PRIMARY: To determine safety, tolerance, and pharmacokinetics of zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) when given in combination in clinically stable AZT-treated children. SECONDARY: To compare combination therapy with mono drug therapy for antiviral activity and laboratory markers of disease progression, as determined by virologic and immunologic determinations. To evaluate the influence of combination therapy on disease progression as determined by evaluation of clinical criteria. In children currently being treated with AZT, it is unknown whether the addition of another antiretroviral agent such as ddC would help increase efficacy and tolerance. This study will examine the possible advantages of combination AZT/ddC therapy over monotherapy with AZT alone.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Zidovudine  Drug: Zalcitabine	Phase II

Further Study Details: 

Expected Total Enrollment:  180

In children currently being treated with AZT, it is unknown whether the addition of another antiretroviral agent such as ddC would help increase efficacy and tolerance. This study will examine the possible advantages of combination AZT/ddC therapy over monotherapy with AZT alone.

Patients are stratified according to duration of ongoing AZT therapy and are randomized to receive AZT either alone or in combination with ddC. Patients receive therapy until the last patient enrolled completes 32 weeks of therapy. The study may be extended for two additional 32-week periods on an optional basis.

Ages Eligible for Study:  3 Months   -   12 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Recommended:

• PCP prophylaxis.

Allowed:

• Intravenous and/or intramuscular immunoglobulin.
• Acyclovir (no more than 30 mg/kg/day PO).
• Ketoconazole (no more than 10 mg/kg/day).
• Nystatin.
• Aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs, sedatives, and barbiturates, not to exceed 72 hours.
• Isoniazid in combination with pyridoxine, provided there is no evidence of peripheral neuropathy.
• Trimethoprim / sulfamethoxazole.
• Amphotericin B (no more than 1 mg/kg for 5 days/week).
• Aerosolized ribavirin for bronchiolitis.
• Hematopoietic agents.
• Other drugs with little nephro-, hepato-, or cytotoxicity.
• Nutritional support for HIV wasting syndrome or malnutrition.

Patients must have:

• HIV infection.
• Ongoing stable AZT therapy.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms and conditions are excluded:

• Disease progression while on AZT, to the extent that the patient meets the criteria for advanced disease protocols.
• Known allergy or sensitivity to ddC.
• Cardiomyopathy.

Concurrent Medication: Excluded:

• Biologic modifiers other than IVIG, steroids, or hematopoietic agents.
• Investigational medications unless approved by protocol chair.
• Medications known to cause pancreatitis (unless ddC is interrupted while these medications are given).

Patients with the following prior conditions are excluded:

• History of intolerance or toxicity to AZT.
• History of symptomatic pancreatitis.
• History of peripheral neuropathy or abnormal nerve conduction velocity test.

Prior Medication: Excluded:

• Antiretroviral agents other than AZT within 2 weeks of study entry.

Required:

• Ongoing stable AZT therapy for more than 6 weeks duration.

Alabama
      Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham,  Alabama,  35294,  United States
California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
      San Francisco Gen Hosp, San Francisco,  California,  94110,  United States
      Stanford Univ School of Medicine / Pediatrics, Stanford,  California,  943054149,  United States
      Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles,  California,  905022004,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Cedars Sinai / UCLA Med Ctr, Los Angeles,  California,  900481804,  United States
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06504,  United States
      Univ of Connecticut / Farmington, Farmington,  Connecticut,  06032,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
      Children's Hosp of Washington DC, Washington,  District of Columbia,  200102916,  United States
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
Georgia
      Emory Univ Hosp / Pediatrics, Atlanta,  Georgia,  30306,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Univ of Illinois College of Medicine / Pediatrics, Chicago,  Illinois,  60612,  United States
      Univ of Chicago Children's Hosp, Chicago,  Illinois,  606371470,  United States
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Boston City Hosp / Pediatrics, Boston,  Massachusetts,  02118,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med School, Worcester,  Massachusetts,  016550001,  United States
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
New Jersey
      Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  071072198,  United States
      Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  07103,  United States
New York
      King's County Hosp Ctr / Pediatrics, Brooklyn,  New York,  11203,  United States
      SUNY - Brooklyn, Brooklyn,  New York,  11203,  United States
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      Westchester Hosp, Valhalla,  New York,  10595,  United States
      Schneider Children's Hosp, New Hyde Park,  New York,  11040,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      Mount Sinai Med Ctr / Pediatrics, New York,  New York,  10029,  United States
      Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States
      Metropolitan Hosp Ctr, New York,  New York,  10029,  United States
      Children's Hosp at Albany Med Ctr, Albany,  New York,  12208,  United States
      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States
      Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      Lincoln Hosp Ctr, Bronx,  New York,  10451,  United States
      Children's Hosp Pact Prog / Children's Hosp of Buffalo, Buffalo,  New York,  14222,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
Ohio
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
Pennsylvania
      Children's Hosp of Philadelphia, Philadelphia,  Pennsylvania,  191044318,  United States
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
Rhode Island
      Rhode Island Hosp / Brown Univ, Providence,  Rhode Island,  02903,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Canada, Ontario
      Sunnybrook Health Science Ctr, Toronto,  Ontario,  Canada
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico
      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00956,  Puerto Rico

Study chairs or principal investigators

S Pahwa,  Study Chair
SS Bakshi,  Study Chair

Study ID Numbers:  ACTG 190
Record last reviewed:  May 1995
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001032
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08