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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000725

Purpose

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	Intervention	Phase
Sarcoma, Kaposi HIV Infections	Drug: Interferon alfa-2a Drug: Zidovudine Drug: Interferon alfa-n1	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: AIDS Kaposi's Sarcoma Soft Tissue Sarcoma

Drug Information available for: Zidovudine Interferon alfa-2a Interferon alfa-n1 Interferons

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

56

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000725

Locations

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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Fischl MA

More Information

Additional Information:

Click here for more information about Zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about Interferon alfa-2a This link exits the ClinicalTrials.gov site

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. 1991;4(1):1-10.

Study ID Numbers:	ACTG 013
Study First Received:	November 2, 1999
Last Updated:	August 6, 2008
ClinicalTrials.gov Identifier:	NCT00000725 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Interferon Alfa-2a
Sarcoma, Kaposi
Dose-Response Relationship, Drug
Drug Therapy, Combination

Acquired Immunodeficiency Syndrome
Zidovudine
Interferon Type I

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Interferon Type I, Recombinant
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Zidovudine
Infection
Reverse Transcriptase Inhibitors
Neoplasms, Connective and Soft Tissue
Anti-Retroviral Agents
Therapeutic Uses

Neoplasms, Vascular Tissue
Growth Inhibitors
Angiogenesis Modulating Agents
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Interferon-alpha
RNA Virus Infections
Anti-HIV Agents
Neoplasms by Histologic Type
Immune System Diseases
Growth Substances
Sarcoma, Kaposi
Acquired Immunodeficiency Syndrome
Interferons
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 22, 2009