A Trial of Two Doses of 2',3'-Dideoxycytidine (ddC) in the Treatment of Children With Symptomatic HIV Infection Who Are Intolerant of AZT and/or Who Show Progressive Disease While on AZT

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zalcitabine

Detailed Description

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.

• Study Type: Interventional
• Enrollment: 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00619
    • Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.
  • San Juan, Puerto Rico
    • San Juan City Hosp. PR NICHD CRS
  • San Juan, Puerto Rico, 00936
    • Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
    • Oakland, California, United States, 94609
      • Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
    • San Diego, California, United States, 92093
      • UCSD Maternal, Child, and Adolescent HIV CRS
    • San Francisco, California, United States, 94143
      • UCSF Pediatric AIDS CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Med. Ctr., ACTU
  • Florida
    • Miami, Florida, United States, 33161
      • Univ. of Miami Ped. Perinatal HIV/AIDS CRS
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp.
    • Chicago, Illinois, United States, 60614
      • Chicago Children's CRS
    • Chicago, Illinois, United States, 60612
      • Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.
  • Louisiana
    • New Orleans, Louisiana, United States
      • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
    • New Orleans, Louisiana, United States
      • Tulane/LSU Maternal/Child CRS
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
    • Boston, Massachusetts, United States, 02118
      • BMC, Div. of Ped Infectious Diseases
    • Springfield, Massachusetts, United States, 01199
      • Baystate Health, Baystate Med. Ctr.
    • Worcester, Massachusetts, United States, 01655
      • WNE Maternal Pediatric Adolescent AIDS CRS
  • New Jersey
    • New Brunswick, New Jersey, United States
      • UMDNJ - Robert Wood Johnson
  • New York
    • Bronx, New York, United States, 10456
      • Bronx-Lebanon Hosp. IMPAACT CRS
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
    • Great Neck, New York, United States
      • North Shore-Long Island Jewish Health System, Dept. of Peds.
    • New Hyde Park, New York, United States, 11042
      • Schneider Children's Hosp., Div. of Infectious Diseases
    • New York, New York, United States, 10032
      • Columbia IMPAACT CRS
    • New York, New York, United States, 10037
      • Harlem Hosp. Ctr. NY NICHD CRS
    • New York, New York, United States, 10016
      • NYU Med. Ctr., Dept. of Medicine
    • New York, New York, United States, 10029
      • Metropolitan Hosp. NICHD CRS
    • Rochester, New York, United States, 14642
      • Univ. of Rochester ACTG CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases
    • Durham, North Carolina, United States, 27710
      • DUMC Ped. CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • St. Christopher's Hosp. for Children
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp. CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Hoffmann-La Roche
• Investigators: Study Chair: Spector SA

Publications and helpful links

General Publications

• Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7.
• Spector SA, Blanchard S, Connor EM, Salgo MP, McNamara J. Results of a clinical trial comparing two doses of 2'3'-dideoxycytidine (ddC) in the treatment of children with symptomatic human immunodeficiency virus (HIV) infection who were intolerant or had failed zidovudine (ZDV) therapy (ACTG 138). The Pediatric AIDS Clinical Trials Group. American Pediatric Society 104th annual meeting and Society for Pediatric Research 63rd annual meeting; 1994 May 2-5; Seattle. Pediatr AIDS HIV Infect. 1994 Oct;5(5):323 (unnumbered abstract)

Study record dates

Study Major Dates

• Study Completion (Actual): June 1, 1995

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 26, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Drug Evaluation; Zalcitabine
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Disease Progression; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zalcitabine
• Other Study ID Numbers: ACTG 138; 11113 (DAIDS ES Registry Number)