To evaluate and compare the long-term (48-177 weeks) safety, tolerance, and efficacy of two doses of zalcitabine ( dideoxycytidine; ddC ) taken orally every 8 hours in children with symptomatic HIV infection who have one of the following: intolerance to zidovudine ( AZT ) (development of toxicity during prolonged AZT therapy), demonstrated disease progression after 6 months of AZT therapy, OR both AZT intolerance and disease progression after 6 months of AZT therapy. As useful as AZT appears to be in the treatment of patients infected with HIV, it is associated with significant toxicity in some patients, and it does not prevent ultimate progression to AIDS and eventual mortality. Thus, there is a clear need for new antiretroviral drugs, and ddC is one such promising agent.

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

Further Study Details: 

Expected Total Enrollment:  140

As useful as AZT appears to be in the treatment of patients infected with HIV, it is associated with significant toxicity in some patients, and it does not prevent ultimate progression to AIDS and eventual mortality. Thus, there is a clear need for new antiretroviral drugs, and ddC is one such promising agent.

Patients receive oral ddC for 48 to 177 weeks.

Ages Eligible for Study:  3 Months   -   18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Procrit.
• Amphotericin B (1 mg/kg up to 5 days/week).
• Prophylaxis treatment as per ACTG recommendations for Pneumocystis carinii pneumonia.
• Acyclovir (up to 1000 mg/day PO; for > 1000 mg/day PO or for any IV dose, suggest interrupting ddC).
• Ketoconazole (up to 10 mg/kg/day).
• Nystatin.
• Aspirin, acetaminophen, sedatives, and barbiturates (for up to 72 hours).
• Isoniazid (INH), if there is no evidence of peripheral neuropathy at entry. Children should receive pyridoxine, 25 - 50 mg/day to avoid possible INH-associated neuropathy.
• Trimethoprim / sulfamethoxazole (T/S).
• Immunoglobulin therapy.
• Aerosolized pentamidine.
• Drugs with little nephro-, hepato-, cytotoxicity that the patient has been taking and tolerating well for an ongoing condition.

Concurrent Treatment: Allowed:

• Immunoglobulin therapy.
• Nutritional support (for children with wasting syndrome and/or malnutritional) including hyperalimentation (TPN) of dietary supplements.

AMENDED:

• Patients enrolled in ACTG 051 may participate in ACTG 138 if they show intolerance to AZT or show disease progression after 6 months of AZT therapy and meet entry criteria for the study.

ORIGINAL design:

• Patients enrolled in ACTG protocols 051 or 128 must meet study end points or meet protocol definitions for being permanently off zidovudine (AZT) before enrolling in this protocol.

Patients must have the following:

• Absence of acute opportunistic infection at time of entry.
• However, if patient is successfully treated for opportunistic infection and has remained stable for 2 weeks after treatment, the patient is then allowed to enter the study. Children receiving maintenance therapy for > 4 weeks are eligible.
• Parent or guardian available to give written informed consent.

Allowed at time of study entry:

• Prophylaxis treatment as per ACTG recommendations, for Pneumocystis carinii pneumonia (PCP).
• Immunoglobulin therapy.

Prior Medication: AMENDED:

• AZT or ddI up until study entry, other antiretrovirals up until 4 weeks of study entry Allowed:
• Zidovudine (AZT) within 4 weeks of entry.
• Dideoxyinosine (ddI) within 43 weeks of entry if no peripheral neuropathy has been observed while receiving ddI.
• Other toxicities observed while on ddI must resolve to level 2 or better before patient can begin treatment with ddC.
• Vitamin, folate, iron supplements.

Exclusion Criteria

Co-existing Condition: AMENDED:

• 04-25-91 Additional excluded symptoms and conditions:
• Symptomatic cardiomyopathy.
• Seizures which are not well controlled by ongoing anticonvulsant therapy.
• Active malignancy requiring concomitant chemotherapy.
• Symptomatic pancreatitis.
• Grade I or greater peripheral neuropathy.
• Receiving concomitant zidovudine (AZT).
• Patients with the following conditions or symptoms are excluded:
• Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry.
• Known hypersensitivity to dideoxycytidine (ddC).

Concurrent Medication: Excluded:

• Other antiviral agents, biological modifiers, and investigational medications.
• Drugs with potential to cause peripheral neuropathy, including chloramphenicol, iodoquinol, phenytoin, ethionamide, gold, ribavirin, vincristine, cisplatin, dapsone, disulfiram, glutethimide, hydralazine, metronidazole, nitrofurantoin.

Patients with the following are excluded:

• Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry.
• Known hypersensitivity to dideoxycytidine (ddC).
• Active opportunistic infection requiring treatment with an excluded concomitant medication.

Prior Medication: Excluded:

• Antiretroviral agents (other than zidovudine (AZT) or didanosine (ddI)) within 4 weeks of entry.
• Immunomodulating agents such as interferons, isoprinosine, or interleukin-2 within 2 weeks of entry.
• Any other experimental therapy, drugs that cause prolonged neutropenia, significant nephrotoxicity, or peripheral neuropathy within 1 week of entry.

California
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
      Stanford Univ School of Medicine / Pediatrics, Stanford,  California,  943054149,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      Kaiser Permanente / UCLA Med Ctr, Downey,  California,  902422814,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Cedars Sinai / UCLA Med Ctr, Los Angeles,  California,  900481804,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
      Northern California Pediatric AIDS Treatment Ctr / UCSF, San Francisco,  California,  94143,  United States
Connecticut
      Univ of Connecticut Health Ctr / Pediatrics, Farmington,  Connecticut,  06032,  United States
District of Columbia
      Children's Hosp of Washington DC / Children's Natl Med Ctr, Washington,  District of Columbia,  20010,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
Georgia
      Emory Univ School of Medicine, Atlanta,  Georgia,  30303,  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, Chicago,  Illinois,  60612,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  212874933,  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 Ctr, Worcester,  Massachusetts,  01655,  United States
New Jersey
      Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  071072198,  United States
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Westchester Hosp, Valhalla,  New York,  10595,  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
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  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
      Metropolitan Hosp Ctr, New York,  New York,  10029,  United States
      Lincoln Hosp Ctr / Pediatrics, Bronx,  New York,  10451,  United States
      SUNY / Health Sciences Ctr at Brooklyn / Pediatrics, Brooklyn,  New York,  11203,  United States
      Northshore Hosp / Cornell Univ, Manhasset,  New York,  11030,  United States
      Schneider Children's Hosp / Long Island Jewish Med Ctr, New Hyde Park,  New York,  11042,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10456,  United States
      Beth Israel Med Ctr / Pediatrics, New York,  New York,  10003,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
Pennsylvania
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
Texas
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Puerto Rico
      UPR Children's Hosp / San Juan City Hosp, San Juan,  00936,  Puerto Rico
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00619,  Puerto Rico

Study chairs or principal investigators

Spector SA,  Study Chair

Study ID Numbers:  ACTG 138
Record last reviewed:  April 1996
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000653
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08