continues for
                          2 weeks after resolution of symptoms.
                          Endoscopic exams and possibly biopsies are
                          performed at baseline and at the end of
                          treatment. Patients undergo follow-up at 2
                          weeks post-treatment.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive fluconazole
                          oral suspension for a minimum of 3 weeks and
                          maximum of 8 weeks. Patients are evaluated
                          weekly, and treatment continues for 2 weeks
                          after resolution of symptoms. Endoscopic
                          exams and possibly biopsies are performed at
                          baseline and at the end of treatment.
                          Patients undergo follow-up at 2 weeks
                          post-treatment.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920121)
DISEASE STUDIED           Candidiasis, esophageal.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS or other
                          immunocompromising condition (e.g.,
                          malignancy, renal transplant). 2. Clinical
                          diagnosis of candidal esophagitis based on
                          symptoms such as dysphagia, odynophagia, or
                          retrosternal pain.
ELIGIBILITY               AIDS. OTHER - immunocompromised.
OTHER PROTOCOL NUMBERS    R-0220
STUDY DESIGN              Open Label; Multicenter; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Up to 10 weeks
                          (including follow-up 2 weeks post-treatment).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS or other immunocompromising
                          condition. 2. Candidal esophagitis. 3. Life
                          expectancy of at least 2 months. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3 mg/dl. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 3 x ULN.
                          Prothrombin time <= 5 sec over control
                          (unless correctable by vitamin K).
PATIENT AGE               AGE: 13 Years - 70 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of allergy to imidazoles or azoles.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years. 71 Years - 99 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Active use of illicit or
                          illegal drugs.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Any oral or
                          topical antifungal therapy within the past 3
                          days.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Concomitant oral or topical antifungal agent.
                          2. Other experimental medications.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Evidence of non-candidal systemic fungal
                          infection. 2. Abnormalities that may preclude
                          esophagoscopy or endoscopy. 3. Unable to
                          tolerate fluconazole. 4. Unable to give
                          informed consent. 5. Enrollment in other
                          experimental trials of approved or
                          non-approved drugs or systemic compounds
                          (unless approved by the Pfizer Clinical
                          Monitor). 6. Other condition that would make
                          patient unsuitable for enrollment.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0005  Fluconazole
TRADE NAME OF SUBSTANCE   Drug 1 Diflucan
MANUFACTURERS             Drug 1: Pfizer Incorporated / Roerig Division
                          235 East 42nd Street New York, NY 10017-7851
                          Contact: Professional Information (212)
                          573-2187.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Administered for 3 -
                          8 weeks
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, suspension
OTHER TREATMENT INFO.     TREATMENT DURATION: 3 - 8 weeks.
SUPPORTING AGENCY         Pfizer Incorporated / Roerig Division.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Candidiasis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Esophagitis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Fluconazole/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Immunocompromised Host
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        920121
ENTRY MONTH               9408
CALIFORNIA                Los Angeles - USC Medical Center / GI and
                          Liver Disease 1200 North State Street / Room
                          12-137 Los Angeles, CA 90033 Contact:
                          Francisco Garcia (213) 226-6939 Contact: Dr
                          Loren Laine (213) 226-7994 Contact: (213)
                          226-7995 OPEN 940808.
 
128
UNIQUE IDENTIFIER         FDA/00477
PROTOCOL ID NUMBERS       FDA 119A
PROTOCOL TITLE            A Study to Evaluate the Effect of Cimetidine
                          on CD4 Lymphocyte Counts in HIV Infection.
VERSION NUMBER & DATE     (920403)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To determine the change in CD4 count
                          after 4 and 8 weeks in HIV-infected patients
                          treated with cimetidine compared to placebo.
                          To observe time-associated trends at weeks 4,
                          8, 12, and 16 in the change of CD4 counts for
                          patients taking cimetidine for the full 16
                          weeks. To establish a safety record for
                          cimetidine use in HIV-positive patients.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920501)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: HIV positive by antibody testing
                          (including tests performed at anonymous test
                          sites) or presumptive diagnosis of HIV
                          positive status by symptoms and lab data
                          (diagnosis of ARC or AIDS not required,
                          provided other criteria are met).
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    92-01
STUDY DESIGN              Placebo-Controlled
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: HIV positivity. NOTE: Patients on an
                          antiviral or immunomodulating drug must have
                          received it for at least 2 months and have no
                          intention to make clinical or therapeutic
                          changes in the first 8 weeks (such as adding
                          a new agent or discontinuing effective viral
                          suppressive therapy) that may interfere with
                          the study. NOTE: Patients who become pregnant
                          after enrollment will be permitted to
                          continue on study drug but must sign an
                          additional informed consent indicating their
                          awareness of the issues in taking a drug with
                          limited safety data during pregnancy. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 750 cells/mm3. Alkaline
                          phosphatase < 5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Antiviral and
                          immunomodulating drugs, provided patient has
                          been on such therapy for at least 2 months
                          prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. All
                          FDA-approved medications, antiretrovirals,
                          and PCP prophylaxis drugs, with the exception
                          of warfarin (Coumadin). 2. Other
                          self-prescribed medications available either
                          over the counter or through buyer's clubs.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: cimetidine (Tagamet),
                          ranitidine (Zantac), famotidine (Pepcid), and
                          nazitidine (Azid).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Warfarin
                          (Coumadin).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          intolerance or hypersensitivity to
                          cimetidine. 2. Evidence of active
                          opportunistic infection or malignancy
                          requiring high-dose systemic chemotherapy. 3.
                          Any symptoms suggestive of concurrent illness
                          that are not attributable to overall
                          impairment by HIV or are not diagnosable
                          based on the available evidence. 4. Inability
                          to swallow tablets (gastric feeding tubes are
                          allowed. 5. Not willing to comply with visit
                          schedule and study procedures.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0150  Cimetidine
TRADE NAME OF SUBSTANCE   Drug 1 Tagamet
MANUFACTURERS             Drug 1: Smith Kline Beecham 1 Franklin Plaza
                          / PO Box 7929 Philadelphia, PA 19101-7929
                          Contact: Product Information / Med Dept (800)
                          366-8900 X 5231.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, tablets
SUPPORTING AGENCY         Community Research Initiative of New England.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cimetidine/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       51481-61-9 (Cimetidine)
LAST REVISION DATE        920501
ENTRY MONTH               9212
MASSACHUSETTS             Community Research Initiative of New England
                          320 Washington Street / 3rd Floor Brookline,
                          MA 02146 Contact: Jeanne Day (617) 566-4004
                          OPEN 921124.
 
129
UNIQUE IDENTIFIER         FDA/00433
PROTOCOL ID NUMBERS       FDA 104B
PROTOCOL TITLE            A Comparative Trial of 256U87 and Acyclovir
                          for the Suppression of Anogenital Herpes
                          Infections in HIV-Infected Patients.
VERSION NUMBER & DATE     (911210)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To determine the safety and efficacy
                          of oral 256U87 compared to acyclovir in the
                          treatment of recurrent anogenital herpes in
                          HIV-infected patients with CD4 counts = or >
                          100 cells/mm3.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940502)
DISEASE STUDIED           Herpes simplex, anogenital.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection with CD4 count =
                          or > 100 cells/mm3. 2. History of recurrent
                          anogenital herpes simplex virus (HSV). 3.
                          Documented culture for anogenital HSV within
                          the last 5 years. 4. Recurrence of anogenital
                          HSV (with or without culture) within 1 year
                          prior to study entry.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    07
STUDY DESIGN              Drug Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Comparative drug therapy.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 713 (940502).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 46 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection with CD4 counts = or >
                          100 cells/mm3. 2. Documented culture of
                          anogenital herpes simplex virus (HSV) within
                          the last 5 years. 3. History of recurrent
                          anogenital HSV infection, with a recurrence
                          (with or without culture) within 1 year prior
                          to study. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: >= 100 cells/mm3. ( 100
                          - 200 - 300 - 400 - 500 - 600 - 700 - 800
                          plus).
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 35 ml/min.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hypersensitivity to acyclovir.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Systemic
                          antiherpes medication. 2. Interferon.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded:
                          Malabsorption or vomiting that would
                          potentially limit the retention and
                          absorption of oral therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0119  Valaciclovir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0008  Acyclovir
TRADE NAME OF SUBSTANCE   Drug 2 Zovirax
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUPPORTING AGENCY         Burroughs Wellcome Company.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Acyclovir/*THERAPEUTIC USE
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*THERAPEUTIC USE
MESH HEADING              Anus Diseases/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Herpes Genitalis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       59277-89-3 (Acyclovir)
LAST REVISION DATE        940502
ENTRY MONTH               9207
ALABAMA                   University of South Alabama Division of
                          Infectious Disease Mobile, AL 36688 Contact:
                          Dr Halim (205) 479-6933 Contact: Judy Miller
                          (205) 479-6933 OPEN 920729.
ARIZONA                   University of Arizona / Section of Infectious
                          Diseases 1501 North Campbell Avenue Tucson,
                          AZ 85724 Contact: Joel Gray (602) 626-2533
                          OPEN 920729.
CALIFORNIA                Combat Group 1800 North Highland Suite 610
                          Los Angeles, CA 90028 Contact: Holly Boyd
                          (213) 469-5888 OPEN 940502.
CALIFORNIA                USC Medical Center 1175 North Cummings Street
                          / Room 349 Los Angeles, CA 90033 Contact:
                          Irene Teran (213) 343-8288 OPEN 931110.
CALIFORNIA                UCSD Medical Center 8208 225 Dickinson Street
                          San Diego, CA 92103 Contact: Kathy Nuffer
                          (619) 543-8080 OPEN 920729.
CALIFORNIA                US Naval Hospital Florida Canyon Drive San
                          Diego, CA 92134-5000 Contact: Elaine
                          Schreiber (619) 532-6131 OPEN 931110.
CALIFORNIA                UCI Medical Center 101 City Drive South /
                          Building 53 / Route 81 Orange, CA 92668
                          Contact: Sheila Fitzgibbons (714) 456-7612
                          OPEN 920729.
CALIFORNIA                ViRx Incorporated 1375 Sutter Street / Suite
                          407 San Francisco, CA 94109 Contact: Joyce
                          Amann (415) 474-4440 Contact: Michael Baker
                          (415) 474-4440 OPEN 920729.
CALIFORNIA                San Francisco General Hospital 995 Portrero
                          Avenue Bldg 80 Ward 84 San Francisco, CA
                          94110 Contact: Patricia Duff (415) 431-0790
                          OPEN 920729.
CALIFORNIA                Marcus Conant M D 1635 Divisadero Street
                          Suite 600 San Francisco, CA 94115 Contact:
                          Steven Ellis (415) 923-0222 OPEN 920729.
CALIFORNIA                Infectious Disease Medical Gp / Adult
                          Immunology Clinic 3012 Summit Street Sixth
                          Floor Oakland, CA 94609 Contact: Jamie
                          Carroll (510) 420-6014 Contact: Doctors
                          office (510) 834-2800 OPEN 920729.
CONNECTICUT               HIV Care Program / Veterans Administration
                          Medical Ctr 111-1 950 Campbell Avenue West
                          Haven, CT 06516 Contact: Elizabeth Cooney
                          (203) 932-5711 X 374CLOSED 940502.
DISTRICT OF COLUMBIA      Georgetown University Medical Center Suite
                          110 Kober-Cogan Bldg / 3800 Reservoir Road NW
                          Washington, DC 20007 Contact: Catherine
                          O'Leary (202) 687-5378 OPEN 920729.
DISTRICT OF COLUMBIA      Whitman Walker Clinic 1701 NW 14th Street
                          Washington, DC 20009 Contact: Christiane
                          Jones (202) 745-6151 OPEN 940502.
DISTRICT OF COLUMBIA      George Washington University Medical Center
                          2300 I Street NW / Number 202 Washington, DC
                          20037 Contact: Barbara Lewis (202) 994-2417
                          OPEN 931110.
DISTRICT OF COLUMBIA      Washington Regional AIDS Program 50 Irving
                          Street / NW Washington, DC 20422 Contact:
                          Donna Mills (202) 745-8695 OPEN 931110.
FLORIDA                   University of South Florida / Div of Infect
                          and Tropical Dis 5471 4th Street South St
                          Petersburg, FL 33705 Contact: Pat Seeley
                          (813) 974-3163 OPEN 920729.
GEORGIA                   Emory Medical School / Division of Infectious
                          Diseases 69 Butler Street Atlanta, GA 30303
                          Contact: Kara Barrett (404) 616-2440 OPEN
                          920729.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          deLeon Avenue / Suite 130 Atlanta, GA 30308
                          Contact: Betty Mear (404) 876-2317 OPEN
                          931110.
IOWA                      University of Iowa / Div of Infectious
                          Disease 200 Hawkins Road / SW54 / GH Iowa
                          City, IA 52242 Contact: Julie Katseres (319)
                          353-8441 OPEN 931110.
ILLINOIS                  Northwestern Memorial Hospital / Section of
                          Infect Disease 250 East Superior Street
                          Chicago, IL 60611 Contact: Patty Nedved (312)
                          908-7631 OPEN 920729.
ILLINOIS                  Rush Presbyterian - St Lukes Medical Ctr /
                          Sec of Infect Dis 1725 West Harrison Ave
                          Suite 143 Academic Facility Chicago, IL 60612
                          Contact: Donna Samano (312) 942-5865 OPEN
                          920729.
INDIANA                   Indiana University Medical School / Division
                          of Infect Dis Emerson Hall Room 435 / 545
                          Barnhill Drive Indianapolis, IN 46223
                          Contact: Beth Zwicki (317) 274-8456 Contact:
                          Heather Nixon (317) 274-8456 OPEN 920729.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 920729.
MARYLAND                  University of Maryland 22 South Greene Street
                          P O Box 243 Baltimore, MD 21201 Contact:
                          Troylynn Maupin (410) 328-3588 OPEN 940502.
MINNESOTA                 HIV Programs / Saint Paul Ramsey Medical
                          Center 640 Jackson St Paul, MN 55101 Contact:
                          Ray Nelson (612) 221-1280 OPEN 920729.
MISSOURI                  St Louis University / Div of Dermatology 1310
                          South Grand Boulevard St Louis, MO 63104
                          Contact: Corey Isenberg (314) 268-5215 OPEN
                          931110.
MISSOURI                  UM KC School of Medicine 2411 Holmes Kansas
                          City, MO 64108 Contact: Larry Simmons (816)
                          556-3554 CLOSED 940502.
MISSISSIPPI               Division of Infectious Diseases / UMC 2500
                          North State Street Jackson, MS 39216 Contact:
                          Harold Henderson (601) 984-5560 OPEN 920729.
NEW YORK                  Beth Israel Medical Center / Department of
                          Infect Diseases 1st Avenue at 16th Street New
                          York, NY 10003 Contact: Peter Berge (212)
                          420-4519 OPEN 931110.
NEW YORK                  Saint Vincents Hospital and Medical Center
                          412 Sixth Avenue / Fourth Flr New York, NY
                          10011 Contact: Noel George (212) 604-8319
                          OPEN 920729.
NEW YORK                  Mount Sinai Hospital / Clinical Trials Unit
                          One Gustave L Levy Place / Box 1042 New York,
                          NY 10029-6574 Contact: Dr Eileen Chusid (212)
                          241-8254 OPEN 931110.
NEW YORK                  University of Rochester Medical Center 601
                          Elmwood Avenue / Box 689 Rochester, NY 14642
                          Contact: Carol Greisberger (716) 275-0526
                          OPEN 920729.
OREGON                    Research and Education Group 2701 NW Vaughn
                          Street / Suite 770 Portland, OR 97210-5311
                          Contact: Norma Martinez (503) 229-8428
                          Contact: Robin Larson (503) 229-8428 OPEN
                          920729.
PENNSYLVANIA              University of Pittsburgh / IDM / Graduate Sch
                          of Public Hlth 130 DeSoto Street / Room A 454
                          / Crabtree Hall Pittsburgh, PA 15261 Contact:
                          Dr Deborah McMahon (412) 624-7883 CLOSED
                          940502.
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 931110.
RHODE ISLAND              Roger Williams Medical Center / Dept of Med /
                          Div of Derm 825 Chalkstone Avenue Providence,
                          RI 02908 Contact: Lisa Crandall (401)
                          456-6703 CLOSED 940502.
 
130
UNIQUE IDENTIFIER         FDA/00164
PROTOCOL ID NUMBERS       FDA 104A
PROTOCOL TITLE            A Study to Compare the Efficacy and Safety of
                          256U87 Versus Acyclovir in the Treatment of
                          Recurrent Anogenital Herpes Infections in HIV
                          Infected Patients.
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and efficacy
                          of oral 256U87 vs. acyclovir in the treatment
                          of recurrent anogenital herpes in
                          HIV-infected patients (CD4 = or > 100).
                          Methodology: Efficacy variables include the
                          length of the episode, the time to lesion
                          healing, the duration and severity of
                          pain/discomfort, the duration of viral
                          shedding, the proportion of patients with
                          aborted episodes, the proportion of patients
                          requiring extended therapy.
GENERAL DESCRIPTION       METHODOLOGY: Efficacy variables include the
                          length of the episode, the time to lesion
                          healing, the duration and severity of
                          pain/discomfort, the duration of viral
                          shedding, the proportion of patients with
                          aborted episodes, the proportion of patients
                          requiring extended therapy.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940502)
DISEASE STUDIED           Herpes simplex, anogenital.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: HIV-infected individual (CD4 = or
                          > 100) with a history of recurrent anogenital
                          herpes: 1. Having two or more recurrent
                          episodes within 6 months prior to beginning
                          the study OR 2. Patients previously on
                          chronic, suppressive acyclovir therapy during
                          the past year must experience at least one
                          recurrence after suppressive therapy is
                          discontinued. This recurrence must have
                          occurred within 3 months following the end of
                          suppressive therapy and within 3 months prior
                          to study enrollment. History of HSV
                          infections at genital, perirectal, or closely
                          associated sites (e.g., buttocks).
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    08
STUDY DESIGN              Drug Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 579 (940502).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 22 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have the following: HIV-infected individual
                          (CD4 = or > 100) with a history of recurrent
                          anogenital herpes. Signed the consent form or
                          present a signed parental consent form if
                          below 18 years. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CD4/CD8 RATION: >= 100.
PATIENT INCLUSION CRIT.   SGOT(AST): < 3 x ULN. ULN = upper limit of
                          normal.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 3 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study. Not breast-feeding. Not
                          pregnant.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following are excluded: Hepatic impairment as
                          evidenced by a three-fold increase from the
                          upper limit of normal in alanine or aspartate
                          transaminase. Impairment of renal function as
                          evidenced by any elevation above the upper
                          limit of normal for serum creatinine. History
                          of hypersensitivity to acyclovir.
                          Malabsorption or vomiting that would, in the
                          investigators opinion, potentially limit the
                          retention and absorption of oral therapy.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Breast-feeding.
                          Pregnant. No abstinence or no agreement to
                          use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Systemic
                          antiherpes or immunomodulatory therapy within
                          30 days prior to entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions or symptoms are excluded: Hepatic
                          impairments as evidenced by a three-fold
                          increase from the upper limit of normal in
                          alanine or aspartate transaminase. Impairment
                          of renal function as evidenced by any
                          elevation above the upper limit of normal for
                          serum creatinine. History of hypersensitivity
                          to acyclovir. Malabsorption or vomiting that
                          would, in the investigators opinion,
                          potentially limit the retention and absortion
                          of oral therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0119  Valaciclovir
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0008  Acyclovir
TRADE NAME OF SUBSTANCE   Drug 2 Zovirax
MANUFACTURERS             Drug 1: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
MANUFACTURERS             Drug 2: Burroughs Wellcome 3030 Cornwallis
                          Road Research Triangle, NC 27709 Contact:
                          Drug Information (800) 443-6763.
SUPPORTING AGENCY         Burroughs Wellcome.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Acyclovir/*THERAPEUTIC USE
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antiviral Agents/*THERAPEUTIC USE
MESH HEADING              Anus Diseases/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Herpes Genitalis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antiviral Agents)
CAS REGISTRY NUMBER       59277-89-3 (Acyclovir)
LAST REVISION DATE        940502
ENTRY MONTH               9108
ALABAMA                   Mobile, AL 36688 Contact: Dr Halim (205)
                          479-6933 CLOSED 940502.
CALIFORNIA                ViRx Incorporated 1375 Sutter Street / Suite
                          407 San Francisco, CA 94109 Contact: Joyce
                          Amann (415) 474-4440 Contact: Michael Baker
                          (415) 474-4440 OPEN 910807.
CALIFORNIA                San Francisco General Hospital 995 Portrero
                          Avenue Bldg 80 Ward 84 San Francisco, CA
                          94110 Contact: Patricia Duff (415) 431-0790
                          CLOSED 940502.
COLORADO                  Disease Control Services 605 Bannock Street
                          Denver, CO 80204 Contact: Joan Feil (303)
                          893-7123 CLOSED 940502.
CONNECTICUT               Veterans Administration Center / 111-1 950
                          Campbell Ave West Haven, CT 06516 Contact: Dr
                          Elizabeth Cooney (203) 932-5711 X 374CLOSED
                          940502.
FLORIDA                   University of South Florida 12901 North Bruce
                          Downs Boulevard Box 19 Tampa, FL 33612
                          Contact: Vicky Kenyon (813) 974-3163 CLOSED
                          940502.
GEORGIA                   Emory Medical School / Division of Infectious
                          Diseases 69 Butler Street Atlanta, GA 30303
                          Contact: Kara Barrett (404) 616-2440 OPEN
                          920301.
ILLINOIS                  Northwestern Memorial Hospital / Section of
                          Inf Dis 250 East Superior Street Chicago, IL
                          60611 Contact: Tamara Norman (312) 908-9636
                          OPEN 920301.
ILLINOIS                  Rush Presbyterian - St Lukes Medical Ctr /
                          Sec of Infect Dis 1725 West Harrison Ave
                          Suite 143 Academic Facility Chicago, IL 60612
                          Contact: Donna Samano (312) 942-5865 CLOSED
                          940502.
INDIANA                   Indiana University Medical School 545
                          Barnhill Drive EM 435 Division of Inf
                          Diseases Indianapolis, IN 46202 Contact: Beth
                          Zwickle (317) 274-8456 Contact: Heather Nixon
                          (317) 274-8456 CLOSED 940502.
LOUISIANA                 Louisianna State University Medical School /
                          Dept of Med 1542 Tulane Avenue HIV Program
                          New Orleans, LA 70112-2822 Contact: Marsha
                          Bennett (504) 568-5304 CLOSED 940502.
MISSISSIPPI               University of Mississippi Medical Center /
                          Div of Inf Dis 2500 North State Street
                          Jackson, MS 39216 Contact: Dr Harold
                          Henderson (601) 984-5560 CLOSED 940502.
NEW MEXICO                University of New Mexico / Sch of Medicine /
                          Dept of Med Division of Infectious Disease
                          HSSB 302 Box 608 Albuquerque, NM 87131
                          Contact: Marianne Butzinger (505) 277-5775
                          Contact: Marianne Butziner after 5 pm (505)
                          843-2111 CLOSED 940502.
NEW YORK                  St Vincents Hospital and Medical Center 412
                          Sixth Ave / 4th Floor New York, NY 10011
                          Contact: Noel George (212) 604-7625 CLOSED
                          940502.
OHIO                      University of Cincinnati / Medical Ctr / Div
                          of Infect Dis 231 Bethesda Ave Cincinnati, OH
                          45267-0560 Contact: Jarlath Black (513)
                          558-6977 Contact: (513) 558-2245 CLOSED
                          940502.
OREGON                    Research and Education Group 2701 North West
                          Vaughn Street / Suite 770 Portland, OR 97210
                          Contact: Norma Martinez (503) 229-8428 CLOSED
                          940502.
RHODE ISLAND              Roger Williams Medical Center / Dept of Med /
                          Div of Derm 825 Chalkstone Avenue Providence,
                          RI 02908 Contact: Lisa Crandall (401)
                          456-6703 CLOSED 940502.
 
131
UNIQUE IDENTIFIER         FDA/00655
PROTOCOL ID NUMBERS       FDA 088D
PROTOCOL TITLE            A Phase I Trial of Tecogalan sodium ( DS-4152
                          ) Administered as an Infusion Twice Weekly
                          for 21 Days.
VERSION NUMBER & DATE     (940804)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of different
                          doses and dosing regimens of tecogalan sodium
                          (DS-4152) and to establish the MTD at each of
                          the different dosing schedules. Methodology:
                          Patients receive intravenous DS-4152 by
                          infusion twice weekly for 21 days, followed
                          by 2 weeks of rest; courses may repeat.
                          Patients undergo weekly follow-up. A punch
                          biopsy will be obtained from patients with
                          Kaposi's sarcoma.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravenous
                          DS-4152 by infusion twice weekly for 21 days,
                          followed by 2 weeks of rest; courses may
                          repeat. Patients undergo weekly follow-up. A
                          punch biopsy will be obtained from patients
                          with Kaposi's sarcoma.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940801)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. EITHER histologically
                          confirmed Kaposi's sarcoma with a minimum of
                          four cutaneous lesions and no symptomatic
                          visceral involvement OR a metastatic solid
                          tumor that does not respond to therapy. 2.
                          HIV positive by ELISA and Western blot
                          (Kaposi's sarcoma patients ONLY). 3. NO
                          symptomatic AIDS-defining opportunistic
                          infection within the past 4 weeks.
ELIGIBILITY               AIDS. OTHER.
OTHER PROTOCOL NUMBERS    4152A-PRT005
STUDY DESIGN              Dose Comparison; Dose Escalating; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Maximum tolerated
                          dose (MTD), Drug dosing schedule.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Ongoing.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Kaposi's sarcoma plus HIV infection
                          OR metastatic solid tumor. 2. Life expectancy
                          of at least 12 weeks. 3. NO symptomatic
                          AIDS-defining opportunistic infection within
                          the past 4 weeks. 4. Recovered from toxicity
                          of any prior anticancer therapy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1200 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.25 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.25 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 2. (WHO scale).
PATIENT INCLUSION CRIT.   OTHER: WBC >= 2000 cells/mm3. PT and
                          activated PTT normal. Electrolytes, uric
                          acid, calcium, and phosphorus normal. Blood
                          glucose <= 280 mg/dl.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic gastrointestinal
                          bleeding or inflammatory bowel disease. 2.
                          History of myocardial infarction within past
                          6 months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Anticancer
                          therapy within the past 3 weeks (6 weeks for
                          nitrosourea or mitomycin C). 2.
                          Investigational agents within the past 4
                          weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          anticancer therapy. 2. Other investigational
                          agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Leukemia or lymphoma. 2. Current
                          gastrointestinal bleeding by stool guaiac. 3.
                          Extensive bone metastases or significant
                          radiographic osteoporosis in patients with
                          solid tumors. 4. Active heart disease such as
                          uncontrolled angina, uncompensated congestive
                          heart failure, or dysrhythmias requiring
                          antiarrhythmics. 5. Acute intercurrent
                          infection other than genital herpes. 6.
                          Symptomatic or known central nervous system
                          involvement (including brain metastases)
                          unless stable and off therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0217  Tecogalan sodium
TRADE NAME OF SUBSTANCE   Drug 1 DS-4152
MANUFACTURERS             Drug 1: Daiichi Pharmaceutical Corporation
                          400 Kelby Street / One Parker Plaza Fort Lee,
                          NJ 07024 Contact: Tom Boersig (201) 944-4333
                          X 212.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 infusion twice
                          weekly for 21 days
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Disease
                          progression. 2. Unacceptable toxicity.
SUPPORTING AGENCY         Daiichi Pharmaceutical Corporation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Neoplasms/*DRUG THERAPY
MESH HEADING              Polysaccharides, Bacterial/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antineoplastic Agents)
CAS REGISTRY NUMBER       134633-29-7 (DS 4152)
LAST REVISION DATE        940801
ENTRY MONTH               9409
CALIFORNIA                UCSS AIDS Program / San Francisco General
                          Hospital 995 Potereo Ave / Bldg 8 / Ward 84
                          San Francisco, CA 94110 Contact: Dr James
                          Kahn (415) 476-9296 OPEN 940801.
 
