The Safety of Zidovudine Plus Interferon-Alpha in HIV-Infected Children
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cook County Hosp. | Chicago | Illinois | United States | 60612 |
| 2 | Chicago Children's CRS | Chicago | Illinois | United States | 60614 |
| 3 | Tulane/LSU Maternal/Child CRS | New Orleans | Louisiana | United States | 70112 |
| 4 | BMC, Div. of Ped Infectious Diseases | Boston | Massachusetts | United States | 02118 |
| 5 | NYU Med. Ctr., Dept. of Medicine | New York | New York | United States | 10016 |
| 6 | St. Jude/UTHSC CRS | Memphis | Tennessee | United States | 38105 |
| 7 | Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds. | Bayamon | Puerto Rico | ||
| 8 | San Juan City Hosp. PR NICHD CRS | San Juan | Puerto Rico | 00936 | |
| 9 | Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS | San Juan | Puerto Rico | 00936 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Glaxo Wellcome
- Hoffmann-La Roche
Investigators
- Study Chair: Diaz C,
- Study Chair: Yogev R,
Study Documents (Full-Text)
None provided.More Information
Publications
- 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)
- ACTG 153
- 11128