A Phase I Study of AZT and Human Interferon Alpha (Recombinant Alpha-2A and Lymphoblastoid) in the Treatment of AIDS-Associated Kaposi's Sarcoma

To evaluate the safety and toxicity of combination therapy for AIDS-associated Kaposi's sarcoma with zidovudine (AZT) and two kinds of interferon alpha. The two kinds are interferon alpha (IFN-A) and interferon alpha-2A (recombinant) (IFN-A2A). To define the pharmacokinetics of both AZT and IFN-A or IFN-A2A when given in combination; to define the maximum tolerated dose of each drug in combination and to define doses to be used in Phase II trials. AZT has been found to inhibit both the in vitro (in test tube) and cell killing effects of HIV, and both interferons (IFN-A and IFN-A2A) have shown antiviral and antitumor effect in Kaposi's sarcoma. It is reasonable to assume that a synergistic effect and enhanced antitumor response may be seen with combination therapy. A study to evaluate the safety and efficacy of AZT in combination with IFN-A or IFN-A2A is warranted.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Sarcoma, Kaposi
• Intervention / Treatment: Drug: Zidovudine; Drug: Interferon alfa-2a; Drug: Interferon alfa-n1

Detailed Description

AZT has been found to inhibit both the in vitro (in test tube) and cell killing effects of HIV, and both interferons (IFN-A and IFN-A2A) have shown antiviral and antitumor effect in Kaposi's sarcoma. It is reasonable to assume that a synergistic effect and enhanced antitumor response may be seen with combination therapy. A study to evaluate the safety and efficacy of AZT in combination with IFN-A or IFN-A2A is warranted.

Patients are randomized to receive IFN-A or IFN-A2A (given by intramuscular injection) and combined with AZT (taken orally) daily for 8 weeks. Study stops when maximum tolerated dose (MTD) is reached. Two cohorts of 4 patients enter each dose level. Patients do not enter into the next dose level until all patients have completed 3 weeks of treatment. AZT will escalate only if there is no unacceptable toxicity (grade 2 in = or > 3 patients or > grade 2 in any patient), subsequent increases in IFN-A or IFN-A2A will be permitted, but the AZT dose will remain fixed. The MTD for a given IFN-A or IFN-A2A dose level is defined as grade 2 toxicity (grade 3 for hemoglobin, neutrophil count, or SGOT) in 4 of the 6 patients. Patients have blood drawn every week and their general health is evaluated. Pharmacokinetic studies will be done on days 1, 21, and 24. Patients tolerating the combination may be continued on the same dose level for 1 year except if patient has reached complete remission for = or > 90 days, IFN-A or IFN-A2A will decrease to 3 times a week.

• Study Type: Interventional
• Enrollment: 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 331361013
      • Univ of Miami School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Patients must have biopsy-proven AIDS-associated Kaposi's sarcoma.
• Evidence of HIV infection as manifested by a positive antibody test.

Exclusion Criteria

• Active drug or alcohol abuse.

Co-existing Condition:

Excluded are patients with:

• Active opportunistic infections requiring ongoing therapy.
• Excluded within 90 days of study entry:
• Must be off therapy for Pneumocystis carinii pneumonia (PCP) unless recovered.
• Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia.
• Concurrent neoplasms other than basal cell carcinoma of the skin.
• Known hypersensitivity to polymycin B or neomycin.

Excluded are patients with:

• Active opportunistic infections requiring ongoing therapy.
• Excluded within 90 days of study entry:
• Must be off therapy for Pneumocystis carinii pneumonia (PCP) unless recovered.
• Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia.
• Concurrent neoplasms other than basal cell carcinoma of the skin.
• Known hypersensitivity to polymycin B or neomycin.

Prior Medication:

Excluded:

• Interferon.
• Zidovudine (AZT).
• Excluded within 30 days of study entry:
• Any biologic modifiers, corticosteroids, cytotoxic chemotherapeutic agents.
• Other drugs which can cause neutropenia or significant nephrotoxicity.
• Rifampin or rifampin derivatives, or systemic anti-infectives.
• Excluded within 90 days of study entry:
• Other antiviral agents.
• A history of Pneumocystis carinii pneumonia (PCP) completed treatment.

Prior Treatment:

Excluded within 30 days of study entry:

• Radiation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Fischl MA, Uttamchandani RB, Resnick L, Agarwal R, Fletcher MA, Patrone-Reese J, Dearmas L, Chidekel J, McCann M, Myers M. A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. J Acquir Immune Defic Syndr (1988). 1991;4(1):1-10.

Study record dates

Study Major Dates

• Study Completion (Actual): February 1, 1990

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): November 3, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; Zidovudine; Interferon Alfa-2a; Dose-Response Relationship, Drug; Sarcoma, Kaposi; Interferon Type I
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; DNA Virus Infections; Herpesviridae Infections; Neoplasms, Vascular Tissue; Sarcoma; Sarcoma, Kaposi; 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 013; 10989 (Registry Identifier: DAIDS ES Registry Number)