132
UNIQUE IDENTIFIER         FDA/00654
PROTOCOL ID NUMBERS       FDA 088C
PROTOCOL TITLE            A Phase I Trial of Tecogalan sodium ( DS-4152
                          ) Administered as an Infusion Twice Weekly
                          for 21 Days.
VERSION NUMBER & DATE     (940804)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of different
                          doses and dosing regimens of tecogalan sodium
                          (DS-4152) and to establish the MTD at each of
                          the different dosing schedules. Methodology:
                          Patients receive intravenous DS-4152 by
                          infusion twice weekly for 21 days, followed
                          by 2 weeks of rest; courses may repeat.
                          Patients undergo weekly follow-up. A punch
                          biopsy will be obtained from patients with
                          Kaposi's sarcoma.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravenous
                          DS-4152 by infusion twice weekly for 21 days,
                          followed by 2 weeks of rest; courses may
                          repeat. Patients undergo weekly follow-up. A
                          punch biopsy will be obtained from patients
                          with Kaposi's sarcoma.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930801)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. EITHER histologically
                          confirmed Kaposi's sarcoma with a minimum of
                          four cutaneous lesions and no symptomatic
                          visceral involvement OR a metastatic solid
                          tumor that does not respond to therapy. 2.
                          HIV positive by ELISA and Western blot
                          (Kaposi's sarcoma patients ONLY). 3. NO
                          symptomatic AIDS-defining opportunistic
                          infection within the past 4 weeks.
ELIGIBILITY               AIDS. OTHER.
OTHER PROTOCOL NUMBERS    4152A-PRT004
STUDY DESIGN              Dose Comparison; Dose Escalating; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Maximum tolerated
                          dose (MTD), Drug dosing schedule.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Ongoing.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Kaposi's sarcoma plus HIV infection
                          OR metastatic solid tumor. 2. Life expectancy
                          of at least 12 weeks. 3. NO symptomatic
                          AIDS-defining opportunistic infection within
                          the past 4 weeks. 4. Recovered from toxicity
                          of any prior anticancer therapy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1200 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.25 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.25 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 2. (WHO scale).
PATIENT INCLUSION CRIT.   OTHER: WBC >= 2000 cells/mm3. PT and
                          activated PTT normal. Electrolytes, uric
                          acid, calcium, and phosphorus normal. Blood
                          glucose <= 280 mg/dl.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic gastrointestinal
                          bleeding or inflammatory bowel disease. 2.
                          History of myocardial infarction within past
                          6 months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Anticancer
                          therapy within the past 3 weeks (6 weeks for
                          nitrosourea or mitomycin C). 2.
                          Investigational agents within the past 4
                          weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          anticancer therapy. 2. Other investigational
                          agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Leukemia or lymphoma. 2. Current
                          gastrointestinal bleeding by stool guaiac. 3.
                          Extensive bone metastases or significant
                          radiographic osteoporosis in patients with
                          solid tumors. 4. Active heart disease such as
                          uncontrolled angina, uncompensated congestive
                          heart failure, or dysrhythmias requiring
                          antiarrhythmics. 5. Acute intercurrent
                          infection other than genital herpes. 6.
                          Symptomatic or known central nervous system
                          involvement (including brain metastases)
                          unless stable and off therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0217  Tecogalan sodium
TRADE NAME OF SUBSTANCE   Drug 1 DS-4152
MANUFACTURERS             Drug 1: Daiichi Pharmaceutical Corporation
                          400 Kelby Street / One Parker Plaza Fort Lee,
                          NJ 07024 Contact: Tom Boersig (201) 944-4333
                          X 212.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 infusion twice
                          weekly for 21 days, followed by 2 weekof rest
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Disease
                          progression. 2. Unacceptable toxicity.
SUPPORTING AGENCY         Daiichi Pharmaceutical Corporation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Neoplasms/*DRUG THERAPY
MESH HEADING              Polysaccharides, Bacterial/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antineoplastic Agents)
CAS REGISTRY NUMBER       134633-29-7 (DS 4152)
LAST REVISION DATE        930801
ENTRY MONTH               9409
NEW YORK                  Memorial Sloan Kettering Cancer Center 1275
                          York Avenue / Room H-804 New York, NY 10021
                          Contact: Dr Susan Krown (212) 639-7426 OPEN
                          930801.
 
133
UNIQUE IDENTIFIER         FDA/00653
PROTOCOL ID NUMBERS       FDA 088B
PROTOCOL TITLE            A Phase I Trial of Tecogalan sodium ( DS-4152
                          ) Administered as an Infusion Weekly x 4.
VERSION NUMBER & DATE     (940804)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of different
                          doses and dosing regimens of tecogalan sodium
                          (DS-4152) and to establish the MTD at each of
                          the different dosing schedules. Methodology:
                          Patients receive intravenous DS-4152 by
                          infusion weekly for 4 weeks, followed by 2
                          weeks of rest; courses may repeat. Patients
                          undergo weekly follow-up. A punch biopsy will
                          be obtained from patients with Kaposi's
                          sarcoma.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravenous
                          DS-4152 by infusion weekly for 4 weeks,
                          followed by 2 weeks of rest; courses may
                          repeat. Patients undergo weekly follow-up. A
                          punch biopsy will be obtained from patients
                          with Kaposi's sarcoma.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930501)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. EITHER histologically
                          confirmed Kaposi's sarcoma with a minimum of
                          four cutaneous lesions and no symptomatic
                          visceral involvement OR a metastatic solid
                          tumor that does not respond to therapy. 2.
                          HIV positive by ELISA and Western blot
                          (Kaposi's sarcoma patients ONLY). 3. NO
                          symptomatic AIDS-defining opportunistic
                          infection within the past 4 weeks.
ELIGIBILITY               AIDS. OTHER.
OTHER PROTOCOL NUMBERS    4152A-PRT002
STUDY DESIGN              Dose Comparison; Dose Escalating; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Maximum tolerated
                          dose (MTD), Drug dosing schedule.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Ongoing.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Kaposi's sarcoma plus HIV infection
                          OR metastatic solid tumor. 2. Life expectancy
                          of at least 12 weeks. 3. NO symptomatic
                          AIDS-defining opportunistic infection within
                          the past 4 weeks. 4. Recovered from toxicity
                          of any prior anticancer therapy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1200 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <=1.25 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.25 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 2. (WHO scale).
PATIENT INCLUSION CRIT.   OTHER: WBC >= 2000 cells/mm3. PT and
                          activated PTT normal. Electrolytes, uric
                          acid, calcium, and phosphorus normal. Blood
                          glucose <= 280 mg/dl.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic gastrointestinal
                          bleeding or inflammatory bowel disease. 2.
                          History of myocardial infarction within past
                          6 months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Anticancer
                          therapy within the past 3 weeks (6 weeks for
                          nitrosourea or mitomycin C). 2.
                          Investigational agents within the past 4
                          weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          anticancer therapy. 2. Other investigational
                          agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Leukemia or lymphoma. 2. Current
                          gastrointestinal bleeding by stool guaiac. 3.
                          Extensive bone metastases or significant
                          radiographic osteoporosis in patients with
                          solid tumors. 4. Active heart disease such as
                          uncontrolled angina, uncompensated congestive
                          heart failure, or dysrhythmias requiring
                          antiarrhythmics. 5. Acute intercurrent
                          infection other than genital herpes. 6.
                          Symptomatic or known central nervous system
                          involvement (including brain metastases)
                          unless stable and off therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0217  Tecogalan sodium
TRADE NAME OF SUBSTANCE   Drug 1 DS-4152
MANUFACTURERS             Drug 1: Daiichi Pharmaceutical Corporation
                          400 Kelby Street / One Parker Plaza Fort Lee,
                          NJ 07024 Contact: Tom Boersig (201) 944-4333
                          X 212.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 infusion weekly
                          for 4 weeks, followed by 2 weeks of rest
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Disease
                          progression. 2. Unacceptable toxicity.
SUPPORTING AGENCY         Daiichi Pharmaceutical Corporation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Neoplasms/*DRUG THERAPY
MESH HEADING              Polysaccharides, Bacterial/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antineoplastic Agents)
CAS REGISTRY NUMBER       134633-29-7 (DS 4152)
LAST REVISION DATE        930501
ENTRY MONTH               9409
CALIFORNIA                Univ of Southern California / Kenneth Norris
                          Jr Cancer Ctr 1441 Eastlake Avenue / Room 162
                          Los Angeles, CA 90033 Contact: Dr Anil
                          Tulpule (213) 224-6668 OPEN 930501.
 
134
UNIQUE IDENTIFIER         FDA/00652
PROTOCOL ID NUMBERS       FDA 088A
PROTOCOL TITLE            A Phase I Trial of Tecogalan sodium ( DS-4152
                          ) Administered as an Infusion Every 21 Days.
VERSION NUMBER & DATE     (940804)
TRIAL CATEGORY            AIDS-Related Malignancies
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety of different
                          doses and dosing regimens of tecogalan sodium
                          (DS-4152) and to establish the MTD at each of
                          the different dosing schedules. Methodology:
                          Patients receive intravenous DS-4152 by
                          infusion once every 21 days; courses may
                          repeat. Patients undergo weekly follow-up. A
                          punch biopsy will be obtained from patients
                          with Kaposi's sarcoma.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravenous
                          DS-4152 by infusion once every 21 days;
                          courses may repeat. Patients undergo weekly
                          follow-up. A punch biopsy will be obtained
                          from patients with Kaposi's sarcoma.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930401)
DISEASE STUDIED           Kaposi's sarcoma.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. EITHER histologically
                          confirmed Kaposi's sarcoma with a minimum of
                          four cutaneous lesions and no symptomatic
                          visceral involvement OR a metastatic solid
                          tumor that does not respond to therapy. 2.
                          HIV positive by ELISA and Western blot
                          (Kaposi's sarcoma patients ONLY). 3. NO
                          symptomatic AIDS-defining opportunistic
                          infection within the past 4 weeks.
ELIGIBILITY               AIDS. OTHER.
OTHER PROTOCOL NUMBERS    4152A-PRT001
STUDY DESIGN              Dose Comparison; Dose Escalating; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Maximum tolerated
                          dose (MTD), Drug dosing schedule.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Ongoing.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Kaposi's sarcoma plus HIV infection
                          OR metastatic solid tumor. 2. Life expectancy
                          of at least 12 weeks. 3. NO symptomatic
                          AIDS-defining opportunistic infection within
                          the past 4 weeks. 4. Recovered from toxicity
                          of any prior anticancer therapy. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1200 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 100000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 1.25 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 2.0 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.25 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 60 ml/min. (if
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 2. (WHO scale).
PATIENT INCLUSION CRIT.   OTHER: WBC >= 2000 cells/mm3. PT and
                          activated PTT normal. Electrolytes, uric
                          acid, calcium, and phosphorus normal. Blood
                          glucose <= 280 mg/dl.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of acute or chronic gastrointestinal
                          bleeding or inflammatory bowel disease. 2.
                          History of myocardial infarction within past
                          6 months. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Anticancer
                          therapy within the past 3 weeks (6 weeks for
                          nitrosourea or mitomycin C). 2.
                          Investigational agents within the past 4
                          weeks.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          anticancer therapy. 2. Other investigational
                          agents.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Leukemia or lymphoma. 2. Current
                          gastrointestinal bleeding by stool guaiac. 3.
                          Extensive bone metastases or significant
                          radiographic osteoporosis in patients with
                          solid tumors. 4. Active heart disease such as
                          uncontrolled angina, uncompensated congestive
                          heart failure, or dysrhythmias requiring
                          antiarrhythmics. 5. Acute intercurrent
                          infection other than genital herpes. 6.
                          Symptomatic or known central nervous system
                          involvement (including brain metastases)
                          unless stable and off therapy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0217  Tecogalan sodium
TRADE NAME OF SUBSTANCE   Drug 1 DS-4152
MANUFACTURERS             Drug 1: Daiichi Pharmaceutical Corporation
                          400 Kelby Street / One Parker Plaza Fort Lee,
                          NJ 07024 Contact: Tom Boersig (201) 944-4333
                          X 212.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 1 infusion q 21 days
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Disease
                          progression. 2. Unacceptable toxicity.
SUPPORTING AGENCY         Daiichi Pharmaceutical Corporation.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antineoplastic Agents/ADMINISTRATION & DOSAGE/
                          *ADVERSE EFFECTS
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Neoplasms/*DRUG THERAPY
MESH HEADING              Polysaccharides, Bacterial/ADMINISTRATION &
                          DOSAGE/*ADVERSE EFFECTS
MESH HEADING              Sarcoma, Kaposi's/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Antineoplastic Agents)
CAS REGISTRY NUMBER       134633-29-7 (DS 4152)
LAST REVISION DATE        930401
ENTRY MONTH               9409
 
135
UNIQUE IDENTIFIER         FDA/00620
PROTOCOL ID NUMBERS       FDA 087A
PROTOCOL TITLE            A Randomized, Controlled, Multicenter Trial
                          of Filgrastim (Recombinant-methionyl Human
                          Granulocyte Colony Stimulating Factor; G-CSF)
                          for the Prevention of Grade 4 Neutropenia in
                          Patients With HIV Infection.
VERSION NUMBER & DATE     (940112)
TRIAL CATEGORY            HIV Infection
GENERAL DESCRIPTION       PURPOSE: To determine, in HIV-infected
                          patients, the efficacy of filgrastim
                          (recombinant-methionyl human
                          granulocyte-colony stimulating factor; G-CSF)
                          in preventing grade 4 neutropenia, i.e.,
                          absolute neutrophil count (ANC) < 500
                          cells/mm3. Methodology: Patients are
                          randomized to receive subcutaneous G-CSF at
                          one of two different doses or no G-CSF
                          (observation) for 24 weeks. Patients who
                          experience ANC < 500 cells/mm3 on two
                          consecutive occasions at least 24 hours apart
                          prior to completing the 24-week study period
                          will be considered to have reached the
                          primary study endpoint; those in the
                          observation group who reach the primary
                          endpoint prior to week 24 may begin receiving
                          G-CSF for the remainder of the study period.
                          After 24 weeks, patients may continue G-CSF
                          on a compassionate basis at the
                          investigator's discretion.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive subcutaneous G-CSF at one of two
                          different doses or no G-CSF (observation) for
                          24 weeks. Patients who experience ANC < 500
                          cells/mm3 on two consecutive occasions at
                          least 24 hours apart prior to completing the
                          24-week study period will be considered to
                          have reached the primary study endpoint;
                          those in the observation group who reach the
                          primary endpoint prior to week 24 may begin
                          receiving G-CSF for the remainder of the
                          study period. After 24 weeks, patients may
                          continue G-CSF on a compassionate basis at
                          the investigator's discretion.
PROTOCOL PHASE            Phase II / Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940112)
DISEASE STUDIED           Neutropenia.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive by ELISA
                          confirmed by Western blot OR documented
                          history of AIDS by CDC definition. 2. CD4
                          count < 200 cells/mm3. 3. ANC (segmental
                          neutrophils plus bands) >= 750 and < 1000
                          cells/mm3 on one occasion within 7 days prior
                          to study entry. NOTE: Stable Kaposi's sarcoma
                          is permitted provided patient does not
                          require myelosuppressive therapy (other than
                          interferon) within 4 weeks prior to study
                          entry.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GCSF-930101
STUDY DESIGN              Randomized; Controlled; Open Label;
                          Multicenter; Dose Comparison
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug
                          prophylaxis.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 250 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 24
                          weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 22 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection OR history
                          of AIDS. 2. CD4 count < 200 cells/mm3. 3. ANC
                          (segmental neutrophils plus bands) >= 750 and
                          < 1000 cells/mm3 within 7 days prior to study
                          entry. 4. Life expectancy of at least 6
                          months. NOTE: Stable Kaposi's sarcoma is
                          permitted provided patient does not require
                          myelosuppressive therapy (other than
                          interferon) within 4 weeks prior to study
                          entry. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 200 cells/mm3. ( 0 -
                          100 ).
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50.
PATIENT INCLUSION CRIT.   OTHER: ANC >= 750 and < 1000 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Prior
                          antiretroviral agents (e.g., AZT,
                          ganciclovir, ddI, ddC),
                          trimethoprim-sulfamethoxazole (Bactrim),
                          interferon, and amphotericin B.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed:
                          Antiretroviral agents (e.g., AZT,
                          ganciclovir, ddI, ddC),
                          trimethoprim-sulfamethoxazole (Bactrim),
                          interferon, and amphotericin B ONLY IF
                          patient is on the same dose for at least 14
                          days prior to study entry (patients may not
                          start or stop these agents within 14 days
                          prior to study entry).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Substance abuse the would
                          compromise compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: G-CSF, other
                          hematopoietic growth factors (except for
                          erythropoietin), or investigational agents
                          within 14 days prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Malignancy other than Kaposi's sarcoma and
                          localized basal or squamous cell carcinoma.
                          2. Psychiatric, addictive, or other disorder
                          that compromises ability to give informed
                          consent. 3. Known hypersensitivity to E.
                          coli-derived products.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0086  Granulocyte
                          colony-stimulating factor
TRADE NAME OF SUBSTANCE   Drug 1 Neupogen
MANUFACTURERS             Drug 1: Amgen Inc Amgen Center Thousand Oaks,
                          CA 91320-1789 Contact: David Kaye (805)
                          447-6692.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Injected at one of
                          two doses for at least 24 weeks
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 24 weeks.
OTHER TREATMENT INFO.     END POINT: Development of neutropenia.
SUPPORTING AGENCY         Amgen Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Granulocyte Colony-Stimulating Factor/
                          *ADMINISTRATION & DOSAGE/THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Neutropenia/COMPLICATIONS/*PREVENTION &
                          CONTROL
CAS REGISTRY NUMBER       62683-29-8 (Granulocyte Colony-Stimulating
                          Factor)
LAST REVISION DATE        940112
ENTRY MONTH               9404
ALABAMA                   University of Alabama / AIDS Outpatient
                          Clinic 908 South 20th Street Birmingham, AL
                          35294 Contact: Jill Weingarten (205) 934-3690
                          Contact: Dr Jill Weingarten (205) 934-1714
                          OPEN 940112.
ARIZONA                   Maricopa County Medical Center 2601 East
                          Roosevelt Phoenix, AZ 85008 Contact: Emily
                          Cardoza (602) 681-1100 OPEN 940112.
CALIFORNIA                UCLA / CARE Center 10833 Le Conte Ave Los
                          Angeles, CA 90024 Contact: Susie McCarthy
                          (310) 206-6414 OPEN 940112.
CALIFORNIA                San Francisco General Hospital 1001 Potrero
                          Avenue Building 80 Ward 84 San Francisco, CA
                          94110 Contact: Mary Payne (415) 476-4082 X
                          846OPEN 940112.
CALIFORNIA                Sunnybrook Health Science Center 2075 Bayview
                          Avenue Toronto, CA M4N 3M5 Contact: Miriam
                          Bast (416)480-4689 OPEN 940112.
CALIFORNIA                The Toronto Hospital 200 Elizabeth Street /
                          CW Ground 325 Toronto, CA M5G 2C9 Contact:
                          Susan Klys (416)340-4239 OPEN 940112.
CALIFORNIA                St Michael Hospital 30 Bond Street Toronto,
                          CA M5B 1W8 Contact: Manual Laurel
                          (416)864-5746 OPEN 940112.
CALIFORNIA                Hotel - Dieu de Montreal 3981 St. Laurent
                          Blvd / Mezz 1 Montreal, CA H2W 1Y5 Contact:
                          Catherine L'Homme 5148432712 OPEN 940112.
CALIFORNIA                The Wellesley Hospital Toronto, CA M5B 1WB
                          Contact: Barry Milton (416)926-7728 OPEN
                          940112.
COLORADO                  University Hospital / Univ of Colorado Health
                          Sci Ctr Box B-163 / 4200 East Ninth Avenue
                          Denver, CO 80262 Contact: Graham Ray (303)
                          270-8551 OPEN 940112 ACTU: 0105.
DISTRICT OF COLUMBIA      George Washington University / Medical Center
                          / Div Inf Dise 2150 Pennsylvania Ave NW
                          Washington, DC 20037 Contact: Susan
                          LeLacheruri (202) 994-2417 OPEN 940112.
FLORIDA                   Therafirst Medical Center 4011 N Federal
                          Highway Ft Lauderdale, FL 33308 Contact:
                          Denise LaMarca (305) 564-4222 OPEN 940112.
ILLINOIS                  Rush Presbyterian - St Lukes / Northwestern
                          University 303 East Superior Street Rm 823
                          Chicago, IL 60611 Contact: Baiba L Berzins
                          (312) 908-9636 OPEN 940112 ACTU: 2702.
KANSAS                    University of Kansas / School of Medicine
                          1010 N Kansas Wichita, KS 67214 Contact:
                          Katherine Thiessen (316) 261-2655 OPEN
                          940112.
LOUISIANA                 Tulane University Medical School / AIDS
                          Clinical Trials Unit 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Russell
                          Strada (504) 584-3605 OPEN 940112.
MASSACHUSETTS             New England Deaconess Hospital 110 Francis
                          Street Boston, MA 02215 Contact: Judy
                          Tessitore (617) 632-8514 Contact: Dr David
                          Scadden (617) 632-8540 OPEN 940112.
NORTH CAROLINA            Nalle Clinic 1350 South Kings Drive
                          Charlotte, NC 28287 Contact: Jan Caldwell
                          (704) 342-8100 Contact: Dr Joseph Jemsek
                          (704) 342-8318 OPEN 940112.
NEW YORK                  SUNY at Stony Brook HSC T15 080 Stony Brook,
                          NY 11794 Contact: Christine Wallace (516)
                          444-3904 OPEN 940112.
OHIO                      University Hospitals of Cleveland/Case
                          Western Reserve Univ 206 Cornell Road
                          Cleveland, OH 44106 Contact: Michael Chance
                          (216) 844-8175 OPEN 940112.
OREGON                    Northwest Kaiser Permanente Med Ctr / Dept of
                          Hemat/Oncol 3414 N Kaiser Center Drive
                          Portland, OR 97227 Contact: Michael Allison
                          (503) 249-3313 Contact: Dr Mark Rarick (503)
                          249-3430 OPEN 940112.
OTHER                     St Paul Hospital 1061 Burrard Street
                          Vancouver, BC V6Z 1Y6 Contact: Dr Kathy
                          Mandigo 6046822344 x3176 OPEN 940112.
 
136
UNIQUE IDENTIFIER         FDA/00563
PROTOCOL ID NUMBERS       FDA 085A
PROTOCOL TITLE            A Phase I Study of Subcutaneously
                          Administered Recombinant Interleukin-2
                          (Aldesleukin; Proleukin) in HIV-Infected
                          Patients.
VERSION NUMBER & DATE     (930811)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To determine the MTD and
                          dose-limiting toxicities of recombinant
                          interleukin-2 (aldesleukin; Proleukin)
                          administered subcutaneously in
                          HIV-seropositive patients. To identify a
                          tolerable subcutaneous regimen that will
                          replicate the immunologic improvement
                          demonstrated in the outpatient polyethylene
                          glycolated IL-2 and high-dose continuous
                          infusion IL-2 studies. To evaluate the
                          incidence and level of anti-IL-2 antibody
                          formation to subcutaneously administered
                          Proleukin in this patient population.
                          Methodology: Patients will receive
                          subcutaneous Proleukin, and the MTD will be
                          determined.
GENERAL DESCRIPTION       METHODOLOGY: Patients will receive
                          subcutaneous Proleukin, and the MTD will be
                          determined.
PROTOCOL PHASE            Phase I
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941018)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection by
                          ELISA and Western blot. 2. CD4 count > 200
                          cells/mm3.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    CS-L293-09. BB-IND 5223
STUDY DESIGN              Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Maximum tolerated dose (MTD),
                          Drug safety, Drug tolerance, Immunotherapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection by ELISA
                          and Western blot. 2. CD4 count > 200
                          cells/mm3. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 9 g/dl.
PATIENT INCLUSION CRIT.   GRANULOCYTES: >= 1000 cells/mm3.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: > 200 cells/mm3. ( 200 -
                          300 - 400 - 500 - 600 - 700 - 800 - plus ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 70.
PATIENT INCLUSION CRIT.   OTHER: Proteinuria <= 1+.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: FDA-approved
                          antiretroviral therapy for at least 2 months
                          prior to study entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0021  Interleukin-2
TRADE NAME OF SUBSTANCE   Drug 1 Proleukin
MANUFACTURERS             Drug 1: Cetus Corporation 1400 Fifty-Third
                          Street Emeryville, CA 94608 Contact:
                          Professional Services (800) 238-8779.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous (SC)
SUPPORTING AGENCY         Cetus Corporation.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Interleukin-2/*ADVERSE EFFECTS
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Interleukin-2)
LAST REVISION DATE        941018
ENTRY MONTH               9310
CALIFORNIA                Davies Medical Center / Institute - HIV
                          Research & Treatment Castro and Duboce
                          Streets San Francisco, CA 94114 Contact: Dr
                          Stephen Follansbee (415) 565-6153 Contact:
                          (415) 565-6524 OPEN 930811.
 
