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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001113
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  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 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.


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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


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

Estimated Enrollment: 48
Study Completion Date: March 1990
Detailed Description:

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001113

Locations
United States, New York
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Sponsors and Collaborators
Investigators
Study Chair: Krown S
  More Information

Additional Information:
Publications:
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)
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
Krown S, Bhalla R, Niedzwiecki D, Bundow D. Interferon (IFN), beta-2 microglobulin (beta2-m) and neopterin (Neo) in AIDS-associated Kaposi's sarcoma (KS). Int Conf AIDS. 1989 Jun 4-9;5:216 (abstract no ThBO28)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001113     History of Changes
Other Study ID Numbers: ACTG 014, 10990
Study First Received: November 2, 1999
Last Updated: March 15, 2012
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 Evaluation
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Interferon Type I

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
Sarcoma
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Interferon-alpha
Interferons
Zidovudine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antimetabolites

ClinicalTrials.gov processed this record on August 01, 2014