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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000725

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Kaposi HIV Infections	Drug: Interferon alfa-2a Drug: Zidovudine Drug: Interferon alfa-n1	Phase 1

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 Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Feb 1, 1990

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.