137
UNIQUE IDENTIFIER         FDA/00464
PROTOCOL ID NUMBERS       FDA 083A
PROTOCOL TITLE            Treatment of Patients With Human
                          Immunodeficiency Virus (HIV)-Related Chronic
                          Diarrhea With Saccharomyces boulardii or
                          Placebo: A Double Blind Trial.
VERSION NUMBER & DATE     (940304)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Surawicz CM
GENERAL DESCRIPTION       PURPOSE: To assess the efficacy of
                          Saccharomyces boulardii (a nonpathogenic
                          yeast) in producing a significant reduction
                          in diarrheal symptoms in HIV-infected
                          patients with chronic diarrhea
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940304)
DISEASE STUDIED           Diarrhea.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection. 2.
                          Chronic diarrhea (for at least 1 month) that
                          is either a manifestation or complication of
                          documented HIV infection. 3. Has had a stool
                          culture (Salmonella, Shigella, Campylobacter,
                          and Clostridium difficile) and stool analysis
                          for ova and parasite (O/P X 3) within the
                          past 2 months. 4. Has completed a specific
                          course of antimicrobial treatment for
                          diarrhea, if indicated, but was unresponsive
                          (diarrhea still present), OR no
                          antimicrobials for stool pathogens were
                          administered because stool cultures were
                          negative. Patients who are on antiviral
                          medications for HIV infection must have
                          received such medication for at least 2 weeks
                          and must remain on stable dose for weeks 1
                          and 2 of study.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    BB-IND 2065
STUDY DESIGN              Double-Blind; Placebo-Controlled; Randomized
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 100 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 3 months (2
                          months on drug and 1 month follow-up).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. Chronic
                          diarrhea (for at least 1 month) that is
                          either a manifestation or complication of
                          documented HIV infection. 3. Had a stool
                          culture (Salmonella, Shigella, Campylobacter,
                          and Clostridium difficile) and stool analysis
                          for ova and parasite (O/P X 3) within the
                          past 2 months. 4. Failed antimicrobial
                          treatment for diarrhea OR received no prior
                          antimicrobials for stool pathogens because
                          stool cultures were negative. Patients who
                          are on antiviral medications for HIV
                          infection must have received such medication
                          for at least 2 weeks and must remain on
                          stable dose for weeks 1 and 2 of study.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: 1. Prior antiviral
                          medication for HIV infection (if on such
                          medication, must have received it for at
                          least 2 weeks). 2. Standard antimicrobial
                          therapy for a documented positive
                          gastrointestinal pathogen.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Antiviral
                          medication for HIV infection.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Gastrointestinal medications that cause
                          diarrhea (e.g., magnesium-containing
                          antacids, lactulose). 2. Maintenance
                          antifungal medication for life-threatening
                          fungal infections (other than fluconazole <=
                          100 mg/day).
PATIENT EXCLUSION CRIT.   AVAILABILITY: Patients with no telephone in
                          residence are not eligible.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0149  Saccharomyces boulardii
MANUFACTURERS             Drug 1: Biocodex Inc 1910 Fairview Avenue E /
                          Suite 208 Seattle, WA 98102-3699 Contact:
                          Kris Moyer (206) 322-5602.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, capsules
SUPPORTING AGENCY         Biocodex Inc.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Diarrhea/COMPLICATIONS/*THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Saccharomyces/*PHYSIOLOGY
LAST REVISION DATE        940304
ENTRY MONTH               9210
 
138
UNIQUE IDENTIFIER         FDA/00607
PROTOCOL ID NUMBERS       FDA 059F
PROTOCOL TITLE            A Randomized Study Comparing the Safety and
                          Efficacy of Three Doses of Oral Ganciclovir
                          to Intravenous Ganciclovir for the
                          Maintenance Treatment of Cytomegalovirus
                          Retinitis in People With AIDS.
VERSION NUMBER & DATE     (940316)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To compare the time to progression
                          of Cytomegalovirus (CMV) retinitis among each
                          of three doses of oral ganciclovir (3000,
                          4500, and 6000 mg daily), as well as to
                          intravenous therapy (5 mg/kg daily), when
                          given as maintenance for 26 weeks. To compare
                          the safety and tolerance among oral doses of
                          ganciclovir at the study doses, as well as to
                          intravenous therapy, when administered as
                          maintenance for 26 weeks. Methodology:
                          Patients who have received anti-CMV therapy
                          with intravenous ganciclovir for at least 4
                          weeks that resulted in stable retinitis are
                          randomized to receive one of three doses of
                          oral ganciclovir or intravenous ganciclovir
                          for 26 weeks of maintenance.
GENERAL DESCRIPTION       METHODOLOGY: Patients who have received
                          anti-CMV therapy with intravenous ganciclovir
                          for at least 4 weeks that resulted in stable
                          retinitis are randomized to receive one of
                          three doses of oral ganciclovir or
                          intravenous ganciclovir for 26 weeks of
                          maintenance.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940613)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV positive by antibody test,
                          p24 antigen assay, or HIV culture, or
                          diagnosis of AIDS by CDC criteria. 2. No more
                          than two episodes of CMV retinitis
                          progression (relapse resulting in reinduction
                          with intravenous anti-CMV therapy) since the
                          original retinitis diagnosis. 3. Currently
                          stable retinitis, defined as inactive CMV
                          retinal lesions or as progression that has
                          halted following at least 4 weeks of
                          intravenous ganciclovir therapy immediately
                          prior to study entry. (If retinal lesions are
                          not inactive, stability of the retinitis must
                          have been confirmed based on the last two
                          ophthalmologic exams.)
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GANs2226
STUDY DESIGN              Randomized; Dose Comparison; Comparative
                          administration route; Drug Tolerance;
                          Parallel-Group; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Administration route comparison.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 280 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 26 weeks.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 8/280 (940218).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 36 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV positive. 2. No more than two
                          episodes of CMV retinitis progression
                          (relapse resulting in reinduction with
                          intravenous anti-CMV therapy) since the
                          original retinitis diagnosis. 3. Currently
                          stable retinitis. [Refer to Laboratory values
                          for additional requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 25000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Foscarnet prior to
                          the 4 weeks of intravenous induction therapy.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Topical and
                          ophthalmic nucleoside analogs.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of hypersensitivity to acyclovir or
                          ganciclovir. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. More than
                          three induction regimens with intravenous
                          anti-CMV therapy. 2. Any prior oral
                          ganciclovir.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Acyclovir
                          sodium (Zovirax) by any route other than
                          topical. 2. Valaciclovir. 3. Brovavir. 4.
                          Vidarabine. 5. Amantadine hydrochloride. 6.
                          Cytarabine. 7. Idoxuridine. 8. Ribavirin. 9.
                          Interferon. 10. Foscarnet (non-nucleoside
                          pyrophosphate analog). 11. CMV hyperimmune
                          globulin. 12. Soluble CD4. 13. Trichosanthin
                          (Compound Q). 14. Imipenem-cilastatin. 15.
                          Isoprinosine. 16. Levamisole. 17. Other
                          investigational drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Persistent or clinically significant
                          diarrhea, nausea, or abdominal pain. 2.
                          Severe odynophagia. 3. Other gastrointestinal
                          (GI) symptoms or uncontrolled GI disease. 4.
                          Active CMV disease of the GI tract (e.g., CMV
                          colitis, CMV esophagitis). 5. Ocular media
                          opacities (corneal, lenticular, or vitreal)
                          that prevent ophthalmologic retinal
                          assessments. 6. Dementia, decreased
                          mentation, or other encephalopathic signs and
                          symptoms that would preclude informed consent
                          or study compliance.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0018  Ganciclovir
TRADE NAME OF SUBSTANCE   Drug 1 Cytovene
MANUFACTURERS             Drug 1: Syntex Research 3401 Hillview Avenue
                          / PO Box 10850 / Mail Stop A4-HPRA Palo Alto,
                          CA 94303 Contact: Bonnie Charpentier (415)
                          354-2344.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Oral dose: 1000,
                          1500, or 2000 mg TID for 26 weeks.
                          Intravenous dose: 5 mg/kg daily for 26 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Oral: 3000, 4500, or
                          6000 mg. Intravenous: 5 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral or intravenous
                          (IV)
OTHER TREATMENT INFO.     TREATMENT DURATION: 26 weeks.
SUPPORTING AGENCY         Syntex Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Ganciclovir/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       82410-32-0 (Ganciclovir)
LAST REVISION DATE        940613
ENTRY MONTH               9403
ALABAMA                   University of Alabama / AIDS Outpatient
                          Clinic 908 South 20th Street Birmingham, AL
                          35294 Contact: Jill Weingarten (205) 934-3690
                          Contact: Dr Jill Weingarten (205) 934-1714
                          OPEN 940218.
ARIZONA                   McDowell Clinic 1314 East McDowell Phoenix,
                          AZ 85006 Contact: Mary Mulrow (602) 267-5011
                          OPEN 940218.
ARIZONA                   Dr Ken Fisher 1444 West Betharmy Home Road
                          Phoenix, AZ 85013 Contact: Ken Reed (602)
                          433-7712 OPEN 940218.
ARIZONA                   University of Arizona / Section of Infectious
                          Diseases 1501 North Campbell Avenue Tucson,
                          AZ 85724 Contact: Joel Gray (602) 626-2533
                          OPEN 940218.
CALIFORNIA                UCLA AIDS Clinical Research Center / BH-412
                          CHS 10833 Le Conte Avenue / BH - 412 / CHS
                          Los Angeles, CA 90024-1793 Contact: Suzette
                          Chafey (310) 206-6414 Contact: Dr David Hardy
                          (310) 206-3474 OPEN 940218.
CALIFORNIA                University of California San Diego Medical
                          Center / Dept Ped H - 814 - H / 225 Dickenson
                          San Diego, CA 92103 Contact: Linda Meixner
                          (619) 534-7170 OPEN 940218.
CALIFORNIA                Davies Medical Center / Institute for HIV
                          Treatment and Rsch Castro and Duboce Streets
                          San Francisco, CA 94114 Contact: Sue Kelly
                          (415) 565-6153 OPEN 940218.
CALIFORNIA                Mt Zion Hospital and Medical Center / Dep of
                          Clinical Micro 1600 Divisadero / Second Floor
                          San Francisco, CA 94115 Contact: Craig James
                          (415) 476-6356 OPEN 940218.
CALIFORNIA                San Francisco Veterans' Administration
                          Medical Center 4150 Clement Street #111W San
                          Francisco, CA 94121 Contact: Manon Marovich
                          (415) 221-4810 X 394Contact: Sandra Charles
                          (415) 221-4810 X 394OPEN 940218 ACTU: 0807.
CALIFORNIA                East Bay AIDS Clinic 3031 Telegraph Avenue
                          Berkeley, CA 94705 Contact: Nancy Orcutt
                          (510) 204-1870 OPEN 940218.
DISTRICT OF COLUMBIA      George Washington Medical Center / Division
                          Infectious Disea Room 5-408 / 2150
                          Pennsylvania Avenue Washington, DC 20037
                          Contact: Dr David Parenti (202) 994-3949 OPEN
                          940218.
FLORIDA                   Community Research Initiative 1506 San
                          Ignacio Avenue / Suite 200 Coral Gables, FL
                          33146 Contact: Lexi East (305) 667-9296 OPEN
                          940218.
GEORGIA                   AIDS Research Consortium of Atlanta 131 Ponce
                          de Leon / Suite 130 Atlanta, GA 30308
                          Contact: Lisa Ferrigno (404) 876-2317 OPEN
                          940218.
HAWAII                    Margo Heath-Chiozzi 3675 Kilauea Avenue /
                          Young Bldg / Room 16E Honolulu, HI 96816
                          Contact: Sue Congdon (808) 737-0036 OPEN
                          940218.
MARYLAND                  University of Maryland School of Medicine /
                          Research Service 10 North Green Street
                          Baltimore, MD 21201 Contact: Dr Susan Keay
                          (410) 605-7000 X 645OPEN 940218.
MISSOURI                  AIDS Clinical Trials Unit 4511 Forest Park /
                          Suite 304 St Louis, MO 63108 Contact: Janet
                          Voorhese (314) 454-0058 OPEN 940218.
NORTH CAROLINA            University of North Carolina at Chapel Hill /
                          UNC CTU 516 Burnett Womack / CB# 7215 Chapel
                          Hill, NC 27599-7215 Contact: Barbara Longmire
                          (919) 966-7883 OPEN 940218.
NORTH CAROLINA            Nalle Clinic 1350 South Kings Drive
                          Charlotte, NC 28207-2198 Contact: Angela
                          Chouffani (704) 344-2280 OPEN 940218.
NEW MEXICO                University of New Mexico / Department of
                          Medicine HSSB - 302 Albuquerque, NM 87131
                          Contact: Maria Fernando-Fletcher (505)
                          277-8207 OPEN 940218.
NEW MEXICO                AIDS Wellness Clinic 811 St Michaels Drive /
                          Suite P Sante Fe, NM 87501 Contact: Patty
                          Dally (505) 983-1822 OPEN 940218.
NEVADA                    AIDS Outpatient Services / University Medical
                          Center 1800 West Charleston Blvd Las Vegas,
                          NV 89102 Contact: Ann Occhl (702) 383-7075
                          OPEN 940218.
NEW YORK                  Dr Dorothy Friedberg 310 Lexington Avenue New
                          York, NY 10016 Contact: Kathleen Farrell
                          (212) 263-6485 Contact: Dr Dorothy Friedberg
                          (212) 263-8473 OPEN 940218.
NEW YORK                  St Lukes - Roosevelt Hospital / AIDS Clinical
                          Trials Program 432 West 58th Street New York,
                          NY 10019 Contact: Brenda Kolatch (212)
                          523-6743 OPEN 940218.
NEW YORK                  The New York Hospital / Cornell Medical
                          Center 525 East 68th Street / Baker 24 New
                          York, NY 10021 Contact: Sandi Slertz (212)
                          748-4177 OPEN 940218.
OHIO                      Ohio State University School of Medicine 456
                          West Tenth Avenue / Room 4725 Columbus, OH
                          43210-1228 Contact: Judith Neidig (614)
                          293-8112 Contact: (614) 293-5282 OPEN 940218.
OHIO                      Case Western Reserve University / ACTG 2061
                          Cornell Road Room 120 Cleveland, OH
                          44106-4984 Contact: Michael Chance (216)
                          844-8051 OPEN 940218 ACTU: 2501.
OKLAHOMA                  Associates in Medical and Mental Health 1560
                          East 21st Street / Suite 210 Tulsa, OK
                          74114-1325 Contact: Virginia Butler (918)
                          743-1000 OPEN 940218.
OREGON                    Veterans Administration Portland Medical
                          Center Dept of Research & Education / 2701 NW
                          Vaughn / Suite 770 Portland, OR 97210
                          Contact: Dr James H Sampson (503) 229-8428
                          OPEN 940218.
OTHER                     St Paul's Hospital Room C - 371 / 1061
                          Burrard Street Vancouver, BC V6Z 1Y6 Contact:
                          Ginna Bell 8046822344 OPEN 940218.
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 940218.
 
139
UNIQUE IDENTIFIER         FDA/00486
PROTOCOL ID NUMBERS       FDA 058J
PROTOCOL TITLE            Oral/Intravenous Azithromycin in the
                          Treatment of Cryptosporidiosis in Patients
                          Whose Disease Has Not Been Controlled by
                          Conventional Therapy.
VERSION NUMBER & DATE     (940311)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
GENERAL DESCRIPTION       PURPOSE: To provide azithromycin for the
                          treatment of individual patients with proven
                          cryptosporidiosis whose disease has persisted
                          or progressed despite prior therapies.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940505)
DISEASE STUDIED           Cryptosporidiosis / diarrhea.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Cryptosporidiosis infection
                          proven by stool examination on at least two
                          occasions, one within 4 weeks prior to study
                          entry, or verified by endoscopic biopsy.
                          Other treatable causes of diarrhea must have
                          been excluded. 2. Must have failed or been
                          intolerant to prior therapy with standard
                          antidiarrheal or antibiotic or other
                          therapies for cryptosporidiosis. Patients
                          with documented favorable response to
                          azithromycin under Pfizer protocol 066-143
                          may receive maintenance therapy under this
                          protocol.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-167S
PROTOCOL DETAILS          STUDY INTENT: Drug therapy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 49 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Cryptosporidiosis infection. 2. Life
                          expectancy of at least 1 week. 3. Must have
                          failed or been intolerant to prior therapy
                          with standard antidiarrheal or antibiotic or
                          other therapies for cryptosporidiosis. 4.
                          Consent of parent or guardian for patients
                          under the legal age of consent. Patients with
                          documented favorable response to azithromycin
                          under Pfizer protocol 066-143 may receive
                          maintenance therapy under this protocol.
                          Patients with persistent diarrhea requiring
                          intravenous (IV) fluid therapy to maintain
                          hydration may receive IV azithromycin after
                          approval by the clinical monitor. Patients
                          whose disease worsens despite a minimum of 2
                          weeks of oral therapy or patients whose
                          disease shows no improvement after 4 weeks of
                          oral therapy will also be considered for a
                          trial period of intravenous azithromycin.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 01 Days - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Must have failed
                          or been intolerant to prior therapy with
                          standard antidiarrheal or antibiotic
                          therapies for cryptosporidiosis.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: No abstinence or no
                          agreement to use effective method of birth
                          control / contraception during the study.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          hypersensitivity or significant intolerance
                          to macrolide antibiotics. 2. Eligibility and
                          current treatment at a medical center
                          performing study 066-143, another study of
                          azithromycin for treatment of
                          cryptosporidiosis in AIDS patients.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
TRADE NAME OF SUBSTANCE   Drug 1 CP-62,933
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, intravenous
SUPPORTING AGENCY         Pfizer Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Antidiarrheals/THERAPEUTIC USE
MESH HEADING              Azithromycin/*THERAPEUTIC USE
MESH HEADING              Child
MESH HEADING              Cryptosporidiosis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Diarrhea/COMPLICATIONS/DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       0 (Antidiarrheals)
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        940505
ENTRY MONTH               9301
ALASKA                    Dr Frank Domurat 1200 Airport Heights Drive
                          Suite 300 Anchorage, AK 99508 Contact: Dr
                          Frank Domurat (907) 278-3155 OPEN 940627.
ARIZONA                   Cigna 755 East McDowell Road Phoenix, AZ
                          85006 Contact: Dr Dean Martin (602) 271-3762
                          OPEN 930111.
ARIZONA                   Dr David Payne 1050 East University Mesa, AZ
                          85203 Contact: Dr David Payne (602) 834-6632
                          OPEN 931112.
CALIFORNIA                Keith Medical Group 6200 Wilshire Boulevard
                          Los Angeles, CA 90048 Contact: Dr Erik
                          Flelschman (213) 964-1440 OPEN 940210.
CALIFORNIA                Century City Medical Group 2080 Century Park
                          East Suite 710 Century City, CA 90067
                          Contact: Dr Barry Chadsey (310) 201-0900 OPEN
                          940627.
CALIFORNIA                Dr Richard Kuritzkes 2701 West Alameda Avenue
                          / Suite 308 Burbank, CA 91505 Contact: Dr
                          Richard Kuritzkes (818) 845-3773 OPEN 940210.
CALIFORNIA                University of California / San Diego
                          Treatment Center 2760 Fifth Avenue / Suite
                          300 San Diego, CA 92103 Contact: Cathy Nuffer
                          (619) 543-8080 Contact: Dr Diane Havir (619)
                          543-8080 OPEN 930111.
CALIFORNIA                Westside Neighborhood Medical Clinic 628 West
                          Micheltorena Santa Barbara, CA 93101 Contact:
                          Dr Jeffrey Syme OPEN 930111.
CALIFORNIA                Dr William Koonce 219 Nogales Drive Santa
                          Barbara, CA 93105 Contact: Dr William Koonce
                          (805) 682-7200 OPEN 940210.
CALIFORNIA                San Francisco General Hospital 1001 Porero
                          Avenue San Francisco, CA 94110 Contact: Dr
                          Donald Abrams (415) 476-4082 OPEN 940627.
CALIFORNIA                Kaiser Permanente 2200 O'Farrell Street San
                          Francisco, CA 94115 Contact: Dr Stanley Hill
                          (415) 202-2220 OPEN 940210.
CALIFORNIA                Dr Robert Scott 368 28th Street Oakland, CA
                          94609 Contact: Dr Robert Scott (510) 834-1950
                          OPEN 940811.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue /
                          Suite 235 Berkeley, CA 94705 Contact: Sherry
                          Lyman (510) 204-1870 Contact: Dr Carol
                          Brosgart (510) 204-1201 OPEN 930111.
CALIFORNIA                Joaquin County General Hospital 500 West
                          Hospital Road French Camp, CA 95231 Contact:
                          Dr Rod Felber (209) 468-6026 OPEN 940210.
COLORADO                  Childrens Hospital / Division of Pediatrics
                          B-055 1056 East 19th Avenue Denver, CO 80218
                          Contact: Dr Betsy McFarland (303) 861-6981
                          OPEN 930111.
DISTRICT OF COLUMBIA      Dr Larry Lyle 801 Pennsylvania Avenue
                          Southeast Washington, DC 20003 Contact: Dr
                          Larry Lyle (202) 546-0796 OPEN 940627.
DISTRICT OF COLUMBIA      Dr Douglas Ward 1737 20th Street Northwest
                          Washington, DC 20009 Contact: Dr Douglas Ward
                          (202) 745-0201 OPEN 940627.
FLORIDA                   Dr Goodgame and Hopkins 340 N Maitland Avenue
                          Maitland, FL 32751 Contact: Chuck DeMarzo
                          (407) 647-6000 OPEN 931112.
FLORIDA                   Dr Rita Poblete 901 NW Seventeenth Street /
                          Suite D Miami, FL 33136 Contact: Dr Rita
                          Poblete (305) 548-4598 OPEN 940505.
FLORIDA                   University of Miami School of Medicine 1550
                          Northwest Tenth Avenue Room 201 Miami, FL
                          33136 Contact: Dr Della Rivera (305) 547-6676
                          OPEN 940627.
FLORIDA                   Dr Larry Wardzala 1301 East Broward Boulevard
                          / Suite 303 Ft Lauderdale, FL 33301 Contact:
                          Dr Larry Wardzala (305) 463-4602 OPEN 940210.
FLORIDA                   Dr Tom Wazny 2885 Tamiami Trail Port
                          Charlotte, FL 33952 Contact: Dr Tom Wazny
                          (813) 624-7230 OPEN 930111.
GEORGIA                   Medical College of Georgia Infectious
                          Diseases Building AF-2013 Augusta, GA 30912
                          Contact: John Fisher (706) 721-2236 OPEN
                          940505.
ILLINOIS                  Dr Richard MacDonald 990 West Fullerton /
                          Suite 495 Chicago, IL 60614 Contact: Dr
                          Richard MacDonald (312) 525-7171 OPEN 930111.
ILLINOIS                  Dr David Blatt 906 West Belmont Chicago, IL
                          60657 Contact: Dr David Blatt (312) 929-0808
                          OPEN 930111.
ILLINOIS                  Dr Daniel Berger 2835 North Sheffield / Suite
                          104 Chicago, IL 60657 Contact: Dr Daniel
                          Berger (312) 296-2400 OPEN 940210.
LOUISIANA                 Browne - Mchardy Clinic 4315 Houma Boulevard
                          Metairle, LA 70006 Contact: Dr Frank Rabito
                          (504) 889-5367 OPEN 940404.
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue
                          Boston, MA 02215 Contact: Dr Judith Currier
                          OPEN 930111.
MASSACHUSETTS             Harvard Community Health One Fenway Plaza
                          Boston, MA 02215 Contact: Dr Calvin Cohen
                          (617) 421-5846 OPEN 940811.
MARYLAND                  Dr Michael Levin 4000 Old Court Rd / Suite
                          301 Pikeville, MD 21208 Contact: Dr Michael
                          Levin (410) 486-5991 OPEN 940404.
MISSISSIPPI               University of Mississippi / Department of
                          Medicine 2500 North State Street Jackson, MS
                          39216 Contact: Dr Rathel Nolan (601) 984-5556
                          OPEN 940210.
NEBRASKA                  University of Nebraska Medical Center 6000
                          South 42nd Street Omaha, NE 68198-5130
                          Contact: Dr Susan Swindells (402) 559-8201
                          OPEN 940210.
NEW HAMPSHIRE             Manchester Veterans Administration Medical
                          Center 718 Smyth Road Manchester, NH 03104
                          Contact: Dr Donald Bernard (603) 624-4366
                          OPEN 931112.
NEW JERSEY                Dr Nina Regevik 530 New Brunswick Avenue
                          Perth Amboy, NJ 08861 Contact: Dr Nina
                          Regevik (908) 324-5022 OPEN 940627.
NEVADA                    Dr Kathryn Crooks 2810 West Charleston
                          Boulevard / Quall Park IV / Bldg F-54 Las
                          Vegas, NV 89102 Contact: Dr Kathryn Crooks
                          (702) 870-0808 OPEN 940210.
NEVADA                    University Medical Center 1800 West
                          Charleston Las Vegas, NV 89102 Contact: Dr
                          Jerry Cade (702) 877-8600 OPEN 940811.
NEW YORK                  Dr Howard A Grossman 285 West 11th Street /
                          Suite 1-W New York, NY 10014 Contact: George
                          Theodore (212) 929-2629 OPEN 940210.
NEW YORK                  Dr Jeffrey Green 345 East 37th Street / Suite
                          208 New York, NY 10016 Contact: Dr Jeffrey
                          Green (212) 682-2844 OPEN 940210.
NEW YORK                  The New York Hospital / Cornell Med Ctr /
                          Dept of Medicine 1300 New York Avenue / Room
                          A-421 New York, NY 10021 Contact: Dr Rosemary
                          Soave (212) 746-6320 OPEN 930111.
NEW YORK                  New York Med College / Pediatric Dept Munger
                          Pavilion Valhalla, NY 10595 Contact: Dr Oya
                          Tugal (914) 285-7997 OPEN 930111.
NEW YORK                  State U of New York / Hlth Science Center /
                          Dept of Peds 450 Clarkson Avenue / Box 49
                          Brooklyn, NY 11203 Contact: Dr Margaret
                          Hammerschlag (718) 245-4074 OPEN 930111.
NEW YORK                  City Hospital Center 79-01 Broadway Elmhurst,
                          NY 11373 Contact: Dr George Alonso (718)
                          334-3969 OPEN 940505.
OKLAHOMA                  Associates in Medical and Mental Health 1560
                          East 21st Street / Suite 210 Tulsa, OK
                          74114-1325 Contact: Virginia Butler (918)
                          743-1000 OPEN 940210.
PENNSYLVANIA              Childrens Hospital of Philadelphia / Division
                          of General Ped 34th Street and Civic Center
                          Boulevard / 2nd Floor Room 2015 Philadelphia,
                          PA 19104 Contact: Dr Richard Rutstein (215)
                          590-1466 OPEN 940404.
 
