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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000967
• Other study ID #: ACTG 153
• Secondary ID: 11128
• Status: Completed
• Phase: Phase 1
• Est. completion date: September 1996

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 1996
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Interferon alfa-2a

• Zidovudine

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Glaxo Wellcome, Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

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

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)