A Phase I Study of AZT and Human Interferon Alpha (Recombinant Alpha-2A and Lymphoblastoid) in the Treatment of AIDS-Associated 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:
NCT00000725
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 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 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: 56
Study Completion Date: February 1990
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
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: NCT00000725

Locations
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
Sponsors and Collaborators
Investigators
Study Chair: Fischl MA
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000725     History of Changes
Other Study ID Numbers: ACTG 013, 10989
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 Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Interferon Type I

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
AIDS-Related Opportunistic Infections
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
Opportunistic Infections
Infection
Parasitic Diseases
Interferon-alpha
Interferons
Zidovudine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014