140
UNIQUE IDENTIFIER         FDA/00474
PROTOCOL ID NUMBERS       FDA 058I
PROTOCOL TITLE            A Double-Blind, Placebo-Controlled, Parallel
                          Group, Multicenter Study of Azithromycin as
                          Prophylaxis Against the Development of
                          Mycobacterium avium Complex Disease in
                          HIV-Infected People.
VERSION NUMBER & DATE     (920903)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy and safety
                          of azithromycin administered once a week in
                          the prevention of disseminated Mycobacterium
                          avium Complex (MAC) in severely
                          immunocompromised HIV-infected patients with
                          a CD4 count < 100 cells/mm3.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920821)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection confirmed by
                          ELISA with Western blot or polymerase chain
                          reaction (PCR). 2. CD4 count < 100 cells/mm3.
                          3. No MAC positive blood cultures within 1
                          month prior to study entry (patients with
                          stool cultures positive for MAC may enter the
                          study provided at least two blood cultures
                          are negative). 4. Absence of symptoms
                          suggestive of disseminated MAC infection
                          (including unexplained diarrhea, fever, and
                          night sweats) within 1 month of study entry.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    066-155
STUDY DESIGN              Double-Blind; Placebo-Controlled;
                          Multicenter; Parallel-Group
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug prophylaxis.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. CD4 count < 100
                          cells/mm3. 3. No MAC positive blood cultures
                          within 1 month prior to study entry. 4. No
                          symptoms suggestive of disseminated MAC
                          infection (including unexplained diarrhea,
                          fever, and night sweats) within 1 month of
                          study entry. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 100 cells/mm3. ( 0 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 2.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 1000 cells/mm3. BUN < 30
                          mg/dl. Alkaline phosphatase <= 5 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required:
                          Anti-pneumocystis prophylactic therapy
                          (dihydropteroate synthetase inhibitors with
                          or without dihydrofolate reductase
                          inhibitors, pentamidine). Allowed:
                          Concomitant anti-HIV therapy (AZT, ddI, ddC)
                          or antifungal therapy (including azoles).
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of MAC or Mycobacterium tuberculosis
                          (MTb) infection. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within the past 4
                          weeks: Any putative anti-MAC therapies
                          including rifampin, rifabutin, clofazimine,
                          ethambutol, cycloserine, ethionamide,
                          amikacin, and ciprofloxacin or other
                          quinolones thought to be active against MAC.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          investigational new drugs (except for
                          foscarnet or ddC) unless prior agreement has
                          been reached between the investigator and the
                          Pfizer project physician. 2. Concomitant
                          putative immunostimulants.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Positive PPD within 3 months prior to study
                          entry (negative PPD defined as < 5 mm
                          induration). 2. Chest x-ray suggestive of any
                          active disease, in particular tuberculosis.
                          3. Known hypersensitivity to macrolide
                          antibiotics. 4. Any other acute clinical
                          condition likely to interfere with completion
                          of the protocol. 5. Inability to care for
                          self without considerable assistance and
                          medical care.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUPPORTING AGENCY         Pfizer Incorporated.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*PREVENTION & CONTROL
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        920821
ENTRY MONTH               9211
CALIFORNIA                Naval Hospital Infectious Diseases Division
                          San Diego, CA 92134-5000 Contact: Dr Edward
                          Oldfield III (619) 532-7475 OPEN 921117.
NORTH CAROLINA            Womack Army Medical Center Medical Clinic
                          Fort Bragg, NC 28307-5000 Contact: Dr Richard
                          Williams (910) 432-6028 OPEN 921117.
 
141
UNIQUE IDENTIFIER         FDA/00473
PROTOCOL ID NUMBERS       FDA 058H
PROTOCOL TITLE            An Open, Multicenter, Randomized,
                          Dose-Ranging Study of Azithromycin in the
                          Treatment of Disseminated Mycobacterium
                          avium-intracellulare Complex Infection (MAC)
                          in Patients with Acquired Immune Deficiency
                          Syndrome (AIDS).
VERSION NUMBER & DATE     (920901)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy and safety
                          of two doses of azithromycin given
                          chronically for the treatment of
                          Mycobacterium avium bacteremia in AIDS
                          patients.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920821)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA and confirmed by Western blot. 2.
                          Disseminated Mycobacterium avium Complex
                          infection defined by a positive blood culture
                          for MAC within 1 month prior to study entry.
                          3. Fever (> 100 degrees F) that cannot be
                          attributed to another active infection, and
                          at least one other constitutional symptom
                          (such as fatigue, malaise, anorexia).
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-148
STUDY DESIGN              Open Label; Multicenter; Randomized; Dose
                          Ranging
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 6 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Disseminated
                          Mycobacterium avium Complex. 3. Fever (> 100
                          degrees F) that cannot be attributed to
                          another active infection, and at least one
                          other constitutional symptom (such as
                          fatigue, malaise, anorexia). 4. Life
                          expectancy of at least the duration of the
                          study. 5. Consent of parent or guardian if
                          below the legal age of consent. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: > 7 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: < 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Neutrophils > 500 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Abstinence or effective
                          method of birth control / contraception
                          during the study and for 90 days after.
OTHER PATIENT INCL. CH.   WEIGHT: >= 40 kg
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Medications
                          allowed under a Treatment IND program.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 90 days after.
PATIENT EXCLUSION CRIT.   WEIGHT: < 40 kg
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Not expected to comply with
                          the requirements of the protocol, in the
                          opinion of the investigator.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Treatment with
                          an immunostimulant or immunomodulator
                          compound such as alpha-interferon,
                          gamma-interferon, or any interleukin within 7
                          days prior to study entry. 2. Any other
                          antibiotic with known activity against M.
                          avium within 7 days prior to study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Known hypersensitivity or significant
                          intolerance to macrolide antibiotics. 2.
                          Inability to take oral medications or a
                          current condition likely to interfere with
                          drug absorption (e.g., gastrectomy).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUPPORTING AGENCY         Pfizer Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        920821
ENTRY MONTH               9211
MASSACHUSETTS             Beth Israel Hospital 330 Brookline Avenue /
                          LY-124 Boston, MA 02215 Contact: Dr Judith
                          Currier (617) 735-4700 OPEN 921105.
NEW YORK                  Bronx Veterans Affairs Medical Center / Div
                          Infec Diseases 130 West Kingsbridge Road
                          Bronx, NY 10468 Contact: Dr Jeffrey Jacobson
                          (718) 584-9000 X 116OPEN 921105.
NEW YORK                  SUNY / Upstate Medical Center 750 East Adams
                          Street Syracuse, NY 13210 Contact: Dr Michael
                          Cynamon (315) 464-5533 OPEN 921105.
OHIO                      Ohio State University Hospitals N-1135 Doan
                          Hall 410 West 10th Avenue Columbus, OH 43210
                          Contact: Dr Susan Koletar (614) 293-8745 OPEN
                          921105.
 
142
UNIQUE IDENTIFIER         FDA/00429
PROTOCOL ID NUMBERS       FDA 058F
PROTOCOL TITLE            Azithromycin in the Treatment of
                          Cryptosporidiosis in Patients With Acquired
                          Immune Deficiency Syndrome (AIDS): A
                          Randomized, Multi-Center, Placebo-Controlled,
                          Double-Blind Study.
VERSION NUMBER & DATE     (910712)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the safety and efficacy
                          of azithromycin in the treatment of
                          intestinal cryptosporidial infection in AIDS
                          patients.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920706)
DISEASE STUDIED           Cryptosporidiosis / diarrhea.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection. 2. Intestinal
                          cryptosporidiosis proven by stool microscopy
                          on at least two occasions prior to study
                          enrollment.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-143
STUDY DESIGN              Randomized; Multicenter; Placebo-Controlled;
                          Double-Blind
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. Intestinal
                          cryptosporidiosis proven by stool microscopy
                          on at least two occasions prior to study
                          enrollment. 3. Life expectancy of at least 2
                          weeks by clinical assessment. In states where
                          the legal age of consent for medical
                          procedures is 21 years, patients below the
                          age of 21 must have consent of parent or
                          guardian. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 7 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 40 ml/min.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 5 x ULN.
                          Absolute neutrophil count (mature PMNs and
                          Bands only) >= 500 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          during the study and for 30 days after.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Zidovudine.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1.
                          Zidovudine. 2. Antidiarrheal medication with
                          immodium or paragoric only.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control
                          during study and for 30 days after.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Not expected to comply with
                          the requirements of the protocol, in the
                          opinion of the investigator.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Another
                          investigational drug within 7 days prior to
                          study enrollment (investigational medications
                          available through a treatment IND will be
                          allowed with the approval of the sponsor, the
                          treatment IND sponsor, and the Pfizer
                          clinical monitor). 2. Immunostimulant or
                          lymphocyte replacement therapy. 3. Cancer
                          chemotherapy (including therapy for Kaposi's
                          sarcoma).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Cancer
                          chemotherapy (including therapy for Kaposi's
                          sarcoma). 2. Any drug or biologic preparation
                          (e.g., bovine colostrum, paromomycin,
                          spiramycin, somatostatin) with possible
                          anticryptosporidial activity. 3.
                          Immunostimulant or lymphocyte replacement
                          therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Known hypersensitivity or significant
                          intolerance to macrolide antibiotics. 2.
                          Marked abnormalities of liver or renal
                          function. 3. Causes for diarrhea other than,
                          or in addition to, cryptosporidiosis. 4.
                          Inability to receive oral medication.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
TRADE NAME OF SUBSTANCE   Drug 1 CP-62,933
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUPPORTING AGENCY         Pfizer Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/*THERAPEUTIC USE
MESH HEADING              Cryptosporidiosis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        920706
ENTRY MONTH               9207
CALIFORNIA                University of California at San Diego Medical
                          Center 225 Dickenson Street Suite 8208 San
                          Diego, CA 92103 Contact: Dr Diane Havlir
                          (619) 792-7675 OPEN 920706.
CALIFORNIA                Infectious Disease Medical Group 350 30th
                          Street / Suite 511 Oakland, CA 94609 Contact:
                          Dr Patrick Joseph (510) 273-8200 Contact:
                          Bruce Ross (510) 273-8200 OPEN 920706.
NEW YORK                  Cornell University Medical Center 525 East
                          68th Street / Room 2434 New York, NY 10021
                          Contact: Brenda Greenhill (212) 746-4177 OPEN
                          920706 ACTU: 2201.
 
143
UNIQUE IDENTIFIER         FDA/00438
PROTOCOL ID NUMBERS       FDA 058D
PROTOCOL TITLE            A Study to Evaluate the Safety and Efficacy
                          of Azithromycin in Individual Patients With
                          Serious Nontuberculous Mycobacterial Disease
                          Who Are Failing or Intolerant of Other
                          Available Therapy.
VERSION NUMBER & DATE     2 (910927)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
TRIAL CATEGORY            Nationwide Access
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy and safety
                          of azithromycin given chronically for the
                          treatment of serious nontuberculous
                          mycobacterial infection in patients failing
                          or intolerant of other available therapy.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920821)
DISEASE STUDIED           Nontuberculous mycobacterial infection,
                          Mycobacterium avium-intracellulare infection
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Serious nontuberculous
                          mycobacterial disease defined as disabling or
                          life-threatening infection that may be
                          localized or disseminated. 2. Mycobacterial
                          species has been identified as sensitive to
                          azithromycin, either in vitro or by known in
                          vivo animal or human data. 3. Has been
                          treated for at least 6 weeks and has not
                          responded to more conventional therapy for
                          this infection, OR initially responded and
                          has experienced recurrence or worsening of
                          infection on therapy, OR cannot tolerate
                          continued conventional therapy.
ELIGIBILITY               AIDS. OTHER.
OTHER PROTOCOL NUMBERS    066-169
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Compassionate use.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 2 units.
INPATIENT/OUTPATIENT ST.  Inpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Serious nontuberculous mycobacterial
                          infection. 2. Approval of eligibility from
                          Pfizer Clinical Monitor. Patients below the
                          legal age of consent must have consent of
                          parent or guardian. NOTE: Pregnant women,
                          women of childbearing potential, and children
                          will not be specifically excluded from
                          participation. However, patients and
                          physicians should be aware that the safety of
                          azithromycin during pregnancy and in
                          long-term use in children and adults has not
                          been established. The risks and benefits of
                          azithromycin use in these patients will be
                          considered in consultation with the physician
                          and the Pfizer Clinical Monitor. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT AGE               AGE: 01 Days - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Other
                          antimicrobial drugs as long as documented on
                          Case Report Form.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hypersensitivity or intolerance to
                          azithromycin. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Disseminated Mycobacterium avium complex
                          (MAC) who are eligible for treatment with
                          azithromycin under protocol 066-162. 2. Known
                          hypersensitivity or intolerance to macrolide
                          antibiotics.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
TRADE NAME OF SUBSTANCE   Drug 1 CP-62,993
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUPPORTING AGENCY         Pfizer Central Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/*THERAPEUTIC USE
MESH HEADING              Child
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium Infections, Atypical/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        920821
ENTRY MONTH               9209
CONNECTICUT               Pfizer Central Research / USA Accrual Eastern
                          Point Rd Groton, CT 06340 Contact: Dr Debra
                          Williams (203) 441-5463 OPEN 921001.
MARYLAND                  NIH / NCI / Metabolism Branch Room 4N-115 /
                          Building 10 / 9000 Rockville Pike Bethesda,
                          MD 20892 Contact: Dr David Nelson (301)
                          496-3024 CLOSED 940915.
 
144
UNIQUE IDENTIFIER         FDA/00472
PROTOCOL ID NUMBERS       FDA 058C
PROTOCOL TITLE            An Open-Label Study of the Use of
                          Azithromycin in Patients With Symptomatic
                          Disseminated Mycobacterium
                          avium-intracellulare Complex (MAC) Infection
                          Failing Current Therapy.
VERSION NUMBER & DATE     2 (910927)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Child
GENERAL DESCRIPTION       PURPOSE: To evaluate the efficacy and safety
                          of azithromycin given chronically for the
                          treatment of Mycobacterium avium (MAC)
                          bacteremia in patients failing or intolerant
                          of current available MAC therapy.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (920822)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Disseminated MAC as defined by
                          current (within the last month) positive
                          blood, bone marrow, or liver biopsy culture
                          for MAC, and considered symptomatic (fever,
                          night sweats, anorexia, weight loss, fatigue,
                          or malaise). 2. At least 2 months of prior
                          treatment with available combination MAC
                          therapy or less than 2 months of such
                          accompanied by unacceptable adverse effects.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-162
STUDY DESIGN              Open Label
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 44 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Disseminated MAC as defined by
                          current (within the last month) positive
                          blood, bone marrow, or liver biopsy culture
                          for MAC, and considered symptomatic (fever,
                          night sweats, anorexia, weight loss, fatigue,
                          or malaise). 2. At least 2 months of prior
                          treatment with available combination MAC
                          therapy or less than 2 months of such
                          accompanied by unacceptable adverse effects.
                          3. Life expectancy of more than 2 weeks. 4.
                          Approval of eligibility from Pfizer Clinical
                          Monitor. 5. Consent of parent or guardian if
                          under legal age of consent. NOTE: Patients
                          who have completed acute treatment with
                          azithromycin for MAC in protocol 066-131 or
                          066-148 will be exempt from inclusion
                          criteria 1 and 2 and can continue therapy
                          through this protocol if their physician
                          feels they have benefitted from prior
                          azithromycin therapy. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3.0 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT AGE               AGE: 01 Days - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hypersensitivity or intolerance to
                          azithromycin. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Other
                          investigational drugs within 7 days of
                          enrollment, with the exception of Treatment
                          IND drugs (such as ddC).
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other MAC
                          therapy instituted during the first 2 months
                          of the study. 2. Other investigational drugs,
                          with the exception of those available through
                          a Treatment IND program.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms and conditions are excluded: 1.
                          Known hypersensitivity or intolerance to
                          macrolide antibiotics. 2. Inability to take
                          oral medications or current condition that is
                          likely to interfere with absorption (e.g.,
                          gastrectomy).
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUPPORTING AGENCY         Pfizer Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Child
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        920822
ENTRY MONTH               9211
ALABAMA                   Dr John Dunkel 101-A Bob Wallace Avenue
                          Huntsville, AL 35801 Contact: Dr John Dunkel
                          (205) 533-6558 OPEN 921105.
ARIZONA                   University of Arizona 1609 North Warren
                          Street / Room 121 Tucson, AZ 85719 Contact:
                          Dr Kevin Carmichael (602) 626-6967 OPEN
                          921105.
CALIFORNIA                University of California San Diego / Medical
                          Center 225 Dickenson Street / Mail Code 8451
                          San Diego, CA 92103 Contact: Dr Wayne Danker
                          (619) 543-2744 OPEN 921105.
CALIFORNIA                Fountain Valley Regional Hospital and Medical
                          Center 17150 Euclid Avenue / Suite 322
                          Fountain Valley, CA 92708 Contact: Dr Douglas
                          Cable (714) 432-0422 OPEN 921105.
CALIFORNIA                Devlin Peterson Clinic 513 West Columbus /
                          Suite A Bakersfield, CA 93303-2824 Contact:
                          Patrick Nemechek (805) 633-1242 OPEN 921105.
CALIFORNIA                Dr David Leece 1235 Osos Street San Luis
                          Obispo, CA 93401 Contact: Dr David Leece
                          (805) 546-5630 OPEN 921105.
CALIFORNIA                District Health Center No 1 3850 17th Street
                          San Francisco, CA 94114 Contact: Fred Strauss
                          (415) 554-9750 OPEN 921105.
CALIFORNIA                Davies Medical Center 45 Castro Street /
                          Suite 402 San Francisco, CA 94114 Contact: Dr
                          William Owen (415) 861-2400 OPEN 921105.
CALIFORNIA                Dr Jacob Lalezari 2300 Sutter Street / Suite
                          202 San Francisco, CA 94115 Contact: Dr Jacob
                          Lalezari (415) 476-6356 OPEN 921105.
CALIFORNIA                Kuzell Institute / Division of Infectious
                          Diseases 2200 Webster Street San Francisco,
                          CA 94115-1896 Contact: Dr Lowell Young (415)
                          923-3262 OPEN 921105.
CALIFORNIA                Infectious Disease Medical Group 350 30th
                          Street / Suite 511 Oakland, CA 94609 Contact:
                          Dr Patrick Joseph (510) 834-2800 OPEN 921105.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue /
                          Suite 235 Berkeley, CA 94705 Contact: Sherry
                          Lyman (510) 204-1870 Contact: Dr Carol
                          Brosgart (510) 204-1201 OPEN 921105.
CALIFORNIA                Medical Group of Watsonville 850 Freedom
                          Boulevard Watsonville, CA 95076 Contact: Dr
                          Thomas Deetz (408) 724-2211 OPEN 921105.
COLORADO                  Fitzsimmons Army Medical Center / Infectious
                          Diseases Clinic P O Box 6295 Aurora, CO 80045
                          Contact: Dr William Byrne OPEN 921105.
COLORADO                  Infectious Disease 2045 Franklin Street
                          Denver, CO 80205-5494 Contact: Dr Miguel
                          Mogyoros (303) 861-3652 OPEN 921105.
CONNECTICUT               Danbury Newton Road Newton, CT 06470 Contact:
                          Dr Donald Evans (203) 426-5626 OPEN 921105.
CONNECTICUT               Yale University School of Med / Department of
                          Internal Med P O Box 3333 New Haven, CT
                          06510-8056 Contact: Unspecified (203)
                          737-4040 OPEN 921105.
FLORIDA                   Wuestoff Hospital 110 Longwood Avenue
                          Rockledge, FL 32956-5002 Contact: Dr Mary
                          Ulrich (407) 636-2211 OPEN 921105.
GEORGIA                   Dr Richard Hudson 155 North Avenue Atlanta,
                          GA 30308 Contact: Dr Richard Hudson OPEN
                          921105.
GEORGIA                   Geogia Baptist Hospital / Atlanta Medical
                          Associates 100 10th Street Northwest Atlanta,
                          GA 30309 Contact: Dr Dennis Melton (404)
                          897-6836 OPEN 921105.
INDIANA                   Dr Karen Isreal 1633 North Capitol Avenue /
                          Suite 550 Indianapolis, IN 46202 Contact: Dr
                          Karen Isreal (317) 929-2424 OPEN 921105.
INDIANA                   Wishard Memorial Hospital OPW430 1001 West
                          10th Street Indianapolis, IN 46202-2879
                          Contact: Dr L Joseph Wheat (317) 630-6262
                          OPEN 921105.
LOUISIANA                 Tulane Medical Center / Infectious Diseases
                          150 South Liberty St / Columbia Bldg / Third
                          Floor New Orleans, LA 70112 Contact: Dr David
                          Mushat (504) 587-7316 OPEN 921105.
MASSACHUSETTS             University of Massachussetts Medical Center
                          55 Lake Avenue North Worcester, MA 01655
                          Contact: Dr Patrick Fairchild (508) 856-4261
                          CLOSED 930604.
MASSACHUSETTS             Boston City Hospital / Department of
                          Pediatrics Boston, MA 02118 Contact: Dr
                          Jo-Ann Harris (617) 534-5802 OPEN 921105.
MASSACHUSETTS             Beth Israel Hospital LY-124 330 Brookline
                          Avenue Boston, MA 02215 Contact: Dr Judith
                          Currier (617) 735-4700 OPEN 921105.
MARYLAND                  Dr Michael Levin 4000 Old Court Road / Suite
                          301 Pikesville, MD 21208 Contact: Dr Michael
                          Levin (410) 486-5991 OPEN 921105.
MARYLAND                  Dr Raymond Altieri 314 German HIll Road
                          Dundalk, MD 21222 Contact: Dr Raymond Altieri
                          (410) 323-2500 OPEN 921105.
NEW HAMPSHIRE             Dartmouth-Hitchcock Medical Center / Sect of
                          Infect Diseases Lebanon, NH 03756 Contact: Dr
                          Charles Von Reyn OPEN 921105.
NEW JERSEY                Dr Jeffrey Kocher 130 Broad Avenue Leonia, NJ
                          07631 Contact: Dr Jeffrey Kocher OPEN 921105
                          ACTU: 000F.
NEW YORK                  Cabrini Medical Center 227 East 19th Street
                          New York, NY 10003 Contact: Dr John Montana
                          (212) 505-7730 OPEN 921105.
NEW YORK                  Bellevue Hospital Center AIDS Program First
                          Avenue at 27th Street / Room 12 East 12 New
                          York, NY 10016 Contact: Dr Mary Vogler (212)
                          561-3906 Contact: (212) 561-4038 OPEN 921105.
NEW YORK                  Department of Veterans Affairs / Division of
                          Infectious Dis 130 West Kingsbridge Road
                          Bronx, NY 10468 Contact: Dr Jeffrey Jacobson
                          (718) 584-9000 OPEN 921105.
NEW YORK                  Office of Dr Thomas Rush 141 North State Road
                          Briarcliff Manor, NY 10510 Contact: Dr Thomas
                          Rush (914) 762-2276 OPEN 921105.
NEW YORK                  State University of New York Health Science
                          Center 750 East Adams Street Syracuse, NY
                          13210 Contact: Dr Michael Cynamon (315)
                          464-5533 OPEN 921105.
NEW YORK                  United Health Services Binghamton, NY 13903
                          Contact: Dr Barbara Chaffee (607) 722-9081
                          OPEN 921105.
NEW YORK                  University of Rochester / Department of
                          Infect Dis Bos 689 Rochester, NY 14642
                          Contact: Dr Amy Portmore OPEN 921105.
OHIO                      Ohio State University Hospitals N-1135 Doan
                          Hall / 410 West Tenth Avenue Columbus, OH
                          43210 Contact: Dr Susan Koletar (614)
                          293-8745 OPEN 921105.
OHIO                      Doan Hall N-1144 410 West Tenth Avenue
                          Columbus, OH 43210-1228 Contact: Dr Robert
                          Fass (614) 293-8732 OPEN 921105.
OHIO                      Principal Health Care of Ohio 4885 Olentangy
                          River Road Columbus, OH 43214 Contact: Dr
                          Vincent Spagna (614) 451-1551 OPEN 921105.
 
