The Safety of Zidovudine Plus Interferon-Alpha in HIV-Infected Children

This study has been completed.
Sponsor:
Collaborators:
Glaxo Wellcome
Hoffmann-La Roche
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000967
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

PRIMARY: To determine the maximum tolerated dose of interferon-alfa (IFN-A) alone and in combination with zidovudine (AZT); to assess the safety and tolerance of IFN-A alone and in combination with AZT.

SECONDARY: To evaluate the effect of combination IFN-A and AZT on immunologic and virologic parameters; to determine whether the pharmacokinetic parameters of AZT are modified by the subcutaneous administration of IFN-A.

AZT is effective in suppressing the progression of HIV infection in patients without symptoms or with AIDS or AIDS-related complex (ARC). However, use of AZT is limited by its frequent toxicity, which sometimes relates to the amount of drug given. Thus, a combination treatment of two drugs that work together may provide more effective and safer treatment. IFN-A is a drug that has antiviral effects and may work well with AZT.


Condition Intervention Phase
HIV Infections
Drug: Interferon alfa-2a
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Safety and Tolerance of Zidovudine and Interferon-Alpha in HIV-Infected Children

Resource links provided by NLM:


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

Estimated Enrollment: 52
Study Completion Date: September 1996
Detailed Description:

AZT is effective in suppressing the progression of HIV infection in patients without symptoms or with AIDS or AIDS-related complex (ARC). However, use of AZT is limited by its frequent toxicity, which sometimes relates to the amount of drug given. Thus, a combination treatment of two drugs that work together may provide more effective and safer treatment. IFN-A is a drug that has antiviral effects and may work well with AZT.

The study is being conducted in three stages. In Cohort A (IFN-A alone), four patients receive IFN-A; subsequent four-patient cohorts receive doses escalated in increments. If 50 percent or more of patients at any dose level experience grade 2 or better toxicity, doses in subsequent cohorts are escalated. If grade 3 or 4 toxicity is seen in one patient at a given dose level, two additional patients are enrolled at that level. Treatment is given subcutaneously (under the skin, with a needle), 3 times per week for 12 weeks. The MTD is defined as the dose level immediately below that at which 50 percent or more of patients experience grade 3 or 4 toxicity. In Cohort B (combination IFN-A plus AZT), patients who complete treatment in Cohort A continue on the same dose of IFN-A, and a low, middle, or high dose of AZT is added. In Cohort C, four newly assigned patients who have been on a stable prescribed dose of AZT of at least 90 mg/m2 for 6 weeks are treated at each of the same dose combinations as those in Cohort B. Treatment is given for 12 weeks. IFN-A is given subcutaneously 3 times a week and AZT is given orally every 6 hours. Dose levels of both drugs are increased until 50 percent or more of patients experience grade 3 or 4 toxicity in any dose level.

  Eligibility

Ages Eligible for Study:   3 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Recommended:

  • Prophylaxis for Pneumocystis carinii pneumonia.

Allowed:

  • Aerosol ribavirin for short-term treatment of acute respiratory syncytial virus (RSV).
  • Immunization according to the current recommendations of the Advisory Committee for Immunization Practice.
  • IVIG. Systemic ketoconazole, acyclovir, or oral nystatin for acute therapy.

Patients must have the following:

  • HIV infection. Patients with proven resistance to AZT are also eligible.

Prior Medication:

Allowed:

  • Aerosol ribavirin.

Required:

Cohort C treatment:

  • Stable prescribed dose of zidovudine (AZT) >= 90 mg/m2 for at least 6 weeks prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded: AIDS or class P-2B, D, or E symptomatic infection.

Concurrent Medication:

Excluded:

  • Hepatotoxic or neurotoxic drugs, immunosuppressants, or antiseizure medication. Ketoconazole, fluconazole, and acyclovir for prophylaxis. Immunomodulators (other than IVIG). Experimental drugs.

Cohort A patients:

  • AZT for clinical indications.

Prior Medication:

Excluded:

  • Other antiretroviral agents (including didanosine (ddI), dideoxycytidine (ddC), or soluble CD4) within 1 month of study entry. Systemic ribavirin administered for retroviral therapy within 2 months of study entry.
  • Immunomodulating agents including interferon, isoprinosine, interleukin-2, or lymphocyte transfusions within 4 weeks of study entry.
  • RBC transfusion within 4 weeks prior to study entry.

Alcohol or drug abuse.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000967

Locations
United States, Illinois
Chicago Children's CRS
Chicago, Illinois, United States, 60614
Cook County Hosp.
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
BMC, Div. of Ped Infectious Diseases
Boston, Massachusetts, United States, 02118
United States, New York
NYU Med. Ctr., Dept. of Medicine
New York, New York, United States, 10016
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 38105
Puerto Rico
Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.
Bayamon, Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Glaxo Wellcome
Hoffmann-La Roche
Investigators
Study Chair: Diaz C
Study Chair: Yogev R
  More Information

Additional Information:
Publications:
Diaz C, Yogev R, Culnane M, Rogers A, Van Dyke R, Fenton T. ACTG 153: a multicenter phase I study of alpha-interferon in HIV infected children. AIDS Clinical Trials Group. Int Conf AIDS. 1994 Aug 7-12;10(1):79 (abstract no 269B)
Clemente D, Yogev R, Culnane M, Rogers A, Van Dyke R, Hetherington S, Fenton T. ACTG 153: phase I, open-label; dose escalating study of interferon-alpha alone and in combination with zidovudine in children with early HIV disease. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:35

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000967     History of Changes
Other Study ID Numbers: ACTG 153, 11128
Study First Received: November 2, 1999
Last Updated: March 15, 2012
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
AIDS-Related Complex
Zidovudine
Interferon Type I

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
Interferon-alpha
Interferon Alfa-2a
Interferons
Zidovudine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014