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

Phase 1
Completed
Conditions
HIV Infections
Registration Number
NCT00000967
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
52
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (9)

Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.

🇵🇷

Bayamon, Puerto Rico

St. Jude/UTHSC CRS

🇺🇸

Memphis, Tennessee, United States

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

Cook County Hosp.

🇺🇸

Chicago, Illinois, United States

Tulane/LSU Maternal/Child CRS

🇺🇸

New Orleans, Louisiana, United States

Chicago Children's CRS

🇺🇸

Chicago, Illinois, United States

NYU Med. Ctr., Dept. of Medicine

🇺🇸

New York, New York, United States

BMC, Div. of Ped Infectious Diseases

🇺🇸

Boston, Massachusetts, United States

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