145
UNIQUE IDENTIFIER         FDA/00148
PROTOCOL ID NUMBERS       FDA 058A
PROTOCOL TITLE            Study of Azithromycin in the Treatment of
                          Toxoplasmic Encephalitis in AIDS Patients Who
                          Cannot be Treated with Conventional Therapy.
VERSION NUMBER & DATE     (901204)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: The primary purpose of this protocol
                          is to provide azithromycin for the treatment
                          of individual patients who require therapy
                          for toxoplasmic encephalitis and who cannot
                          receive conventional therapies due to prior
                          clinical failure or significant intolerance.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940210)
DISEASE STUDIED           Toxoplasmic encephalitis.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. A diagnosis of toxoplasmic
                          encephalitis in patients with AIDS
                          established by: a) Demonstration of the
                          organism in cerebrospinal fluid or material
                          obtained at brain biopsy or aspiration of a
                          brain abscess. OR b) Lesions detected by
                          computed tomography or by nuclear magnetic
                          resonance studies characteristic of those
                          described associated with toxoplasmic
                          encephalitis in patients with AIDS but in
                          whom: 1) The decision has been made that the
                          lesions are that make surgical intervention
                          inadvisable or surgical intervention is
                          refused by the patient or is inadvisable for
                          reasons of the patients clinical status or
                          other circumstance. AND 2) Prior specific
                          antitoxoplasmic therapy must have shown some
                          favorable clinical response in cases where
                          the diagnosis of toxoplasmic encephalitis is
                          presumptive (has not been proven by
                          identification of the organism from brain
                          tissue). 2. A minimum life expectancy of one
                          week. 3. Must have failed or been intolerant
                          to prior therapy with sulfa drugs or
                          pyrimethamine.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    066-133
PROTOCOL DETAILS          STUDY INTENT: Drug therapy, Compassionate
                          use.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 23 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have the following: o A diagnosis of
                          toxoplasmic encephalitis in patients with
                          AIDS. o Baseline history, physical
                          examination, and clinical laboratory tests. o
                          Given written informed consent prior to
                          his/her inclusion in the study. NOTE:
                          Patients below the age of legal consent will
                          have, in addition to the above consent,
                          written permission and informed consent from
                          a parent or guardian. The final judgement of
                          patient acceptability for inclusion lies with
                          the Pfizer Clinical Monitor. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Therapeutic
                          failure with or intolerance to prior therapy
                          with sulfa drugs or pyrimethamine.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following are excluded: Known sensitivity to
                          macrolide antibiotics. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions or symptoms are excluded: Known
                          sensitivity to macrolide antibiotics.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0104  Azithromycin
TRADE NAME OF SUBSTANCE   Drug 1 Azithromycin
MANUFACTURERS             Drug 1: Pfizer Incorporated Eastern Point
                          Road / Central Research Groton, CT 06340
                          Contact: Robert Myers (203) 441-3817.
SUPPORTING AGENCY         Pfizer, Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Azithromycin/*THERAPEUTIC USE
MESH HEADING              Drug Evaluation
MESH HEADING              Encephalitis/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Toxoplasmosis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       83905-01-5 (Azithromycin)
LAST REVISION DATE        940210
ENTRY MONTH               9102
CALIFORNIA                University of California Medical Center 225
                          Dickinson Street / Owen Clinic H-881 San
                          Diego, CA 92103-1990 Contact: Dr Christopher
                          Matthews (619) 294-3767 OPEN.
CALIFORNIA                Kern Medical Center 1830 Flower Street
                          Bakersfield, CA 93305 Contact: Patrick
                          Nemechek D O (805) 326-3000 OPEN 911021.
CALIFORNIA                The Permanente Medical Group Inc 2200
                          O'Farrell Street San Francisco, CA 94115-3394
                          Contact: Dr Jeffrey Fessell (415) 929-4848
                          OPEN.
CALIFORNIA                Pacific Presbyterian Medical Center PO Box
                          7999 Clay at Buchanan Street San Francisco,
                          CA 94120 Contact: Dr Lory Wiviott (415)
                          563-4321 OPEN.
CALIFORNIA                Scott Eberle M D 2403 Professional Drive /
                          Suite 104 Santa Rosa, CA 95401 Contact: Dr
                          Scott Eberle (707) 544-3340 OPEN 911021.
CALIFORNIA                University of California Davis / School of
                          Medicine Med Ctr 2221 Stockton Boulevard
                          Sacramento, CA 95817 Contact: Dr Neil Flynn
                          (916) 734-2011 OPEN.
FLORIDA                   South Miami Hospital 7000 Southwest 62nd
                          Avenue Suite 650 Miami, FL 33143 Contact: Dr
                          Paula Sparti (305) 661-1150 OPEN.
ILLINOIS                  Saint Anthony's Medical Center 5666 East
                          State Avenue Rockford, IL 61108-2472 Contact:
                          Dr Scott Homan (815) 226-2000 OPEN.
INDIANA                   Infectious Disease of Indianapolis PSC 1633
                          North Capitol Suite 700 Indianapolis, IN
                          46202 Contact: Dr John Black (317) 929-2700
                          OPEN.
LOUISIANA                 Irwin Trestman M D 4224 Houma Boulevard /
                          Suite 360 Metairie, LA 70006 Contact: Dr
                          Irwin Trestman (504) 456-5144 OPEN 911021.
MICHIGAN                  Dr Paul Benson 2327 Coolidge Berkley, MI
                          48072 Contact: David Rock (810) 544-9300 OPEN
                          940210.
MICHIGAN                  Hutzel Hospital 4707 St Antoine Boulevard
                          Detroit, MI 48201 Contact: Theodore Benjamin
                          Jones (313) 745-7269 OPEN ACTU: 1701.
NEW JERSEY                Leonia Medical Associates P A 130 Broad
                          Avenue Leonia, NJ 07605 Contact: Dr Jeffrey
                          Kocher (201) 944-6612 OPEN 911021.
NEW YORK                  Cabrini Medical Center 227 East 19th Street
                          New York, NY 10003 Contact: Dr Michael Mullen
                          (212) 725-7305 Contact: (212) 979-8929 OPEN.
NEW YORK                  Bellevue Hospital First Avenue and 27th
                          Street New York, NY 10016 Contact: Dr Mindell
                          Seidlin (212) 561-3906 OPEN.
NEW YORK                  Barry Hartman M D 407 East 70th Street New
                          York, NY 10021 Contact: Dr Barry Hartman
                          (212) 746-6320 OPEN.
NEW YORK                  New York Hospital / Cornell Med Ctr / Ctr
                          Special Studies 525 East 68th Street / Baker
                          24 New York, NY 10021 Contact: Unspecified
                          (212) 748-4190 OPEN.
NEW YORK                  Mount Sinai Medical Center One Gustave Levy
                          Place New York, NY 10029 Contact: Dr Henry
                          Sacks (212) 241-7856 OPEN.
NEW YORK                  Columbia University 630 West 168th Street New
                          York, NY 10032 Contact: Harold Neu (212)
                          305-3395 OPEN.
NEW YORK                  Hamilton Medical Specialists P C 150 Broad
                          Street Hamilton, NY 13346 Contact: Dr Shelley
                          Gilroy (315) 824-0181 OPEN 911021.
OHIO                      Ohio State University Hospital 410 West Tenth
                          Ave / N 1135 Doan Hall Columbus, OH 43210
                          Contact: Dr Joseph Plouffe (614) 293-8732
                          OPEN 940811.
OREGON                    Oregon Health Sciences University 3181
                          Southwest Sam Jackson Road Portland, OR 97201
                          Contact: Mark Loveless (503) 295-0950 OPEN.
OREGON                    Good Samaritan Hospital and Medical Center
                          1015 Northwest 22nd Avenue Portland, OR 97210
                          Contact: Dr James Sampson (503) 229-8428
                          OPEN.
 
146
UNIQUE IDENTIFIER         FDA/00656
PROTOCOL ID NUMBERS       FDA 048E
PROTOCOL TITLE            An Open-Label Randomized
                          Pharmacokinetic/Pharmacodynamic Study of
                          Mycobutin ( Rifabutin ) or Rifabutin in
                          Combination With Myambutol ( Ethambutol ) for
                          Prophylaxis of Mycobacterium avium Complex (
                          MAC ) Bacteremia in AIDS Patients With CD4
                          Counts <= 100 Cells/mm3.
VERSION NUMBER & DATE     (940811)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To optimize Mycobacterium avium
                          Complex (MAC) prophylaxis in AIDS patients by
                          measuring serum rifabutin levels and
                          adjusting the dose accordingly. To combine
                          rifabutin with ethambutol to examine the
                          effect of combination therapy in preventing
                          or delaying the incidence of MAC bacteremia
                          in this patient population. Methodology:
                          Patients are randomized to receive oral
                          rifabutin alone or rifabutin/ethambutol daily
                          for 12 months, with possible continuation of
                          medicine lifelong. Doses will be adjusted to
                          maintain minimum blood levels of the drugs.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive oral rifabutin alone or
                          rifabutin/ethambutol daily for 12 months,
                          with possible continuation of medicine
                          lifelong. Doses will be adjusted to maintain
                          minimum blood levels of the drugs.
PROTOCOL PHASE            Phase IV
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940810)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS. 2. CD4 count <= 100
                          cells/mm3. 3. NO prior or current MAC
                          infection, and no evidence of disseminated
                          MAC disease on blood culture.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    CS 087287-000
STUDY DESIGN              Open Label; Randomized; Prospective; 2-Arm;
                          Drug Combination; Pharmacokinetic
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Combination
                          and single pharmacokinetics,
                          Pharmacodynamics, Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 200 patients. (100
                          patients on each of two treatment arms)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: At least 12
                          months.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. CD4 count <= 100 cells/mm3.
                          3. NO prior or current MAC infection. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMATOCRIT: >= 25 percent.
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 8 g/dl.
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 100 cells/mm3. ( 0 -
                          100 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2.5 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): < 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): < 5 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 1.5 mg/dl.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase < 3 x ULN.
                          Absolute neutrophils >= 1000 cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or agree to use barrier methods of
                          birth control / contraception during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Antipneumocystis
                          prophylaxis for at least 4 weeks prior to
                          study entry. Allowed: 1. Prior rifabutin. 2.
                          Prior ethambutol. 3. Prior clarithromycin.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: 1. AZT, d4T,
                          ddI, or ddC. 2. Antipneumocystis prophylaxis.
                          Allowed: Short course (< 14 days) of
                          ciprofloxacin for acute infections.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Known hypersensitivity to rifabutin,
                          rifampin, or other rifamycins and/or
                          ethambutol. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use barrier methods of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 4 weeks
                          prior to study entry: 1. Rifampin. 2.
                          Isoniazid. 3. Clofazimine. 4. Cycloserine. 5.
                          Ethionamide. 6. Amikacin. 7. Ciprofloxacin.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Other
                          antiretrovirals not specifically allowed. 2.
                          All investigational drugs. 3. Other
                          antimycobacterial therapy, such as
                          clarithromycin, azithromycin, rifampin,
                          clofazimine, amikacin, streptomycin,
                          isoniazid, cycloserine, ethionamide, and
                          ciprofloxacin (>= 14 days).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Positive tuberculin skin test (PPD > 5 mm).
                          2. Active M. tuberculosis. 3. Perceived as
                          unreliable or unavailable for frequent
                          monitoring.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0085  Rifabutin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0111  Ethambutol
TRADE NAME OF SUBSTANCE   Drug 1 LM 427
TRADE NAME OF SUBSTANCE   Drug 2 Myambutol
MANUFACTURERS             Drug 1: Pharmacia Inc PO Box 16529 Columbus,
                          OH 43216-6529 Contact: Dr James Heusner (614)
                          764-8129.
MANUFACTURERS             Drug 2: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 300 mg daily
                          (starting dose), with adjustment to maintaa
                          minimum blood level of 0.6 mcg/ml rifabutin.
                          Drug 2: 800 mg daily (starting dose), with
                          adjustment to maintaminimum blood level of
                          3-5 mcg/ml ethambutol
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 300 mg. Drug 2: 800 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: At least 12 months.
SUPPORTING AGENCY         Pharmacia Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/*PHARMACOKINETICS/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*PREVENTION & CONTROL
MESH HEADING              Rifabutin/*PHARMACOKINETICS/THERAPEUTIC USE
CAS REGISTRY NUMBER       72559-06-9 (Rifabutin)
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
LAST REVISION DATE        940810
ENTRY MONTH               9409
CALIFORNIA                University of California / Davis Medical
                          Center 2221 Stockton Blvd Sacramento, CA
                          95817 Contact: Dr Neil Flynn (916) 734-3793
                          OPEN 940810.
 
147
UNIQUE IDENTIFIER         FDA/00534
PROTOCOL ID NUMBERS       FDA 048D
PROTOCOL TITLE            A Three-Arm Comparative Trial for the
                          Treatment of MAC Bacteremia in AIDS: A
                          Clarithromycin / Ethambutol Regimen
                          Containing Rifabutin (450 mg) or Rifabutin
                          (300 mg) or Placebo.
VERSION NUMBER & DATE     2 (940419)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To compare the efficacy of
                          clarithromycin/ethambutol with placebo or
                          with rifabutin at two different doses in
                          reducing colony-forming units (CFUs) by 2 or
                          more logarithms in patients with
                          Mycobacterium avium Complex bacteremia and
                          maintaining this response until 16 weeks
                          post-randomization. To assess survival and
                          comparative tolerability among the three
                          treatment regimens. Methodology: Patients are
                          randomized to receive clarithromycin and
                          ethambutol plus either placebo or rifabutin
                          at one of two doses. Treatment continues
                          indefinitely. PER 04/19/94 AMENDMENT: Doses
                          of rifabutin have been changed from 600 and
                          900 mg daily to 300 and 450 mg daily.
                          Patients enrolled prior to the start of the
                          amendment and randomized to either the
                          original 600 or 900 mg dose of rifabutin will
                          begin receiving the 300 mg dose.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive clarithromycin and ethambutol plus
                          either placebo or rifabutin at one of two
                          doses. Treatment continues indefinitely. PER
                          04/19/94 AMENDMENT: Doses of rifabutin have
                          been changed from 600 and 900 mg daily to 300
                          and 450 mg daily. Patients enrolled prior to
                          the start of the amendment and randomized to
                          either the original 600 or 900 mg dose of
                          rifabutin will begin receiving the 300 mg
                          dose.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (930510)
DISEASE STUDIED           Mycobacterium avium-intracellulare infection
                          ( MAI ) ( MAC ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection. 2.
                          Evidence of MAC infection as defined by at
                          least one blood culture positive for MAI or
                          AFB within 14 days prior to study entry, plus
                          a minimum of two MAC-associated symptoms
                          defined as fever OR grade 2 or worse night
                          sweats, fatigue, diarrhea, or abdominal pain
                          within 14 days prior to study entry OR a 5
                          percent or greater decrease in body weight
                          during the 60 days prior to study entry.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    CS 087250-999
STUDY DESIGN              Double-Blind; Randomized; Multicenter; 3-Arm;
                          Drug Combination
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug tolerance,
                          Combination drug therapy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 450 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Lifelong.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 44 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. HIV infection. 2. MAC infection. 3.
                          Life expectancy of at least 16 weeks. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 50000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: < 3.0 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): < 10 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): < 10 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: >= 3.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 50.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Negative pregnancy
                          test. Not pregnant. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Isoniazid for
                          TB prophylaxis ONLY.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of hypersensitivity to rifabutin,
                          rifampin, erythromycin, clarithromycin,
                          azithromycin, or ethambutol. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Positive pregnancy
                          test. Pregnant. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded within 7 days
                          prior to study entry: 1. Rifabutin. 2.
                          Rifampin. 3. Ethionamide. 4. Cycloserine. 5.
                          Clofazimine. 6. Ethambutol. 7. Amikacin. 8.
                          Ciprofloxacin. 9. Ofloxacin. 10.
                          Sparfloxacin. 11. Azithromycin. 12.
                          Clarithromycin. 13. Pyrazinamide. Excluded
                          within 14 days prior to study entry: 1.
                          Carbamazepine. 2. Terfenadine. 3.
                          Theophylline.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antimycobacterial drugs other than the study
                          drugs. 2. Carbamazepine. 3. Terfenadine. 4.
                          Theophylline.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded:
                          Perceived unreliability or unavailability for
                          frequent monitoring.
PATIENT EXCLUSION CRIT.   AVAILABILITY: Anticipated unreliability or
                          unavailability for frequent monitoring.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0099  Clarithromycin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0111  Ethambutol
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0085  Rifabutin
TRADE NAME OF SUBSTANCE   Drug 1 Biaxin
TRADE NAME OF SUBSTANCE   Drug 2 Myambutol
TRADE NAME OF SUBSTANCE   Drug 3 LM427
MANUFACTURERS             Drug 1: Abbott Laboratories One Abbott Park
                          Road Abbott Park, IL 60064 Contact: Dr J Carl
                          Craft (708) 937-8147.
MANUFACTURERS             Drug 2: Lederle Laboratories North Middletown
                          Road Pearl River, NY 10965 Contact: Dr Amy
                          Baim (914) 732-2147 Contact: Dr John Riefler
                          (914) 732-2035.
MANUFACTURERS             Drug 3: Adria Laboratories Incorporated PO
                          Box 16529 Columbus, OH 43216-6529 Contact:
                          Beverly Wynne (614) 764-8307.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 500 mg BID. Drug 2:
                          15 mg/kg daily. Drug 3: 300 or 450 mg (or
                          placebo) daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 1000 mg. Drug 2: 15
                          mg/kg. Drug 3: 300 or 450 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral.
                          Drug 3: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: Lifelong.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reasons: 1. Adverse
                          experience. 2. Considered to be treatment
                          failure.
SUPPORTING AGENCY         Adria Laboratories Incorporated.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Clarithromycin/ADVERSE EFFECTS/*THERAPEUTIC
                          USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Ethambutol/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycobacterium avium-intracellulare Infection/
                          COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Rifabutin/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       72559-06-9 (Rifabutin)
CAS REGISTRY NUMBER       74-55-5 (Ethambutol)
CAS REGISTRY NUMBER       81103-11-9 (Clarithromycin)
LAST REVISION DATE        930510
ENTRY MONTH               9307
ARIZONA                   McDowell Clinic 1314 East McDowell Road
                          Phoenix, AZ 85006 Contact: Mary Coburn (602)
                          257-0606 OPEN 931026.
ARIZONA                   Maricopa Medical Research Foundation /
                          Department of Medicin 2601 East Roosevelt
                          Phoenix, AZ 85008 Contact: Dr John Post (602)
                          267-5611 OPEN 940419.
CALIFORNIA                Combat Group 1800 North Highland Suite 610
                          Los Angeles, CA 90028 Contact: Holly Boyd
                          (213) 469-5888 OPEN 931026.
CALIFORNIA                Cedars Sinai Medical Center / Division of
                          Infectious Disease 8700 Beverley Boulevard
                          Los Angeles, CA 90048 Contact: Dr Paula Gaut
                          (310) 855-5000 OPEN 940419.
CALIFORNIA                Bay Harbor Hospital 1403 W Loma Blvd / Suite
                          201 Harbor City, CA 90710 Contact: Dr Michael
                          Nakata (310) 530-9211 OPEN 930510.
CALIFORNIA                HIV Research Group 458 26th Street San Diego,
                          CA 92102 Contact: Karen Sova (619) 544-0482
                          Contact: Dr Daniel Pearce (619) 544-0482 OPEN
                          931026.
CALIFORNIA                UCSD / Center for Special Immunology 2918
                          Fifth Ave / Suite 300 San Diego, CA 92103
                          Contact: Dr Scott Loss (619) 543-8080 OPEN
                          940419.
CALIFORNIA                Center for Special Immunology 100 Pacifica
                          Suite 100 Irvine, CA 92718 Contact: Dr Paul
                          Cimoch (714) 753-0670 OPEN 940419.
CALIFORNIA                Sunnyvale Medical Clinic 301 Old San
                          Francisco Road Sunnyvale, CA 94086 Contact:
                          Sandy Odenheimer (408) 524-5091 OPEN 931026.
CALIFORNIA                Saint Francis Memorial Hospital 900 Hyde
                          Street San Francisco, CA 94109 Contact: Dr
                          Gifford Leoung (415) 353-6216 OPEN 940419.
CALIFORNIA                General Hospital / AIDS Clinical Trials Unit
                          995 Potrero Avenue / Bldg 80 / Ward 84 San
                          Francisco, CA 94110 Contact: David Gary (415)
                          476-9296 X 846OPEN 931026 ACTU: 0808.
CALIFORNIA                Veterans Administration Medical Center 4150
                          Clement Street #111W San Francisco, CA 94121
                          Contact: Manon Marovick RN (415) 221-4810 X
                          338OPEN 931026.
DISTRICT OF COLUMBIA      George Washington University Ross Hall / Room
                          202 / 2300 I Street NW Washington, DC 20037
                          Contact: Dr David Parenti (202) 994-2417
                          Contact: Jane Courtless (202) 994-2417 OPEN
                          931026.
DISTRICT OF COLUMBIA      Veterans Administration Medical Center 50
                          Irving Street N W Washington, DC 20422
                          Contact: Dr Fred Gordon (202) 745-8695
                          Contact: Patricia Ackerson (202) 745-8695
                          OPEN 931026.
FLORIDA                   Infectious Disease Consultants / Dr Carlos
                          Ruiz 685 Palm Springs Drive / Suite 2A
                          Altamonte Springs, FL 32701 Contact: Laura
                          Hoffman (407) 830-5577 OPEN 931202.
FLORIDA                   Dr Nelson Zide 4700 / K / Sheridan Street
                          Hollywood, FL 33021 Contact: Sherry Balber
                          (305) 962-0040 Contact: Diana Bryan (305)
                          962-0040 Contact: Dr Nelson Zide (305)
                          962-0040 OPEN 931026.
FLORIDA                   Center for Special Immunology 400 Arthur
                          Godfrey Road / Suite 504 Miami Beach, FL
                          33140 Contact: Dr Robert Keller (305)
                          538-1400 OPEN 940419.
FLORIDA                   Therafirst Medical Center 4011 North Federal
                          Hwy Ft Lauderdale, FL 33308 Contact: Denise
                          LaMarca (305) 564-4222 Contact: Warren
                          Westervelt (305) 564-4222 Contact: Dr Anthony
                          LaMarca (305) 564-4222 OPEN 931026.
FLORIDA                   Dr Gary Richmond 315 Southeast 14th Street
                          Fort Lauderdale, FL 33316 Contact: Dr Gary
                          Richmond (305) 524-2250 OPEN 940419.
FLORIDA                   Dr Frank Tornaka 1625 Southeast 3rd Avenue Ft
                          Lauderdale, FL 33316 Contact: Dr. Frank
                          Tornaka OPEN 940419.
FLORIDA                   Bay Area AIDS Consortium 2901 Swann Avenue /
                          Suite 107 Tampa, FL 33609 Contact: Clinical
                          Trials Director (813) 877-5696 OPEN 931026.
FLORIDA                   Dr Bary Rodwick 960 Main Street Safety
                          Harbor, FL 34695 Contact: Dr Barry Rodwick
                          (813) 725-9931 OPEN 940419.
GEORGIA                   Infectious Disease Research Consortium of
                          Georgia 1758 Century Blvd Suite A Atlanta, GA
                          30345 Contact: Dr Winkler Weinberg (404)
                          325-4677 OPEN 931026.
ILLINOIS                  Dr Daniel Berger 2835 North Sheffield / Suite
                          104 Chicago, IL 60657 Contact: Dr Daniel
                          Berger (312) 296-2400 OPEN 940419.
KANSAS                    University of Kansas / School of Medicine
                          1010 N Kansas Wichita, KS 67214 Contact: Dr
                          Donna Sweet (316) 261-2855 OPEN 940419.
LOUISIANA                 Tulane University Medical School / AIDS
                          Clinical Trials Unit 1430 Tulane Avenue New
                          Orleans, LA 70112-2699 Contact: Russell
                          Strada (504) 584-3605 OPEN 931026.
MICHIGAN                  Dr Arnold Markowitz 2112 Cass Lake Road Keego
                          Harbor, MI 48320 Contact: Dr Arnold Markowitz
                          (810) 681-0360 OPEN 940419.
NORTH CAROLINA            Nalle Clinic 1350 South Kings Drive
                          Charlotte, NC 28287 Contact: Jan Caldwell
                          (704) 342-8100 Contact: Dr Joseph Jemsek
                          (704) 342-8318 OPEN 931026.
NEBRASKA                  University of Nebraska Medical Center / HIV
                          Clinic 600 South 42nd Street Omaha, NE
                          68198-5130 Contact: Colleen R Kelly (402)
                          559-8163 OPEN 931203.
NEW JERSEY                Veterans Administration Hospital 385 Tremont
                          Avenue East Orange, NJ 07019 Contact: Dr
                          Robert Eng (201) 676-1000 X 168OPEN 931026.
NEW JERSEY                Community Research Initiative of North Jersey
                          393 Central Avenue Newark, NJ 07102 Contact:
                          William Orr (201) 648-0350 Contact: Vicki
                          Taylor Contact: Dr George Perez OPEN 931026.
NEW YORK                  Chelsea Village Medical Center / St Vincent's
                          Hospital 314 W 14th St / 5th Flr New York, NY
                          10014 Contact: Dr David Kaufman (212)
                          620-0144 OPEN 931026.
NEW YORK                  Long Island Jewish Medical Center 269-11 76th
                          Avenue / Division of Hematological Oncology
                          New Hyde Park, NY 11042 Contact: Eileen Fusco
                          (718) 470-7698 Contact: Dr Frederick Siegal
                          (718) 470-8938 OPEN 940419.
NEW YORK                  Community Health Network 758 South Avenue
                          Rochester, NY 14620 Contact: Judy Takacs
                          (716) 244-9000 Contact: Loraine Newcomb (716)
                          244-9000 OPEN 931026.
PENNSYLVANIA              Polyclinic Medical Center 2601 North Third
                          Street Harrisburg, PA 17110 Contact: Alice
                          Boucher (717) 782-2987 OPEN 931026.
PENNSYLVANIA              Buckley Braffman Stern Medical Associates PC
                          822 Pine Street / Suite 3A Philadelphia, PA
                          19107 Contact: Nancy Pietroski (215) 925-8010
                          OPEN 931026.
SOUTH CAROLINA            Alfred F Burnside Jr M D 1640 St Julian Place
                          Suite 300 Columbia, SC 29204 Contact: John
                          Windham (803) 256-7282 OPEN 931026.
SOUTH CAROLINA            Veterans Administration Medical Center 109
                          Bee Street Charleston, SC 29401-5799 Contact:
                          Dr J. Robert Cantey (803) 577-5011 OPEN
                          940419.
 
