A Study of AZT Plus Human Interferon Alpha in the Treatment of AIDS-Related Kaposi's Sarcoma

NCT ID: NCT00001113

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1990-03-31

Brief Summary

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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 AZT and IFN-A or AZT and IFN-A2A when given in combination. To define the maximum tolerated dose (MTD) of each drug in combination and to define doses to be used in Phase II trial. AZT has been found to be effective against the effects of HIV in vitro (test tube) and both interferons have shown antiviral and antitumor effect on Kaposi's sarcoma. It is reasonable to assume that a synergism and an enhanced antitumor response may be seen with combination therapy. A study to evaluate the safety and effectiveness of AZT in the combination with IFN-A2A is warranted.

Detailed Description

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AZT has been found to be effective against the effects of HIV in vitro (test tube) and both interferons have shown antiviral and antitumor effect on Kaposi's sarcoma. It is reasonable to assume that a synergism and an enhanced antitumor response may be seen with combination therapy. A study to evaluate the safety and effectiveness of AZT in the combination with IFN-A2A is warranted.

Patients are randomized to receive IFN-A or IFN-A2A by intramuscular injection and combined with AZT orally daily for 8 weeks. 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 escalates only if there is no unacceptable toxicity (grade 2 in = or \> 3 patients or \> grade 2 in any patients); subsequent increase 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 3 toxicity for hemoglobin or grade 2 toxicity for other parameters in 3 of the 6 patients. Once the MTD is reached, there will be no further enrollment at higher dose level. Patients are followed every week for vital signs and hematologic studies. Patients tolerating the combination may be continued on therapy for 1 year at the same dose as the end of 8th week.

Conditions

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Sarcoma, Kaposi HIV Infections

Keywords

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Interferon Alfa-2a Sarcoma, Kaposi Dose-Response Relationship, Drug Drug Evaluation Drug Therapy, Combination Acquired Immunodeficiency Syndrome Zidovudine Interferon Type I

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Interferon alfa-2a

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Interferon alfa-n1

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient must have a histologically confirmed diagnosis of Kaposi's sarcoma.
* Positive antibody to HIV confirmed by ELISA or Western blot on the same serum.

Exclusion Criteria

* Active drug or alcohol abuse.

Co-existing Condition:

Patients with the following complications are excluded:

* Active opportunistic infections requiring ongoing therapy.
* Pneumocystis carinii pneumonia (PCP) unless recovered must be off therapy within 90 days prior to study.
* Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia.
* Concurrent neoplasms other than basal cell carcinoma of skin.
* Known sensitivity to polymycin or neomycin.

Patients with the following complications are excluded:

* Active opportunistic infections requiring ongoing therapy.
* Pneumocystis carinii pneumonia (PCP) unless recovered must be off therapy within 90 days prior to study.
* Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia.
* Concurrent neoplasms other than basal cell carcinoma of skin.
* Known sensitivity to polymycin or neomycin.

Prior Medication:

Excluded:

* Any prior zidovudine (AZT) or interferon alpha protocol participation.
* Excluded within 30 days of study entry:
* Immunomodulating agents.
* Other drugs that can cause neutropenia or significant nephrotoxicity, or systemic anti-infectives.
* Excluded within 90 days of study entry:
* Antiretroviral agents.
* Treatment of Pneumocystis carinii pneumonia (PCP).

Prior Treatment:

Excluded within 30 days of study entry:

* Radiation therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Krown S

Role: STUDY_CHAIR

Locations

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Mem Sloan - Kettering Cancer Ctr

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 1670585 (View on PubMed)

Berman E, Duigou-Osterndorf R, Krown SE, Fanucchi MP, Chou J, Hirsch MS, Clarkson BD, Chou TC. Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells. Blood. 1989 Sep;74(4):1281-6.

Reference Type BACKGROUND
PMID: 2765664 (View on PubMed)

Krown S, Bundow D, Gansbacher B, Gold J, Flomenberg N, Armstrong D. Interferon (IFN) alpha+ AZT in AIDS-associated Kaposi's sarcoma (KS): final results of a phase I trial. Int Conf AIDS. 1989 Jun 4-9;5:414 (abstract no WBP374)

Reference Type BACKGROUND

ICDB/88643799. Krown SE, et al. Interferon-alpha (IFN-alpha) plus zidovudine (ZDV) in AIDS-associated Kaposi's sarcoma (AIDS/KS): an ongoing phase I trial. Proc Annu Meet Am Soc Clin Oncol. 1988 7:A2

Reference Type BACKGROUND

Krown SE, Gold JW, Niedzwiecki D, Bundow D, Flomenberg N, Gansbacher B, Brew BJ. Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990 Jun 1;112(11):812-21. doi: 10.7326/0003-4819-112-11-812.

Reference Type BACKGROUND
PMID: 1971504 (View on PubMed)

Krown SE, Niedzwiecki D, Bhalla RB, Flomenberg N, Bundow D, Chapman D. Relationship and prognostic value of endogenous interferon-alpha, beta 2-microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS. J Acquir Immune Defic Syndr (1988). 1991;4(9):871-80.

Reference Type BACKGROUND
PMID: 1895208 (View on PubMed)

Other Identifiers

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10990

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 014

Identifier Type: -

Identifier Source: org_study_id