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

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000653
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
HIV Infections
Drug: Zalcitabine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 140
Study Completion Date: June 1995
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.

  Eligibility

Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000653

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

Additional Information:
Publications:
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000653     History of Changes
Other Study ID Numbers: ACTG 138, 11113
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zalcitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 16, 2014