148
UNIQUE IDENTIFIER         FDA/00641
PROTOCOL ID NUMBERS       FDA 037C
PROTOCOL TITLE            An Open-Label Safety Study of Oral
                          Ganciclovir Maintenance Treatment of CMV
                          Retinitis in People With Limited Venous
                          Access.
VERSION NUMBER & DATE     (940613)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Nationwide Access
GENERAL DESCRIPTION       PURPOSE: To provide oral ganciclovir to
                          patients who require maintenance for control
                          of cytomegalovirus (CMV) retinitis, but who
                          lack patent permanent central venous access
                          for long-term administration of intravenous
                          drugs. Methodology: Patients receive oral
                          ganciclovir as maintenance. Patients enrolled
                          at time of closure of enrollment will receive
                          2 months of study drug and undergo follow-up.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive oral
                          ganciclovir as maintenance. Patients enrolled
                          at time of closure of enrollment will receive
                          2 months of study drug and undergo follow-up.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940613)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by HIV antibody
                          test, p24 antigen assay, or HIV culture, OR
                          diagnosis of AIDS by CDC criteria. 2. Stable
                          CMV retinitis. 3. Treatment with IV
                          ganciclovir or IV foscarnet for at least 18
                          of the past 21 days. 4. Currently lack a
                          patent permanent central IV catheter. 5. Had
                          a permanent central IV catheter removed two
                          or more times within the past 6 months due to
                          catheter infection or thrombosis.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GANS2224
STUDY DESIGN              Open Label; Multicenter; Single-arm; Drug
                          Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: UNLIMITED patients.
                          (Enrollment is open until 1 month after oral
                          ganciclovir is commercially available)
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until 1 month
                          after oral ganciclovir becomes commercially
                          available.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. Stable CMV retinitis. 3.
                          Treatment with IV ganciclovir or IV foscarnet
                          for at least 18 of the past 21 days. 4. No
                          permanent central IV catheter at present. 5.
                          Had a permanent central IV catheter removed
                          two or more times within the past 6 months
                          due to catheter infection or thrombosis. 6.
                          Consent of guardian if less than legal age of
                          consent. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: > 25000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils > 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          History of hypersensitivity to acyclovir or
                          ganciclovir. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control during study and for 90 days
                          after.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Intravitreal anti-CMV treatment. 2. Any other
                          concomitant medications precluded by the
                          protocol.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: Require
                          continuation of concomitant medications
                          precluded by this protocol.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0018  Ganciclovir
MANUFACTURERS             Drug 1: Syntex Research 3401 Hillview Avenue
                          / PO Box 10850 Palo Alto, CA 94303 Contact:
                          Dr Bonnie Charpentier (415) 354-2344.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
SUPPORTING AGENCY         Syntex Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Administration, Oral
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Ganciclovir/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       82410-32-0 (Ganciclovir)
LAST REVISION DATE        940613
ENTRY MONTH               9407
CALIFORNIA                Syntex Research 3401 Hillview Avenue / PO Box
                          10850 Palo Alto, CA 94303 Contact: Study
                          Center (Physicians call) (800) 569-4630 OPEN
                          / USA accrual 940613.
 
149
UNIQUE IDENTIFIER         FDA/00640
PROTOCOL ID NUMBERS       FDA 037B
PROTOCOL TITLE            A Randomized, Controlled Study of the Safety
                          and Preventive Efficacy of Oral Ganciclovir
                          When Used in Conjunction With An Intravitreal
                          Ganciclovir Implant in the Treatment of
                          Cytomegalovirus Retinitis.
VERSION NUMBER & DATE     (940613)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To demonstrate the efficacy of oral
                          ganciclovir at a dose of 1500 mg TID in
                          preventing new cytomegalovirus (CMV) disease
                          in AIDS patients with unilateral CMV
                          retinitis treated with an intravitreal
                          ganciclovir implant. To compare safety and
                          tolerance, time to progression, quality of
                          life, and survival among patients treated
                          with an intravitreal ganciclovir implant,
                          with and without oral ganciclovir, versus
                          standard intravenous (IV) ganciclovir
                          therapy. Methodology: Patients receive
                          intravitreal ganciclovir implant plus oral
                          ganciclovir, intravitreal implant alone, or
                          IV ganciclovir.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravitreal
                          ganciclovir implant plus oral ganciclovir,
                          intravitreal implant alone, or IV
                          ganciclovir.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940607)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection by HIV antibody
                          test, p24 antigen assay, or HIV culture, OR
                          diagnosis of AIDS by CDC criteria. 2.
                          Unilateral CMV retinitis diagnosed by
                          funduscopy and confirmed by retinal
                          photographs. Previously diagnosed retinitis
                          must be of no more than 6 months duration and
                          be currently stable following at least 4
                          weeks of IV ganciclovir. No more than two
                          relapses of retinitis may have occurred since
                          original diagnosis. NOTE: Patients with past
                          or present extraocular CMV disease are not
                          eligible.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    GANS2304
STUDY DESIGN              Comparative administration route; Partially
                          Blinded; Randomized; Parallel-Group;
                          Placebo-Controlled; Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug safety, Drug efficacy,
                          Administration route comparison.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 450 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 1/450 (940607).
PROTOCOL DETAILS          STUDY DURATION: 52 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 23 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. Unilateral CMV retinitis.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 25000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 500 cells/mm3.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Topical drugs
                          and ophthalmics.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          History of previous invasive intraocular
                          surgery of any kind in the involved eye or
                          any condition for which ocular surgery in
                          contraindicated. 2. History of
                          hypersensitivity to acyclovir or ganciclovir.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control during study and for 90 days
                          after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior oral
                          ganciclovir. 2. Prior intravitreal
                          ganciclovir implant. 3. More than three prior
                          induction dose courses of IV anti-CMV
                          therapy.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Vidarabine. 2. Amantadine hydrochloride. 3.
                          Cytarabine. 4. FIAC or FIAU. 5. Idoxuridine.
                          6. Ribavirin. 7. Valacyclovir. 8. Foscarnet.
                          9. CMV hyperimmune globulin. 10. Soluble CD4.
                          11. Trichosanthin. 12. Imipenem-cilastatin.
                          13. Isoprenosine. 14. Levamisole. 15.
                          Interferon. 16. Other investigational drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Chronic, clinically significant diarrhea,
                          nausea, abdominal pain,or other symptoms of
                          uncontrolled gastrointestinal disease. 2.
                          Ocular opacities (corneal, aqueous, lens, or
                          vitreous) preventing ophthalmologic retinal
                          assessment of fundus photography. 3. Acute
                          retinal necrosis or any other intraocular
                          condition that might preclude study
                          completion. 4. Ocular condition requiring
                          immediate surgery. 5. Unable to have
                          long-term IV catheter placement.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0018  Ganciclovir
MANUFACTURERS             Drug 1: Syntex Research 3401 Hillview Avenue
                          / PO Box 10850 Palo Alto, CA 94303 Contact:
                          Dr Bonnie Charpentier (415) 354-2344.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Oral: 1500 mg TID
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Oral: 4500 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral; intravitreal
                          implant; intravenous (IV)
SUPPORTING AGENCY         Syntex Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Administration, Oral
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              Ganciclovir/*ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       82410-32-0 (Ganciclovir)
LAST REVISION DATE        940607
ENTRY MONTH               9407
CALIFORNIA                Estelle Doheny Eye Clinic 1355 San Pablo
                          Street Los Angeles, CA 90033 Contact: Laurie
                          Levin (213) 342-6466 OPEN 940613.
CALIFORNIA                Dr Neil Brourman 8641 Wilshire Blvd Suite 205
                          Beverly Hills, CA 90211 Contact: Karen Minoda
                          (310) 289-3666 Contact: Susan Bagley (310)
                          289-3666 OPEN 940613.
CALIFORNIA                Harbor UCLA Medical Center 1000 W Carson
                          Street Box 9 Torrance, CA 90509 Contact:
                          Sharon (310) 222-5189 OPEN 940613.
CALIFORNIA                University of California Irvine 19722
                          MacArthur Blvd Irvine, CA 92715 Contact: Dr
                          Baruch Kupperman (714) 856-6256 Contact:
                          (714) 856-8610 OPEN 940613.
CALIFORNIA                Dr Robert Avery 515 E Micheltorena Ave Suite
                          C Santa Barbara, CA 93103 Contact: Dr Robert
                          Avery (805) 963-1648 OPEN 940613.
CALIFORNIA                Pacific Medical Center 2340 Clay Street San
                          Francisco, CA 94115 Contact: Dr Everett Ai
                          (415) 923-3948 OPEN 940613.
CALIFORNIA                Kaiser Hospital 1600 Divisadero San
                          Francisco, CA 94115 Contact: Anna Dowling
                          (415) 202-3981 OPEN 940613.
CALIFORNIA                Santa Clara Valley Medical Center 751 S
                          Bascom Avenue San Jose, CA 95128 Contact:
                          Susan Burton (415) 364-6563 OPEN 940613.
CALIFORNIA                Dr Robert T Wendel 3939 J Street #106
                          Sacremento, CA 95819 Contact: Dana Haselwood
                          (916) 454-4861 OPEN 940613.
DISTRICT OF COLUMBIA      Dr Alan Palestine 1145 19th Street NW Suite
                          500 Washington, DC 20036 Contact: Mary
                          Henegan (202) 833-1668 OPEN 940613.
FLORIDA                   Dr Michael Stewart 1801 Barr Street Suite 715
                          Jacksonville, FL 32204 Contact: Dr Michael
                          Stewart (904) 388-8446 OPEN 940613.
FLORIDA                   Bascom Palmer 900 NW 17th Street Miami, FL
                          33136 Contact: Ruth Vandenbrouke (305)
                          326-6348 OPEN 940613.
GEORGIA                   Emory Eye Clinic 1327 Clifton Road Northeast
                          Atlanta, GA 30322 Contact: Debbie Gibbs (404)
                          248-4815 OPEN 940613.
ILLINOIS                  Dr David Weinberg 303 E Chicago Ave Ward Bldg
                          2-186 Chicago, IL 60611 Contact: Kathy
                          Naughton (312) 908-8040 OPEN 940613.
KENTUCKY                  University of Kent Medical Center Kentucky
                          Clinic Rm E303 Lexington, KY 40536 Contact:
                          Dr Harsha Sen (502) 323-5000 OPEN 940613.
MASSACHUSETTS             New England Medical Center 750 Washington
                          Street Box 450 Boston, MA 02111 Contact: Dr
                          Jay Duker (617) 956-4600 Contact:
                          Stephanie/Sec (617) 956-4604 OPEN 940613.
NEW YORK                  Dr Dorothy Friedberg 310 Lexington Ave New
                          York, NY 10016 Contact: Richard Hutt (212)
                          561-3906 OPEN 940613.
NEW YORK                  St Clares Prof Office 426 E 52nd Street New
                          York, NY 10019 Contact: Dr Kimball Woodward
                          (914) 359-7272 OPEN 940613.
NEW YORK                  New York Hospital 520 East 70th St Star
                          Pavilion New York, NY 10021 Contact: Sandi
                          Sledz (212) 746-4393 Contact: Susan
                          Wise-Cambell (212) 746-2493 OPEN 940613.
NEW YORK                  Vitreo-Retinal Consultants 944 Park Avenue
                          New York, NY 10028 Contact: Dr Ronni
                          Lieberman (212) 737-7400 OPEN 940613.
 
150
UNIQUE IDENTIFIER         FDA/00602
PROTOCOL ID NUMBERS       FDA 031F
PROTOCOL TITLE            An Open-Label Safety Program for the Use of
                          Dideoxycytidine (ddC) in Pediatric Patients
                          With Symptomatic HIV Infection Who Have
                          Failed or Are Intolerant to AZT Monotherapy,
                          or Who Have Completed Other ddC Protocols, or
                          Are Ineligible for Other Ongoing Clinical
                          Studies.
VERSION NUMBER & DATE     (940307)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Child
TRIAL CATEGORY            Nationwide Access
GENERAL DESCRIPTION       PURPOSE: To allow, on a compassionate use
                          basis, dideoxycytidine (ddC) for pediatric
                          patients with symptomatic HIV disease who
                          have failed treatment or who are intolerant
                          to zidovudine (AZT), or who have completed
                          other ddC protocols, or who are ineligible
                          for ongoing clinical trials. Methodology:
                          Patients receive ddC and are evaluated at
                          study entry and every 3 months thereafter,
                          until 3 months after ddC becomes approved for
                          pediatric patients or the sponsor deems it
                          necessary to terminate the protocol.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive ddC and are
                          evaluated at study entry and every 3 months
                          thereafter, until 3 months after ddC becomes
                          approved for pediatric patients or the
                          sponsor deems it necessary to terminate the
                          protocol.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940101)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Symptomatic HIV infection. 2.
                          Failed or intolerant to AZT monotherapy OR
                          completed other ddC protocols OR ineligible
                          for other ongoing clinical trials. NOTE:
                          Patients who do not meet the eligibility
                          requirements may discuss their cases with the
                          medical monitor.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    NV14610
STUDY DESIGN              Open Label; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Compassionate use, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 600 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: Until 3 months
                          after ddC becomes approved for pediatric
                          patients or study is terminated.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Symptomatic HIV infection. 2.
                          Failure on or intolerance to AZT monotherapy
                          OR completed other ddC protocols OR been
                          ineligible for other ongoing clinical trials.
                          NOTE: Patients who do not meet the
                          eligibility requirements may discuss their
                          cases with the medical monitor. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 03 Months - 11 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 12 Years - 99
                          Years.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0015  Dideoxycytidine
TRADE NAME OF SUBSTANCE   Drug 1 HIVID
MANUFACTURERS             Drug 1: Hoffmann-La Roche, Incorporated 340
                          Kingsland Street Nutley, NJ 07110-1199
                          Contact: Professional Services (800)
                          526-6367.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 0.01 or 0.005 mg/kg
                          q 8 hr (at investigator's discretion)
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 0.03 or 0.015 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral, 0.1 mg/ml syrup
OTHER TREATMENT INFO.     TREATMENT DURATION: Until 3 months after ddC
                          becomes approved for pediatric patients or
                          study is terminated.
OTHER TREATMENT INFO.     END POINT: Serious adverse experiences.
SUPPORTING AGENCY         Hoffmann-La Roche, Incorporated.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Acquired Immunodeficiency Syndrome/*DRUG
                          THERAPY
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Zalcitabine/*ADVERSE EFFECTS
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        940101
ENTRY MONTH               9403
NEW JERSEY                Hoffmann-La Roche Incorporated 340 Kingsland
                          Street Nutley, NJ 07110 Contact: ddC Coord
                          Center (12-5 pm EST) (800) 332-2144 OPEN /
                          USA accrual 940101.
 
151
UNIQUE IDENTIFIER         FDA/00131
PROTOCOL ID NUMBERS       FDA 029G
PROTOCOL TITLE            An Open Label Evaluation of the Safety and
                          Pharmacokinetics of Ganciclovir in Children.
VERSION NUMBER & DATE     (900427)
TRIAL CATEGORY            Child
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To evaluate the pharmacokinetics of
                          intravenous ganciclovir in children (ages 3
                          months - 12 years). To determine the safety
                          and tolerance of a 2 to 3 week induction
                          course of ganciclovir IV (5mg/kg every 12
                          hours) in immunocompromised children
                          receiving treatment for life- or
                          sight-threatening cytomegalovirus infections.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940613)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: Congenital or acquired immune
                          deficiency including: AIDS. Iatrogenic
                          immunosuppression for transplantation or for
                          autoimmune disorders. Immunosuppression due
                          to cytotoxic chemotherapy. immunodeficiency
                          associated with neoplasia. Congenital
                          immunodeficiency. Eligible to receive
                          ganciclovir for the treatment of life- or
                          sight-threatening Cytomegalovirus (CMV)
                          disease as defined below. o CMV retinitis
                          confirmed by an ophthalmologist. o
                          Life-threatening CMV disease such as
                          pneumonia, gastrointestinal disease,
                          hepatitis, or other organ specific or
                          disseminated disease, or CMV viremia,
                          detection of CMV antigenemia, or CMV viruria
                          which, in the opinion of the investigator, is
                          an indication of life-threatening CMV
                          disease. CMV disease should be confirmed by
                          appropriate diagnostic procedures: (1)
                          Inclusion bodies consistent with CMV, or (2)
                          A positive CMV culture of the specific
                          tissue, or (3) A positive CMV DNA
                          hybridization probe assay of the specific
                          tissue, or (4) An immunochemically specific
                          identification of the CMV antigen. Children
                          are allowed if: 1. Appropriate diagnostic
                          procedures necessary to obtain organ specific
                          virologic confirmation have been undertaken
                          and all available histologic, or immunologic
                          tests and cultures have been requested. 2.
                          The investigator indicates that the disease
                          is immediately life-threatening and delay in
                          treatment while awaiting test results would
                          put the patient at increased risk. 3. There
                          is laboratory evidence of acute CMV infection
                          such as seroconversion, four-fold increase in
                          CMV titer, or viral isolation or positive
                          rapid diagnostic test from another site
                          (viremia, viruria, throat washings, etc.). If
                          cultures, DNA probe, and immunologic testing
                          remain negative and if the patient fails to
                          respond to ganciclovir the drug should be
                          discontinued. If cultures and probe remain
                          negative but the patient appears to respond
                          to theray, clinical judgement may support
                          continuing of ganciclovir treatment.
                          Underlying immunodeficiency is required;
                          infants and children with congenital CMV
                          infection but no immunodeficiency disorder
                          will not be eligible for this study.
ELIGIBILITY               AIDS. OTHER - immunocompromised.
OTHER PROTOCOL NUMBERS    ICM 1788
STUDY DESIGN              Open Label
PROTOCOL DETAILS          STUDY INTENT: Pharmacokinetics, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 20 patients.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 16/20 (940309).
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 8 units.
INPATIENT/OUTPATIENT ST.  Inpatient or outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have the following: Congenital or acquired
                          immune deficiency. Eligiblity to receive
                          ganciclovir for the treatment of life- or
                          sight-threatening Cytomegalovirus (CMV)
                          disease. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 25000 platelets/mm3. (with
                          some exceptions).
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophil count (ANC) >= 500
                          cells/mm3. (with some exceptions).
PATIENT AGE               AGE: 03 Months - 12 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Negative pregnancy test.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: Topical
                          acyclovir. Consult with the Syntex study
                          monitor for the following: Cytokines. Soluble
                          CD4. Trichosanthin (Compound Q).
                          Imipenem-cilastatin. Other investigational
                          drugs.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following are excluded: o Mild to moderate
                          Cytomegalovirus (CMV) infection that does not
                          meet the clinical severity criteria. o
                          Absolute neutrophil count (ANC) < 500
                          cells/mm3 or a platelet count < 25000
                          platelets/mm3. Note: Exceptions may be made
                          for patients with pre-existing neutropenia or
                          thrombocytopenia and immediately
                          life-threatening disease, if the investigator
                          believes that a delay in starting ganciclovir
                          therapy is not advisable. In such patients,
                          the investigator should advise the parents or
                          guardians of the risk of further bone marrow
                          suppression and the increased risk of
                          infection or bleeding. o Receiving excluded
                          medications that it is not possible to
                          discontinue. o Congenital or neonatal CMV
                          infections without documented congenital or
                          acquired immunodeficiency. o Demonstrated
                          hypersensitivity to acyclovir or ganciclovir.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 02 Months. 13 Years - 99
                          Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. Positive pregnancy test. No
                          abstinence or no agreement to use effective
                          method of birth control / contraception
                          during the study.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Other
                          myelosuppressive drugs. Antimetabolites.
                          Alkylating agents. Nucleoside analogues
                          (topical acyclovir is allowed). Interferons.
                          Foscarnet. Consult with the Syntex study
                          monitor for the following: Cytokines. Soluble
                          CD4. Trichosanthin (Compound Q).
                          Imipenem-cilastatin. Other investigational
                          drugs.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions or symptoms are excluded: Mild to
                          moderate Cytomegalovirus infection that does
                          not satisfy the clinical severity criteria.
                          Congenital or neonatal CMV infections without
                          documented congenital or acquired
                          immunodeficiency.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0018  Ganciclovir
TRADE NAME OF SUBSTANCE   Drug 1 Cytovene
MANUFACTURERS             Drug 1: Syntex Research 3401 Hillview Avenue
                          / PO Box 10850 Palo Alto, CA 94303 Contact:
                          Dr Bonnie Charpentier (415) 354-2344.
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: IV
SUPPORTING AGENCY         Syntex Research.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Child
MESH HEADING              Child, Preschool
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Ganciclovir/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Immunocompromised Host
MESH HEADING              Infant
MESH HEADING              Male
MESH HEADING              Retinitis/COMPLICATIONS/DRUG THERAPY
CAS REGISTRY NUMBER       82410-32-0 (Ganciclovir)
LAST REVISION DATE        940613
ENTRY MONTH               9008
ALABAMA                   University of Alabama at Birmingham 653
                          Childrens Hospital Tower UAB Station
                          Birmingham, AL 35294 Contact: Dr Richard
                          Whitley (205) 934-5316 OPEN.
CALIFORNIA                The Center for the Health Sciences / UCLA
                          10833 Le Conte Avenue Room 22-442 MDCC Los
                          Angeles, CA 90024 Contact: Dr Yvonne Bryson
                          (310) 825-5235 OPEN.
CALIFORNIA                Children's Hospital of Los Angeles 4650
                          Sunset Boulevard Los Angeles, CA 90027
                          Contact: Dr Carl Lenarsky (213) 669-2546
                          OPEN.
CALIFORNIA                Los Angeles County Hospital / USC Medical Ctr
                          / Pediatrics 1200 North State Street Los
                          Angeles, CA 90033 Contact: Dr Andrea Kovacs
                          (213) 226-3834 OPEN.
ILLINOIS                  University of Chicago / Wylers 5841 South
                          Maryland Avenue / Box 286 / Room C-623A
                          Chicago, IL 60637 Contact: Dr Daniel Johnson
                          (312) 702-6176 OPEN.
NEBRASKA                  University of Nebraska Medical Center 600
                          South 42nd Street Omaha, NE 68198-3280
                          Contact: Dr Mark Schaefer (402) 559-4000
                          Contact: Beeper OPEN.
NEW YORK                  University of Rochester Medical Center 601
                          Elmwood Avenue / Box 690 Rochester, NY 14642
                          Contact: Dr Lisa M Frenkel (716) 275-5944
                          OPEN 920409.
 
152
UNIQUE IDENTIFIER         FDA/00679
PROTOCOL ID NUMBERS       FDA 025C
PROTOCOL TITLE            Phase IV Study on the Safety and Efficacy of
                          Megace Oral Suspension in HIV-Positive
                          Females.
VERSION NUMBER & DATE     (941003)
GENERAL DESCRIPTION       PURPOSE: To further evaluate the safety of
                          megestrol acetate (Megace) oral suspension in
                          the treatment of anorexia and cachexia in
                          HIV-positive women. To compare the
                          effectiveness of 400 versus 800 mg daily of
                          Megace by measurement of weight gain,
                          appetite grade, and other parameters at 12
                          and 24 weeks. Methodology: Patients are
                          randomized to receive 400 or 800 mg Megace
                          oral suspension daily for 24 weeks; at 12
                          weeks, those receiving 400 mg who have not
                          gained 5 pounds over baseline or had appetite
                          improvement to good or excellent are
                          escalated to 800 mg daily. Patients are
                          evaluated at 4 week intervals. Dose may be
                          adjusted to maintain a desired weight.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive 400 or 800 mg Megace oral suspension
                          daily for 24 weeks; at 12 weeks, those
                          receiving 400 mg who have not gained 5 pounds
                          over baseline or had appetite improvement to
                          good or excellent are escalated to 800 mg
                          daily. Patients are evaluated at 4 week
                          intervals. Dose may be adjusted to maintain a
                          desired weight.
PROTOCOL PHASE            Phase IV
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940817)
DISEASE STUDIED           Anorexia, Cachexia.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV seropositive. 2. Evidence
                          of HIV wasting syndrome that includes
                          anorexia (appetite fair or poor) and weight
                          loss >= 10 percent of pre-illness body
                          weight.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    MEG169-93.007
STUDY DESIGN              Dose Comparison; Randomized; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 40 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 24 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 4 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patient must
                          have: 1. HIV infection. 2. Evidence of HIV
                          wasting syndrome that includes anorexia
                          (appetite fair or poor) and weight loss >= 10
                          percent of pre-illness body weight. 3.
                          Perception of weight loss as a detriment. 4.
                          Life expectancy of at least 24 weeks. [Refer
                          to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Allowed: Megestrol acetate
                          for weight gain at a dose < 400 mg for < 60
                          days, provided therapy was discontinued at
                          least 3 months prior to study entry.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Hospitalization for or exacerbation of
                          illness associated with weight loss within
                          the past 2 weeks. 2. Participation in other
                          investigational drug studies within the past
                          month. 3. Previous abnormal mammogram (if
                          35-40 years of age) or abnormal mammogram
                          within the past year (if over 40 years of
                          age). [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   SEX: MALE; FEMALE
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: IV drug abuse not treated for
                          at least 4 months.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. New antiviral
                          therapy within the past 8 weeks. 2.
                          Medications to promote weight gain (e.g.,
                          corticosteroid, dronabinol) within the past 2
                          months. 3. Megestrol acetate within the past
                          3 months.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Initiation
                          during the study of any therapy to treat HIV
                          or anorexia/cachexia (other than study drug).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Poorly controlled hypertension. 2. Heart
                          failure. 3. Deep vein thrombosis. 4.
                          Uncontrolled severe diarrhea. 5. Treatable
                          active current infection (excluding chronic
                          low-grade opportunistic infections). 6.
                          Unable to intake food. 7. Impaired
                          digestive/absorptive function.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0063  Megestrol acetate
TRADE NAME OF SUBSTANCE   Drug 1 Megace
MANUFACTURERS             Drug 1: Bristol-Myers Squibb 777 Scudders
                          Mill Road Plainsboro, NJ 08536 Contact: Judy
                          Wagner (609) 897-2132.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 400 or 800 mg daily
                          for 24 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 400 or 800 mg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
OTHER TREATMENT INFO.     TREATMENT DURATION: 24 weeks.
SUPPORTING AGENCY         Bristol-Myers Squibb.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Anorexia/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Cachexia/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Human
MESH HEADING              Megestrol/ADMINISTRATION & DOSAGE/ADVERSE
                          EFFECTS/*THERAPEUTIC USE
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       3562-63-8 (Megestrol)
LAST REVISION DATE        940817
ENTRY MONTH               9410
CALIFORNIA                University of California / Davis Medical
                          Center 2221 Stockton Blvd Sacramento, CA
                          95817 Contact: Dr Neil Flynn (916) 734-3793
                          OPEN 940817.
CONNECTICUT               Yale Medical School / AIDS Program 135
                          College Street / Suite 323 New Haven, CT
                          06510-2483 Contact: Dr Gerald Friedland (203)
                          737-2450 OPEN 940817.
DISTRICT OF COLUMBIA      Georgetown University Medical Center 3800
                          Reservoir Road / Kober-Cogan Bldg Suite 110
                          Washington, DC 20007-2197 Contact: Dr Mary
                          Young (202) 687-3200 OPEN 940817.
RHODE ISLAND              The Miriam Hospital 164 Summit Avenue
                          Providence, RI 02906 Contact: Dr Maria Mileno
                          (401) 331-8500 X 402OPEN 940817.
 
