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

Safety and Tolerance of Zidovudine and Interferon-Alpha in HIV-Infected Children

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Interferon alfa-2a

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.

• Study Type: Interventional
• Enrollment: 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico
    • Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.
  • San Juan, Puerto Rico, 00936
    • San Juan City Hosp. PR NICHD CRS
  • San Juan, Puerto Rico, 00936
    • Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp.
    • Chicago, Illinois, United States, 60614
      • Chicago Children's CRS
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane/LSU Maternal/Child CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • BMC, Div. of Ped Infectious Diseases
  • New York
    • New York, New York, United States, 10016
      • NYU Med. Ctr., Dept. of Medicine
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude/UTHSC CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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; Glaxo Wellcome
• Investigators: Study Chair: Diaz C; Study Chair: Yogev R

Publications and helpful links

General 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

Study record dates

Study Major Dates

• Study Completion (Actual): September 1, 1996

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 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; AIDS-Related Complex; Zidovudine; Interferon Type I
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; 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; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2; Zidovudine
• Other Study ID Numbers: ACTG 153; 11128 (Registry Identifier: DAIDS ES Registry Number)