153
UNIQUE IDENTIFIER         FDA/00687
PROTOCOL ID NUMBERS       FDA 020I
PROTOCOL TITLE            Phase III Multicenter, Open-Label, Randomized
                          Trial of Induction Versus Induction Plus
                          Maintenance Foscarnet ( Foscavir ) Therapy
                          for Gastrointestinal CMV Disease.
VERSION NUMBER & DATE     (941206)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: PRIMARY: To compare the frequency of
                          and time to relapse of Cytomegalovirus (CMV)
                          gastrointestinal disease following foscarnet
                          induction therapy only versus induction plus
                          maintenance therapy. SECONDARY: To determine
                          frequency of and time to recurrence of
                          gastrointestinal symptoms, response rate of
                          pathological lesions, and incidence of
                          nongastrointestinal CMV disease in this
                          patient population. Methodology: Patients
                          receive intravenous foscarnet either as
                          induction only for 4 weeks or as induction
                          for 4 weeks followed by maintenance for 22
                          weeks. All patients are followed for 26 weeks
                          or until relapse.
GENERAL DESCRIPTION       METHODOLOGY: Patients receive intravenous
                          foscarnet either as induction only for 4
                          weeks or as induction for 4 weeks followed by
                          maintenance for 22 weeks. All patients are
                          followed for 26 weeks or until relapse.
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (941206)
DISEASE STUDIED           Cytomegalovirus ( CMV ) gastrointestinal
                          disease.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. AIDS. 2. Symptomatic CMV
                          disease of the upper and/or lower
                          gastrointestinal (GI) tract. 3. CMV GI
                          disease is a first episode OR patient either
                          failed a prior single course of up to 4 weeks
                          of intravenous ganciclovir induction therapy
                          or is intolerant of ganciclovir.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    93-FOS-29
STUDY DESIGN              Multicenter; Open Label; Randomized
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 145 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 26 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 16 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. AIDS. 2. CMV GI disease. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 14 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 14 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control during
                          study and for 90 days after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Prior
                          foscarnet in extremis. 2. Investigational
                          agents other than 3TC or d4T within 7 days
                          prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Drugs
                          that may interact with foscarnet. 2. Systemic
                          acyclovir, ganciclovir, or acyclovir prodrug.
                          3. Drugs known to affect renal function.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Non-GI CMV disease. 2. Ulcerative colitis,
                          inflammatory bowel disease, or other
                          condition that may interfere with study
                          results. 3. Other GI pathogens.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0017  Foscarnet sodium
TRADE NAME OF SUBSTANCE   Drug 1 Foscavir
MANUFACTURERS             Drug 1: Astra USA Inc 50 Otis Street
                          Westborough, MA 01581 Contact: Dr Sarah
                          Martin-Munley (508) 366-1100 X 2309.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: Induction: 90 mg/kg
                          BID for 4 weeks. Maintenance: 120 mg/kg/day
                          for 22 weeks
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: Induction: 180 mg/kg.
                          Maintenance: 120 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV)
OTHER TREATMENT INFO.     TREATMENT DURATION: Up to 26 weeks.
SUPPORTING AGENCY         Astra USA Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Foscarnet/*ADMINISTRATION & DOSAGE/
                          THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
CAS REGISTRY NUMBER       4428-95-9 (Foscarnet)
LAST REVISION DATE        941206
ENTRY MONTH               9412
CALIFORNIA                Los Angeles - USC Medical Center / GI and
                          Liver Disease 1200 North State Street / Room
                          12-137 Los Angeles, CA 90033 Contact:
                          Francisco Garcia (213) 226-6939 Contact: Dr
                          Loren Laine (213) 226-7994 Contact: (213)
                          226-7995 OPEN 941206.
CALIFORNIA                University of California San Diego 2760 Fifth
                          Avenue / Suite 300 San Diego, CA 92103
                          Contact: UCSD Treatment Center (619) 543-8080
                          OPEN 941206.
CALIFORNIA                San Francisco General Hospital 1001 Potrero
                          Avenue San Francisco, CA 94110 Contact: Ulana
                          Mencinski (415) 206-4746 Contact: Dr Paul
                          Greenberg (415) 206-8824 Contact: Dr John P
                          Cello (415) 206-8822 OPEN 941206.
CALIFORNIA                East Bay AIDS Center 3031 Telegraph Avenue /
                          Suite 235 Berkeley, CA 94705 Contact: Sherry
                          Lyman (510) 204-1870 Contact: Dr Carol
                          Brosgart (510) 204-1201 OPEN 941206.
FLORIDA                   Miami Veterans Administration Medical Center
                          1201 NW 16th Street / Special Immunology Unit
                          / Dept 111-I Miami, FL 33125 Contact:
                          Ghislaine Paperwalla RN (305) 324-4455 X
                          352Contact: Karen Clevens NP Contact: Dr
                          Nancy Klimas (305) 324-4455 X 433OPEN 941206.
GEORGIA                   Emory University School of Medicine / GI
                          Division 69 Butler Street SE Atlanta, GA
                          30303 Contact: Lorraine Alexander (404)
                          616-4436 Contact: Dr C Mel Wilcox (404)
                          616-4435 Contact: Fax (404) 522-0404 OPEN
                          941206.
ILLINOIS                  Rush Presbyterian - St Lukes Medical Center
                          600 South Paulina / Suite 143 / Academic
                          Facility Chicago, IL 60612 Contact: Michelle
                          Agnoli (312) 942-5865 Contact: Dr Harold
                          Kessler OPEN 941206.
ILLINOIS                  Rush Presbyterian - St Lukes Medical Center
                          1725 West Harrison Street / Professional
                          Building Chicago, IL 60612 Contact: Janice
                          Griffin (312) 942-5861 Contact: Dr Michael
                          Brown (312) 942-5861 Contact: Mary Elizabeth
                          Roarke Contact: Ruth Ann Burk OPEN 941206.
MICHIGAN                  Dr Robert Bresalier / Henry Ford Hospital
                          Main Campus / 2799 West Grand Blvd Detroit,
                          MI 48202 Contact: Sandra Wilson (313)
                          876-9452 OPEN 941206.
NEW YORK                  Dr Douglas Dieterich 345 East 37th Street
                          Suite 204 New York, NY 10016 Contact:
                          Kathleen Farrell (212) 263-6485 Contact: Dr
                          Douglas Dieterich (212) 986-3330 OPEN 941206.
NEW YORK                  Dept of Vet Affairs Med Ctr (632) /
                          Gastroenterology Section 79 Middleville Road
                          Northport, NY 11768 Contact: Mary Garcia
                          (516) 261-4400 X 247OPEN 941206.
OHIO                      Ohio State University Hospital Doan Hall /
                          Room N 1148 / 410 West Tenth Avenue Columbus,
                          OH 43210 Contact: Dr Maybeth Ramundo (614)
                          293-8112 OPEN 941206.
 
154
UNIQUE IDENTIFIER         FDA/00617
PROTOCOL ID NUMBERS       FDA 020H
PROTOCOL TITLE            A Multicenter Study of Oral Versus
                          Intravenous Hydration in AIDS Patients With
                          CMV Retinitis Treated With Foscavir.
VERSION NUMBER & DATE     (940329)
TRIAL CATEGORY            Opportunistic Infections
PROTOCOL CHAIRS           CHAIR  Wool GM
GENERAL DESCRIPTION       PURPOSE: To assess the relative efficacy of
                          oral versus intravenous hydration during
                          foscarnet sodium (Foscavir) induction therapy
                          (90 mg/kg BID), as determined by changes in
                          creatinine clearance. To estimate the timing
                          and volume of oral fluid hydration required
                          to establish a diuresis before and during
                          intravenous Foscavir therapy. To assess the
                          general tolerance of two hydration regimens
                          by the adverse event profile associated with
                          each. Methodology: Patients are randomized to
                          receive oral hydration versus intravenous
                          hydration therapy during concomitant
                          intermittent intravenous Foscavir therapy for
                          treatment of cytomegalovirus (CMV) retinitis.
                          Treatment continues during 2 or 3 weeks of
                          induction Foscavir therapy.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive oral hydration versus intravenous
                          hydration therapy during concomitant
                          intermittent intravenous Foscavir therapy for
                          treatment of cytomegalovirus (CMV) retinitis.
                          Treatment continues during 2 or 3 weeks of
                          induction Foscavir therapy.
PROTOCOL PHASE            Phase IV
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940301)
DISEASE STUDIED           Cytomegalovirus retinitis ( CMV retinitis ).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Documented HIV infection. 2.
                          Recent diagnosis of CMV retinitis, by
                          ophthalmoscopic appearance, that requires
                          induction therapy. 3. No corneal, lens, or
                          vitreous opacification that precludes
                          examination of the fundi. 4. No evidence of
                          other end organ CMV infection. 5. No evidence
                          of tuberculous, diabetic, or hypertensive
                          retinopathy.
ELIGIBILITY               AIDS.
OTHER PROTOCOL NUMBERS    93-FOS-31
STUDY DESIGN              Open Label; Randomized; Comparative
                          administration route; Prospective;
                          Multicenter
PROTOCOL DETAILS          STUDY INTENT: Administration route
                          comparison.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 112 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 2-3 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 11 units.
INPATIENT/OUTPATIENT ST.  Outpatient
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. Recent
                          diagnosis of CMV retinitis, by
                          ophthalmoscopic appearance, that requires
                          induction therapy. 3. No corneal, lens, or
                          vitreous opacification that precludes
                          examination of the fundi. 4. No evidence of
                          other end organ CMV infection. 5. No evidence
                          of tuberculous, diabetic, or hypertensive
                          retinopathy. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: >= 50 ml/min.
PATIENT INCLUSION CRIT.   KARNOFSKY: >= 60.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 7 days of study entry.
                          Abstinence or effective method of birth
                          control / contraception during the study and
                          for 90 days after.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 7 days of study entry.
                          No abstinence or no agreement to use
                          effective method of birth control during
                          study and for 90 days after.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: 1. Any
                          investigational drug within 28 days prior to
                          study entry. 2. Potentially nephrotoxic drugs
                          (e.g., amphotericin B, aminoglycosides,
                          cisplatin) within 7 days prior to study
                          entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          investigational drug. 2. Potentially
                          nephrotoxic drugs (e.g., amphotericin B,
                          aminoglycosides, cisplatin).
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Clinically significant cardiac, pulmonary,
                          neurologic, gastrointestinal or renal
                          impairment that would prevent adequate
                          voluntary oral hydration (e.g., intubation,
                          coma, status post-gastrectomy, colon
                          resection, gastrointestinal tumors,
                          malabsorption, chronic diarrhea) OR with
                          which hydration would be hazardous (e.g.,
                          congestive heart failure). 2. Known allergy
                          to foscarnet or related compounds. 3.
                          Considered noncompliant or unreliable for
                          study participation.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0017  Foscarnet sodium
TRADE NAME OF SUBSTANCE   Drug 1 Foscavir
MANUFACTURERS             Drug 1: Astra USA Inc 50 Otis Street
                          Westborough, MA 01581 Contact: Dr Sarah
                          Martin-Munley (508) 366-1100 X 2309.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 90 mg/kg BID
                          accompanied by either oral or intravenous
                          hydration
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 180 mg/kg
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Intravenous (IV)
OTHER TREATMENT INFO.     TREATMENT DURATION: 2-3 weeks.
SUPPORTING AGENCY         Astra USA Inc.
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Administration, Oral
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Cytomegalovirus Infections/COMPLICATIONS/
                          *DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Fluid Therapy
MESH HEADING              Foscarnet/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Infusions, Intravenous
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Retinitis/COMPLICATIONS/*DRUG THERAPY
CAS REGISTRY NUMBER       4428-95-9 (Foscarnet)
LAST REVISION DATE        940301
ENTRY MONTH               9404
CALIFORNIA                Dr Milan Fiala 100 UCLA Medical Plaza / Suite
                          100 Los Angeles, CA 90024-6970 Contact: Dr
                          Milan Fiala (310) 206-6392 OPEN 940301.
CALIFORNIA                Dr G Michael Wool Century City Plaza / 2080
                          Century Park East / Suite 1006 Los Angeles,
                          CA 90067 Contact: Andrew Miranda (310)
                          556-7991 OPEN 940301.
CALIFORNIA                Dr Ralph Hansen 436 North Bedford Drive /
                          Suite 308 Beverly Hills, CA 90210 Contact:
                          Marilyn Irwin (310) 246-6550 OPEN 940301.
CALIFORNIA                AIDS Community Research Consortium 1048 El
                          Camino Real Redwood City, CA 94063 Contact:
                          Debbie Harris (415) 364-6563 Contact: Dr
                          Stanley Deresinski OPEN 940301.
GEORGIA                   Dr Joel Rosenstock 35 Collier Road / Suite
                          245 Atlanta, GA 30309 Contact: Kym Prieto
                          (404) 325-4677 OPEN 940301.
INDIANA                   Dr John Karedes Bank One Tower / 111 Monument
                          Circle / Suite 3010 Indianapolis, IN 46204
                          Contact: Reba Baker (317) 638-2005 OPEN
                          940301.
MICHIGAN                  Dr Paul Benson 2327 Coolidge Berkley, MI
                          48072 Contact: David Rock (810) 544-9300 OPEN
                          940301.
NEW JERSEY                Dr Ronald Nahass 411 Courtyard Drive
                          Somerville, NJ 08876 Contact: Debbie Winters
                          (609) 497-1068 OPEN 940301.
NEW YORK                  Dr Ronald J Grossman 345 East 37th Street /
                          Suite 209 New York, NY 10016 Contact: Jeff
                          Silverstein (212) 818-0853 OPEN 940301.
NEW YORK                  Community Health Network 758 South Avenue
                          Rochester, NY 14620 Contact: Judy Takacs
                          (716) 244-9000 Contact: Loraine Newcomb (716)
                          244-9000 OPEN 940301.
 
155
UNIQUE IDENTIFIER         FDA/00616
PROTOCOL ID NUMBERS       FDA 015I
PROTOCOL TITLE            Double-Blind Study of the Effect of Timunox
                          (Thymopentin) on Lymphoproliferative
                          Responses and Virus Load in HIV-Infected
                          Subjects Receiving Nucleoside Analog
                          Antiretroviral Therapy.
VERSION NUMBER & DATE     (940420)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To evaluate the mechanism whereby
                          thymopentin appears to retard the progressive
                          immune suppression attributable to HIV
                          infection. Methodology: Patients are
                          randomized to receive subcutaneous
                          thymopentin or placebo thrice weekly for 4
                          weeks.
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive subcutaneous thymopentin or placebo
                          thrice weekly for 4 weeks.
PROTOCOL PHASE            Phase II
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940401)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Seropositive for HIV-1
                          antibody by ELISA confirmed by Western blot.
                          2. CD4 count <= 400 cells/mm3 within 6 weeks
                          prior to study entry. 3. Must have tolerated
                          their current nucleoside analog
                          antiretroviral treatment (zidovudine,
                          didanosine, or dideoxycytidine) for at least
                          4 weeks prior to study entry. 4. Asymptomatic
                          or minimally symptomatic disease, as defined
                          by ABSENCE of the following: - HIV-associated
                          neurologic abnormalities - Oral hairy
                          leukoplakia - Unintentional weight loss
                          greater than 10 percent of usual body weight
                          - Unexplained temperature above 38 C on five
                          or more consecutive days or 10 days within
                          any 30-day period - Five or more episodes of
                          unexplained drenching night sweats in any
                          30-day period - Unexplained diarrhea for 7 or
                          more consecutive days in any 30-day period -
                          Vulvovaginal candidiasis that is persistent
                          (poorly responsive to local therapy) or
                          frequent (> three episodes/year). NOTE:
                          Patients may have had NO MORE THAN ONE of the
                          following conditions prior to entry: - Herpes
                          zoster infection within the last 2 years -
                          Confirmed oral candidiasis - Bacillary
                          angiomatosis - Listeriosis.
ELIGIBILITY               ASYM. ARC.
OTHER PROTOCOL NUMBERS    07.32.039-94
STUDY DESIGN              Double-Blind; Randomized; Placebo-Controlled;
                          Multicenter
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy.
PROTOCOL DETAILS          PROJECTED ACCRUAL: 60 patients.
PROTOCOL DETAILS          DURATION OF PATIENT ON STUDY: 4 weeks.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic or minimally
                          symptomatic HIV infection (no evidence of
                          AIDS). 2. CD4 count <= 400 cells/mm3 within 6
                          weeks prior to study entry. 3. Tolerated the
                          current nucleoside analog antiretroviral
                          treatment for at least 4 weeks prior to study
                          entry. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 11 g/dl. (men); >= 10 g /dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: <= 400 cells/mm3. ( 0 -
                          100 - 200 - 300 - 400 ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: 90.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 21 days prior to study
                          entry. Not breast-feeding. Abstinence or
                          effective method of birth control /
                          contraception including oral contraceptives
                          during the study.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Nucleoside analog
                          antiretroviral treatment for at least 4 weeks
                          prior to study entry.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Required: Current
                          nucleoside analog antiretroviral treatment.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior condition are excluded:
                          Abnormal chest x-ray consistent with active
                          opportunistic infection within 6 weeks prior
                          to study entry. [Refer to Laboratory values
                          for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 21 days prior to study
                          entry. Breast-feeding. No abstinence or no
                          agreement to use effective method of birth
                          control / contraception during the study.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Significant active alcohol or
                          drug abuse sufficient to prevent study
                          compliance.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Any prior
                          antiretroviral agents other than zidovudine,
                          didanosine, or dideoxycytidine within 30 days
                          prior to study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. Any
                          antiretroviral agents other than zidovudine,
                          didanosine, or dideoxycytidine. 2. HIV
                          vaccines or any investigational or non-FDA
                          approved medication or immunomodulatory or
                          experimental therapy within 30 days prior to
                          study entry.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1. Known
                          hypersensitivity to thymopentin or any
                          component of the formulation. 2. Significant
                          chronic underlying medical illness that would
                          impede study participation. 3. Grade 2 or
                          higher peripheral neuropathy related to
                          nucleoside analog antiretroviral treatment.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0065  Thymopentin
TRADE NAME OF SUBSTANCE   Drug 1 Timunox
MANUFACTURERS             Drug 1: Immunobiology Research Institute
                          Route 22 East PO Box 999 Annandale, NJ
                          08801-0999 Contact: Linda Meyerson (908)
                          730-1750.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 50 mg (or placebo)
                          thrice weekly for 4 weeks
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous
OTHER TREATMENT INFO.     END POINT: Lymphoproliferative responses,
                          T-cell subsets, apoptosis, and HIV viral RNA
                          levels.
SUPPORTING AGENCY         Immunobiology Research Institute.
MESH HEADING              AIDS-Related Complex/*DRUG THERAPY
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Thymopentin/*THERAPEUTIC USE
CAS REGISTRY NUMBER       69558-55-0 (Thymopentin)
LAST REVISION DATE        940401
ENTRY MONTH               9404
CALIFORNIA                Dr Jeffrey Galpin 5620 Wilbur Avenue / Suite
                          322 Tarzana, CA 91356 Contact: Vicki Ramirez
                          (818) 345-2172 OPEN 940401.
CALIFORNIA                Dr Marcus Conant 1635 Divisadero Street San
                          Francisco, CA 94115 Contact: Tanya Kocian
                          (415) 923-0222 OPEN 940401.
PENNSYLVANIA              Novum Inc 5900 Penn Avenue Pittsburgh, PA
                          15206 Contact: Sharon Grace (412) 363-3300
                          OPEN 940401.
 
156
UNIQUE IDENTIFIER         FDA/00576
PROTOCOL ID NUMBERS       FDA 015H
PROTOCOL TITLE            Double-Blind Study of Timunox (Thymopentin)
                          in Asymptomatic HIV-Infected Patients
                          Receiving Either Mono (AZT or ddI) or
                          Combination (AZT/ddI or AZT/ddC)
                          Anti-Retroviral Therapy.
VERSION NUMBER & DATE     (940725)
TRIAL CATEGORY            HIV Infection
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To confirm results from a previous
                          study in which the combination of thymopentin
                          plus zidovudine (AZT), an antiretroviral
                          agent, slowed disease progression in
                          HIV-infected asymptomatic patients. To
                          evaluate the efficacy and safety of
                          thymopentin in HIV-infected asymptomatic
                          patients receiving either monotherapy with
                          AZT, didanosine (ddI), or stavudine (d4T), or
                          combination antiretroviral therapy with
                          AZT/ddI or AZT/dideoxycytidine (ddC).
PROTOCOL PHASE            Phase III
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940511)
DISEASE STUDIED           Primary HIV infection.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. Asymptomatic HIV infection. 2.
                          CD4 count 200-400 cells/mm3. 3. No
                          HIV-associated neurologic abnormalities or
                          constitutional symptoms. 4. No oral hairy
                          leukoplakia. 5. At least 6 months of prior
                          AZT or at least 4 weeks of prior d4T or ddI
                          OR prior combination therapy with AZT/ddI or
                          AZT/ddC.
ELIGIBILITY               ASYM.
OTHER PROTOCOL NUMBERS    07.32.033-93
STUDY DESIGN              Double-Blind; Randomized; Placebo-Controlled;
                          Multicenter; Drug Tolerance
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Combination drug therapy.
PROTOCOL DETAILS          ACTUAL ACCRUAL: 337 (940511).
PROTOCOL DETAILS          STUDY DURATION: 1-2 years.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 40 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Asymptomatic HIV infection. 2. CD4
                          count 200-400 cells/mm3. 3. No HIV-associated
                          neurologic abnormalities or constitutional
                          symptoms. 4. No oral hairy leukoplakia. 5. At
                          least 6 months of prior AZT or at least 4
                          weeks of prior d4T or ddI OR prior
                          combination therapy with AZT/ddI or AZT/ddC.
                          [Refer to Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   HEMOGLOBIN: >= 11 g/dl. (men); >= 10 g/dl
                          (women).
PATIENT INCLUSION CRIT.   PLATELET COUNT: >= 75000 platelets/mm3.
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: 200 - 400 cells/mm3. (
                          200 - 300 - 400 ).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 5 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   KARNOFSKY: 100.
PATIENT INCLUSION CRIT.   OTHER: Absolute neutrophils >= 1000
                          cells/mm3. Total serum or pancreatic amylase
                          <= 2 x ULN.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Not
                          breast-feeding.
OTHER PATIENT INCL. CH.   PRIOR MEDICATION: Required: Prior AZT (>= 300
                          mg/day) for at least 6 months OR prior
                          didanosine (minimum 300 mg/day if > 45 kg or
                          200 mg/day if <= 45 kg) for at least 4 weeks
                          OR d4T (minimum 30 mg/day) for at least 4
                          weeks. Allowed: Prior ddC (minimum 1.125
                          mg/day) for at least 4 weeks, if given in
                          combination with AZT.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded: 1.
                          Herpes zoster (within the past 2 years). 2.
                          Oral candidiasis (confirmed). 3. Vulvovaginal
                          candidiasis (persistent, frequent, or poorly
                          responsive to therapy). 4. Bacillary
                          angiomatosis. 5. Listeriosis. 6. Idiopathic
                          thrombocytopenia purpura. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant.
                          Breast-feeding.
PATIENT EXCLUSION CRIT.   RISK BEHAVIOR: Significant active alcohol or
                          drug abuse.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded at any time prior
                          to study entry: More than one dose of
                          thymopentin. Excluded within 30 days prior to
                          study entry: 1. HIV vaccines. 2.
                          Investigational or non-FDA approved
                          medication. 3. Immunomodulatory therapies. 4.
                          Experimental therapies. 5. Any antiretroviral
                          therapy other than AZT, ddI, ddC, or d4T.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1. HIV
                          vaccines. 2. Investigational or non-FDA
                          approved medication. 3. Immunomodulatory
                          therapies. 4. Experimental therapies. 5. Any
                          antiretroviral therapy other than AZT, ddI,
                          ddC, d4T.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Abnormal chest x-ray, consistent with active
                          opportunistic infection. 2. Hypersensitivity
                          to thymopentin. 3. Significant chronic
                          underlying medical illness. 4. Grade 2 or
                          worse peripheral neuropathy.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0065  Thymopentin
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0004  Zidovudine
SUBSTANCE IDENTIFICATION  Drug 3  DRG-0016  Didanosine
SUBSTANCE IDENTIFICATION  Drug 4  DRG-0015  Dideoxycytidine
SUBSTANCE IDENTIFICATION  Drug 5  DRG-0043  Stavudine
TRADE NAME OF SUBSTANCE   Drug 1 Timunox
MANUFACTURERS             Drug 1: Immunobiology Research Institute
                          Route 22 East PO Box 999 Annandale, NJ
                          08801-0999 Contact: Linda Meyerson (908)
                          730-1750.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 3: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 4: Drugs are provided by each
                          participating unit site.
MANUFACTURERS             Drug 5: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 2: Minimum 300 mg/day.
                          Drug 3: At least 300 mg/day (if > 45 kg) or
                          200 mg/day (if <= 4Drug 4: At least 1.125
                          mg/day. Drug 5: Minimum 30 mg/day
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Subcutaneous (SC)
OTHER TREATMENT INFO.     END POINT: Disease progression, death.
SUPPORTING AGENCY         Immunobiology Research Institute.
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Didanosine/*THERAPEUTIC USE
MESH HEADING              Drug Therapy, Combination
MESH HEADING              Female
MESH HEADING              HIV Infections/*DRUG THERAPY
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Stavudine/*THERAPEUTIC USE
MESH HEADING              Thymopentin/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Zalcitabine/*THERAPEUTIC USE
MESH HEADING              Zidovudine/*THERAPEUTIC USE
CAS REGISTRY NUMBER       30516-87-1 (Zidovudine)
CAS REGISTRY NUMBER       3056-17-5 (Stavudine)
CAS REGISTRY NUMBER       69558-55-0 (Thymopentin)
CAS REGISTRY NUMBER       69655-05-6 (Didanosine)
CAS REGISTRY NUMBER       7481-89-2 (Zalcitabine)
LAST REVISION DATE        940511
ENTRY MONTH               9312
CALIFORNIA                Harbor UCLA Medical Center 1124 West Carson
                          Street / N24 Clinic Torrance, CA 90502
                          Contact: Dena Duran (310) 222-3848 OPEN
                          931207.
CALIFORNIA                Olive View Medical Center / Department of
                          Medicine 14445 Olive View Drive / 2B182 Olive
                          View Medical Center Sylmar, CA 91342 Contact:
                          Betsy Manchester (818) 364-3205 OPEN 931215
                          ACTU: 0602.
CALIFORNIA                Pacific Oaks Medical Group 4940 Van Nuys
                          Boulevard 2nd Floor Sherman Oaks, CA 91403
                          Contact: Neil Albright (818) 906-6279 OPEN
                          931217.
CALIFORNIA                HIV Research Group 458 26th Street San Diego,
                          CA 92102 Contact: Karen Sova (619) 544-0482
                          Contact: Dr Daniel Pearce (619) 544-0482 OPEN
                          931207.
CALIFORNIA                ACRC AIDS Community Research Consortium 1048
                          El Camino Real / Suite A Redwood City, CA
                          94063 Contact: Deborah Harriss (415) 364-6564
                          OPEN 931215.
CALIFORNIA                Conant Medical Group C/O Clinical Research
                          1635 Divisadero Street / Suite 606 San
                          Francisco, CA 94115 Contact: Tanya Kocian
                          (415) 923-1333 Contact: (415) 661-2613
                          Contact: (415) 923-0222 OPEN 931215.
CALIFORNIA                Dr Jeffrey Fessel Kaiser-Permanente 2200
                          O'Farrell San Francisco, CA 94115 Contact:
                          Gretchen VanRaalte (415) 202-3480 OPEN
                          940511.
CONNECTICUT               Dr Gary Blick 25 Valley Drive / Suite 200B
                          Greenwich, CT 06830 Contact: Julie Calo (203)
                          622-1118 OPEN 931207.
DISTRICT OF COLUMBIA      Dr Larry Bruni 801 Pennsylvannia Avenue /
                          Suite 201 Washington, DC 20003 Contact: Dr
                          Larry Bruni (202) 546-0796 OPEN 931207.
FLORIDA                   Stratogen 300 Arthur Godrey Road / Suite 200
                          Miami Beach, FL 33140 Contact: Brenda
                          Haliburton-Jones (305) 538-1400 OPEN 931207.
FLORIDA                   Community Research Initiative 1508 San
                          Ignacio Avenue / Suite 200 Coral Gables, FL
                          33146 Contact: John Cochrane (305) 661-1150
                          Contact: Rick Siclari (305) 667-9296 OPEN
                          931207.
FLORIDA                   Stratogen Health of Ft Lauderdale 800 E
                          Cypress Creek Road Suite 400 Ft Lauderdale,
                          FL 33334 Contact: Dr Gary Morey (305)
                          938-7000 Contact: Patty Easley (305) 938-7000
                          OPEN 940511.
FLORIDA                   Dr Bienvenido Yangco 4600 North Habana Avenue
                          / Suite 14 Tampa, FL 33614 Contact: Vicki
                          Kenyon (813) 870-4760 Contact: Dr Bienvenido
                          Yangco (813) 870-4759 OPEN 931207.
GEORGIA                   West Paces Medical Center 3193 Howell Mill
                          Road Suite 306 Atlanta, GA 30327 Contact: Kim
                          Cole (404) 350-5714 Contact: Dr. Steven
                          Marlowe (404) 350-5690 OPEN 940511.
ILLINOIS                  Northwestern University / Dept of Infectious
                          Diseases 303 East Superior / Room 828
                          Chicago, IL 60611 Contact: Pam Donath (312)
                          908-0949 OPEN 931207.
ILLINOIS                  Rush-Presbyterian St Luke's Medical Center
                          600 South Paulina 143 ACFAC Chicago, IL 60612
                          Contact: Michelle Agnoli (312) 942-5865 OPEN
                          931207.
INDIANA                   Indiana U School of Medicine / Department of
                          Infectious Dis 545 Barnhill Dr / Emerson Hall
                          / Rm 435 Indianapolis, IN 46202-5124 Contact:
                          Beth Zwickl (317) 274-8456 Contact: Heather
                          Nixon (317) 274-8456 OPEN 931207.
KANSAS                    Univ of Kansas School of Medicine - Wichita /
                          Clinical Rsch 1010 North Kansas Wichita, KS
                          67214-3199 Contact: Dal Harrison (316)
                          261-2855 OPEN 931207.
MASSACHUSETTS             Community Research Initiative of New England
                          320 Washington Street / 3rd Floor Brookline,
                          MA 02146 Contact: Jeanne Day (617) 566-4004
                          OPEN 931207.
MISSOURI                  Systemic Mycoses Pathogen Study Group Wash
                          Univ Sch of Med / 4511 Forest Park Pkwy /
                          Suite 304 St Louis, MO 63108 Contact: Michael
                          Klebert (314) 454-0058 Contact: Mike Conklin
                          (314) 454-0058 OPEN 931207.
MISSOURI                  Kansas City AIDS Research Consortium 2411
                          Holmes Blue IV Kansas City, MO 64108-2792
                          Contact: Gary R. Johnson (816) 235-5366
                          Contact: Dr. Lawrence Dall (816) 235-1964
                          OPEN 940511.
NEW YORK                  Dr David DiPietro 369 8th Avenue New York, NY
                          10001 Contact: Phyllis Ristau (212) 929-2530
                          OPEN 931207.
NEW YORK                  Dr Howard A Grossman 285 West 11th Street /
                          Suite 1-W New York, NY 10014 Contact: George
                          Theodore (212) 929-2629 OPEN 931207.
NEW YORK                  Dr Patrick Hennessey 650 First Avenue New
                          York, NY 10016 Contact: Kevin Gehan (212)
                          683-6470 OPEN 931207.
NEW YORK                  New York Hospital / Cornell Clinical Trials
                          525 East 68th Street / Baker 24 / Box 566 New
                          York, NY 10021 Contact: Trisha Sarracco (212)
                          746-4161 Contact: Jim Mahoney (212) 746-4160
                          OPEN 931216.
NEW YORK                  Van Etten Hospital / Bronx Municipal Hospital
                          Center Pelham Parkway South and Eastchester
                          Roads / Suite 607 Bronx, NY 10461 Contact:
                          Sylvia Perkins (718) 918-3670 OPEN 931207.
NEW YORK                  Long Island Jewish Medical Center 269-11 76th
                          Avenue / Division of Hematological Oncology
                          New Hyde Park, NY 11042 Contact: Eileen Fusco
                          (718) 470-7698 Contact: Dr Frederick Siegal
                          (718) 470-8938 OPEN 931207.
NEW YORK                  SUNY Stony Brook / Division of Infectious
                          Diseases HSC-T15 / Room 080 Stony Brook, NY
                          11794-8153 Contact: Ruthann Burke (516)
                          444-1658 OPEN 931207.
OHIO                      Cleveland Clinic / Dept of Rheumatic and
                          Immunologic Dis Desk A-50 / 9500 Euclid
                          Avenue Cleveland, OH 44106 Contact: Carol
                          Tuggle (216) 444-5258 OPEN 931207.
OREGON                    Dr Joel Godbey 220 Northeast Multinomah /
                          Suite 200 Portland, OR 97232 Contact: Joel
                          Godbey (503) 230-8770 CLOSED 940511.
OTHER                     Initiativa Comunitaria de Investigacion PO
                          Box 774 / Old San Juan Station San Juan, PR
                          00902 Contact: Dr Hermes Garcia (809)
                          250-8629 Contact: Dr.
PENNSYLVANIA              Novum Inc 5900 Penn Avenue Pittsburgh, PA
                          15206 Contact: Sharon Grace (412) 363-3300
                          OPEN 931207.
PENNSYLVANIA              Philadelphia FIGHT 201 North Broad Street /
                          6th Floor Philadelphia, PA 19107 Contact:
                          Carol Graeber (215) 557-8265 OPEN 931207.
PENNSYLVANIA              Graduate Hospital / Pepper Pavilion 18th and
                          Lombard Streets / Suite 505 Philadelphia, PA
                          19146 Contact: Shawn Sheeron (215) 893-2714
                          OPEN 931207.
 
157
UNIQUE IDENTIFIER         FDA/00586
PROTOCOL ID NUMBERS       FDA 012R
PROTOCOL TITLE            A Double-Blind, Placebo-Controlled Study of
                          Fluconazole in the Prevention of Active
                          Coccidioidomycosis and Other Systemic Fungal
                          Infections in HIV-Infected Patients Living in
                          the Coccidioidal Endemic Area.
VERSION NUMBER & DATE     (940104)
TRIAL CATEGORY            Opportunistic Infections
TRIAL CATEGORY            Asymptomatic
GENERAL DESCRIPTION       PURPOSE: To compare the efficacy of
                          fluconazole (200 mg daily) versus placebo in
                          preventing the development of active
                          coccidioidomycosis and other systemic fungal
                          infections among HIV-infected patients with
                          CD4 lymphocyte counts < 250 cells/mm3 who are
                          living in the coccidioidal endemic area.
                          Methodology: Patients are randomized to
                          receive either fluconazole or placebo daily
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive either fluconazole or placebo daily
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940413)
DISEASE STUDIED           Coccidioidomycosis, Fungal infections
                          (Mycoses).
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. HIV infection documented by
                          ELISA confirmed by Western blot. 2. CD4 count
                          < 250 cells/mm3. 3. No active
                          coccidioidomycosis or other fungal disease
                          requiring systemic antifungal therapy. 4.
                          Residence in area considered to be endemic
                          for Coccidioides immitis.
ELIGIBILITY               ASYM. ARC. AIDS.
OTHER PROTOCOL NUMBERS    R-0266
STUDY DESIGN              Double-Blind; Placebo-Controlled; Randomized;
                          2-Arm
PROTOCOL DETAILS          STUDY INTENT: Drug prophylaxis, Drug
                          efficacy.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 3 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. Documented HIV infection. 2. CD4
                          count < 250 cells/mm3. 3. No active
                          coccidioidomycosis or other fungal disease
                          requiring systemic antifungal therapy. 4.
                          Residence in area considered to be endemic
                          for Coccidioides immitis. 5. Consent of
                          parent or guardian if under legal age of
                          consent. [Refer to Laboratory values for
                          additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: < 250 cells/mm3. ( 0 -
                          100 - 200 ).
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 2 x ULN mg/dl. (ULN = upper
                          limit of normal).
PATIENT INCLUSION CRIT.   SGOT(AST): <= 7 x ULN.
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 7 x ULN.
PATIENT INCLUSION CRIT.   CREATININE: <= 2.0 mg/dl.
PATIENT INCLUSION CRIT.   CREATININE CLEARENCE: > 65 ml/min. (If
                          creatinine value unavailable).
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 7 x ULN.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test within 2 days of study entry.
                          Not breast-feeding. Abstinence or effective
                          method of birth control / contraception
                          including oral contraceptives during the
                          study.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          History of hypersensitivity to azole or
                          imidazole compounds. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test within 2 days of study entry.
                          Breast-feeding. No abstinence or no agreement
                          to use effective method of birth control /
                          contraception during the study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Systemic
                          antifungal agents within 2 weeks prior to
                          study entry.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: Systemic
                          antifungal therapy.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          symptoms or conditions are excluded: 1.
                          Unable to take oral medication. 2. Positive
                          serum cryptococcal antigen.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0005  Fluconazole
TRADE NAME OF SUBSTANCE   Drug 1 Diflucan
MANUFACTURERS             Drug 1: Pfizer Incorporated / Roerig Division
                          235 East 42nd Street New York, NY 10017-7851
                          Contact: Professional Information (212)
                          573-2187.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 200 mg (or placebo)
                          daily
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 200 mg (or placebo)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral
SUPPORTING AGENCY         Pfizer Incorporated / Roerig Division.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Coccidioidomycosis/COMPLICATIONS/*PREVENTION
                          & CONTROL
MESH HEADING              Female
MESH HEADING              Fluconazole/*THERAPEUTIC USE
MESH HEADING              HIV Infections/*COMPLICATIONS
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycoses/COMPLICATIONS/*PREVENTION & CONTROL
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        940413
ENTRY MONTH               9401
ARIZONA                   McDowell Clinic 1314 East McDowell Road
                          Phoenix, AZ 85006 Contact: Mary Coburn (602)
                          257-0606 OPEN 940104.
ARIZONA                   Veterans Administration Medical Center 3601 S
                          Sixth Avenue Tucson, AZ 85723 Contact: Kathy
                          Delgado (602) 792-1450 X 664OPEN 940104.
CALIFORNIA                Dr Lawrence Cone 3900 Bob Hope Drive / Probst
                          Bldg Rancho Mirage, CA 92270 Contact: Connie
                          Dzekov (619) 346-5688 OPEN 940104.
 
158
UNIQUE IDENTIFIER         FDA/00587
PROTOCOL ID NUMBERS       FDA 012Q
PROTOCOL TITLE            Comparative Randomized Study of the Efficacy,
                          Safety, and Toleration of Fluconazole Oral
                          Suspension or Nystatin Oral Suspension in the
                          Treatment of Patients With Oropharyngeal
                          Candidiasis in Association With the Acquired
                          Immunodeficiency Syndrome.
VERSION NUMBER & DATE     (940104)
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: To compare the efficacy, safety, and
                          toleration of fluconazole as a single daily
                          oral suspension (100 mg) for 14 days versus
                          nystatin oral suspension (500000 units) four
                          times daily for 14 days in the treatment of
                          oropharyngeal candidiasis in patients with
                          AIDS or HIV infection. Methodology: Patients
                          are randomized to receive 100 mg fluconazole
                          oral suspension once daily (swallowed at
                          approximately the same time every day) for 14
                          days OR 500000 units nystatin oral suspension
                          used to rinse the mouth four times daily for
                          14 days. No food or drink is permitted
                          immediately following the administration of
                          the nystatin
GENERAL DESCRIPTION       METHODOLOGY: Patients are randomized to
                          receive 100 mg fluconazole oral suspension
                          once daily (swallowed at approximately the
                          same time every day) for 14 days OR 500000
                          units nystatin oral suspension used to rinse
                          the mouth four times daily for 14 days. No
                          food or drink is permitted immediately
                          following the administration of the nystatin
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940104)
DISEASE STUDIED           Candidiasis, oropharyngeal.
DISEASES STATUS           Patients have the following symptoms and
                          conditions: 1. ARC or AIDS. 2. Signs of
                          oropharyngeal candidiasis (i.e., typical
                          white plaques) with some associated symptoms
                          (at minimum, presence of a sore mouth). 3.
                          Confirmation of diagnosis by presence of
                          pseudohyphae or hyphae forms identified from
                          swab or scraping obtained from a typical oral
                          lesion (culture specimens must be obtained
                          within 48 hours prior to study entry). NOTE:
                          Patients with signs or symptoms of
                          esophagitis (e.g., odynophagia) are not
                          eligible unless esophagoscopy is performed
                          and results are negative.
ELIGIBILITY               ARC. AIDS.
OTHER PROTOCOL NUMBERS    R-0223
STUDY DESIGN              2-Arm; Randomized; Comparative; Drug
                          Comparison; Prospective
PROTOCOL DETAILS          STUDY INTENT: Drug efficacy, Drug safety,
                          Drug tolerance, Comparative drug therapy,
                          Comparative toxicity.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 5 units.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: Patients must
                          have: 1. ARC or AIDS. 2. Signs of
                          oropharyngeal candidiasis (i.e., typical
                          white plaques) with some associated symptoms.
                          3. Confirmation of diagnosis by microscopic
                          exam and culture of organism. 4. Life
                          expectancy of at least 4 weeks. NOTE:
                          Patients with signs or symptoms of
                          esophagitis (e.g., odynophagia) are not
                          eligible unless esophagoscopy is performed
                          and results are negative. [Refer to
                          Laboratory values for additional
                          requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT INCLUSION CRIT.   BILIRUBIN: <= 3 mg/dl.
PATIENT INCLUSION CRIT.   SGOT(AST): <= 3 x ULN. (ULN = upper limit of
                          normal).
PATIENT INCLUSION CRIT.   SGPT(ALT): <= 3 x ULN.
PATIENT INCLUSION CRIT.   OTHER: Alkaline phosphatase <= 3 x ULN.
                          Prothrombin time <= 5 sec over control.
PATIENT AGE               AGE: 13 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Not pregnant. Negative
                          pregnancy test. Not breast-feeding.
                          Abstinence or effective method of birth
                          control / contraception including oral
                          contraceptives during the study.
OTHER PATIENT INCL. CH.   CONCURRENT MEDICATION: Allowed: 1. Phenytoin.
                          2. Oral hypoglycemics. 3. Coumarin-type
                          anticoagulants. 4. Cyclosporine.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: Patients with the
                          following prior conditions are excluded:
                          Known history of intolerance or allergy to
                          imidazoles or triazoles or the polyene
                          components of nystatin. [Refer to Laboratory
                          values for additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 12 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Pregnant. Positive
                          pregnancy test. Breast-feeding. No abstinence
                          or no agreement to use effective method of
                          birth control / contraception during the
                          study.
PATIENT EXCLUSION CRIT.   PRIOR MEDICATION: Excluded: Other antifungal
                          agents within the past 3 days.
PATIENT EXCLUSION CRIT.   CONCURRENT MEDICATION: Excluded: 1.
                          Antifungal agents other than study drugs. 2.
                          Other experimental medications.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: Patients with the following
                          conditions are excluded: 1. Unable to
                          tolerate oral medication. 2. Concurrent
                          enrollment on another experimental trial of
                          approved or non-approved drugs or systemic
                          compounds (without approval of Pfizer
                          clinical monitor).
PATIENT EXCLUSION CRIT.   AVAILABILITY: Unable or unwilling to be
                          followed at the same center for the conduct
                          of this study.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0005  Fluconazole
SUBSTANCE IDENTIFICATION  Drug 2  DRG-0064  Nystatin
TRADE NAME OF SUBSTANCE   Drug 1 Diflucan
MANUFACTURERS             Drug 1: Pfizer Incorporated / Roerig Division
                          235 East 42nd Street New York, NY 10017-7851
                          Contact: Professional Information (212)
                          573-2187.
MANUFACTURERS             Drug 2: Drugs are provided by each
                          participating unit site.
SUBSTANCE ADMIN. INFO.    DOSAGE SCHEDULE: Drug 1: 100 mg in oral
                          suspension swallowed once daily for 14 days
                          (loading dose of 200 mg given on day 1).
                          Daily dose in patwith renal impairment will
                          be 50 and 25 mg for estimated creaticlearance
                          of 21-50 and 11-20 ml/min, respectively. Drug
                          2: 500000 units (in 5 ml) used to rinse the
                          mouth QID
SUBSTANCE ADMIN. INFO.    DAILY DOSAGE: Drug 1: 100 mg (50 or 25 mg for
                          patients with renal impairment)Drug 2: 2
                          million units (in 20 ml)
SUBSTANCE ADMIN. INFO.    DELIVERY MODE: Drug 1: Oral. Drug 2: Oral
                          rinse
OTHER TREATMENT INFO.     TREATMENT DURATION: 14 days.
OTHER TREATMENT INFO.     DISCONTINUE: Patients discontinue treatment
                          for the following reason: Disease
                          progression.
SUPPORTING AGENCY         Pfizer Incorporated / Roerig Division.
MESH HEADING              AIDS-Related Complex/*COMPLICATIONS
MESH HEADING              Acquired Immunodeficiency Syndrome/
                          *COMPLICATIONS
MESH HEADING              Adolescence
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Candidiasis, Oral/COMPLICATIONS/*DRUG THERAPY
MESH HEADING              Female
MESH HEADING              Fluconazole/ADVERSE EFFECTS/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Nystatin/ADVERSE EFFECTS/*THERAPEUTIC USE
CAS REGISTRY NUMBER       1400-61-9 (Nystatin)
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        940104
ENTRY MONTH               9401
CALIFORNIA                California Medical Research Group 3636 North
                          First Street Fresno, CA 93726 Contact: Cathy
                          Good (209) 221-1317 OPEN 940104.
CALIFORNIA                University of California Hospital 521
                          Parnassus Avenue / Suite C-443 San Francisco,
                          CA 94143 Contact: Jackie Octavio (415)
                          476-9365 OPEN 940104.
MARYLAND                  The Johns Hopkins School of Medicine 1830
                          East Monument Street Baltimore, MD 21205
                          Contact: Karen Grimer (410) 955-1754 OPEN
                          940104.
PENNSYLVANIA              Medical College of Pennsylvania 3100 Henry
                          Avenue Philadelphia, PA 19129 Contact: Ken
                          Gebhart (215) 842-7444 OPEN 940104.
 
159
UNIQUE IDENTIFIER         FDA/00072
PROTOCOL ID NUMBERS       FDA 012C
PROTOCOL TITLE            Non-Comparative Study of Fluconazole in
                          Patients With Serious Mycoses and Who Cannot
                          Be Treated With Conventional Antifungal
                          Therapy.
TRIAL CATEGORY            Nationwide Access
TRIAL CATEGORY            Opportunistic Infections
GENERAL DESCRIPTION       PURPOSE: The primary purpose of this protocol
                          is to provide fluconazole for the treatment
                          of individual patients who require therapy
                          for serious or life-threatening systemic
                          fungal infection, who have failed on
                          conventional antifungal therapy or have had
                          unacceptable reactions to conventional
                          antifungal therapy, and who are ineligible
                          for other established fluconazole clinical
                          trial protocols.
OPEN/CLOSED INDICATOR     Open: Actively accruing patients (940413)
DISEASE STUDIED           Candidiasis, Fungal infections (Mycoses).
DISEASES STATUS           Patients with clinically established serious
                          or life-threatening systemic fungal disease
                          such as Candidiasis, cryptococcal infections,
                          histoplasmosis, blastomycosis,
                          coccidiomycosis, or paracoccidiomycosis will
                          be considered if conventional fungal therapy
                          is not an acceptable alternative. Clinically
                          established fungal disease is defined as the
                          presence of infection documented by culture,
                          histologic, or antigen detection methods.
                          Fungi include (but are not limited to)
                          Candida and candida-like organisms,
                          cyptococcus, histoplasmosis, blastomycosis,
                          ccidioidomycosis, and paracoccidioidomycosis.
ELIGIBILITY               OTHER. ARC. AIDS.
OTHER PROTOCOL NUMBERS    056-152
PROTOCOL DETAILS          STUDY INTENT: Compassionate use.
PROTOCOL DETAILS          NUMBER OF PARTICIPATING AGENCIES: 1 unit.
PATIENT INCLUSION CRIT.   GENERAL INCLUSION CRITERIA: AMENDED: 900207
                          Open only to unapproved indications and/or
                          age ranges. Original design: Patients with
                          clinically established serious or
                          life-threatening systemic fungal disease will
                          be considered if conventional fungal therapy
                          is not an acceptable alternative.
                          Unacceptability of conventional therapy is
                          defined as: o Failure of conventional therapy
                          to control or eradicate infection after
                          appropriate trial(s) of generally accepted
                          regimen(s). o Serious and unacceptable
                          untoward reaction(s) to conventional
                          antifungal therapy. OR A major
                          contraindication to the use of conventional
                          antifungal therapy. The patient must be
                          ineligible or have no access to other
                          established fluconazole investigational
                          protocols. The final judgment of patient
                          acceptability for inclusion lies with the
                          Pfizer Clinical Monitor. [Refer to Laboratory
                          values for additional requirements.]
PATIENT INCLUSION CRIT.   CD4 (T4 CELL) COUNT: Unspecified cells/mm3.
PATIENT AGE               AGE: 18 Years - 99 Years.
PATIENT SEX               MALE
PATIENT SEX               FEMALE
OTHER PATIENT INCL. CH.   REPRODUCTIVE CRITERIA: Unspecified.
PATIENT EXCLUSION CRIT.   GENERAL EXCLUSION CRITERIA: A patient will be
                          excluded if he/she has previously had an
                          unacceptable adverse effect due to
                          fluconazole. [Refer to Laboratory values for
                          additional requirements.]
PATIENT EXCLUSION CRIT.   AGE: 01 Days - 17 Years.
PATIENT EXCLUSION CRIT.   REPRODUCTIVE CRITERIA: Unspecified.
PATIENT EXCLUSION CRIT.   COMPLICATIONS: A patient will be excluded if
                          he/she has previously had an unacceptable
                          adverse effect due to fluconazole.
SUBSTANCE IDENTIFICATION  Drug 1  DRG-0005  Fluconazole
TRADE NAME OF SUBSTANCE   Drug 1 Diflucan
MANUFACTURERS             Drug 1: Pfizer Incorporated, Roerig Division
                          235 East 42nd Street New York, NY 10017-7851
                          Contact: Dr Perry Eisman (212) 573-7358.
SUPPORTING AGENCY         Pfizer, Incorporated.
MESH HEADING              Adult
MESH HEADING              Aged
MESH HEADING              Drugs, Investigational/THERAPEUTIC USE
MESH HEADING              Female
MESH HEADING              Fluconazole/*THERAPEUTIC USE
MESH HEADING              Human
MESH HEADING              Male
MESH HEADING              Middle Age
MESH HEADING              Mycoses/*DRUG THERAPY
CAS REGISTRY NUMBER       0 (Drugs, Investigational)
CAS REGISTRY NUMBER       86386-73-4 (Fluconazole)
LAST REVISION DATE        940413
ENTRY MONTH               8907
CONNECTICUT               Pfizer Central Research / USA Accrual Eastern
                          Point Road Groton, CT 06340 Contact: Pat
                          Robinson (203) 441-4812 OPEN 910326.
 
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