A Phase I Study of the Combination of Recombinant GM-CSF, AZT, and Chemotherapy (ABV) (Adriamycin, Bleomycin, Vincristine) in AIDS and Kaposi's Sarcoma

October 26, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine the safety as well as the most effective dose of sargramostim (GM-CSF; granulocyte-macrophage colony stimulating factor) that will prevent the side effects caused by the combined use of zidovudine (AZT) and various doses of cancer-fighting drugs (doxorubicin, bleomycin, and vincristine) in AIDS patients with Kaposi's sarcoma (KS).

Patients included in this study have KS, which is a type of cancer that occurs in nearly 20 percent of patients with AIDS. AIDS patients with extensive KS require treatment with effective cytotoxic (anti-cancer) agents to reduce the tumor size and with antiretroviral agents such as AZT to prevent or ameliorate the development of opportunistic infections. Due to the significant toxic effect of both cytotoxic and antiviral agents on the bone marrow where new blood cells are generated, the combination of these agents is expected to result in complications such as granulocytopenia (very low granulocyte counts). Hematopoietic growth factors such as GM-CSF may reduce the severity and duration of marrow suppression. This may improve survival. Clinical trials of GM-CSF in HIV infected individuals with or without granulocytopenia have shown that the progenitor cells (early blood cells) are responsive to GM-CSF.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients included in this study have KS, which is a type of cancer that occurs in nearly 20 percent of patients with AIDS. AIDS patients with extensive KS require treatment with effective cytotoxic (anti-cancer) agents to reduce the tumor size and with antiretroviral agents such as AZT to prevent or ameliorate the development of opportunistic infections. Due to the significant toxic effect of both cytotoxic and antiviral agents on the bone marrow where new blood cells are generated, the combination of these agents is expected to result in complications such as granulocytopenia (very low granulocyte counts). Hematopoietic growth factors such as GM-CSF may reduce the severity and duration of marrow suppression. This may improve survival. Clinical trials of GM-CSF in HIV infected individuals with or without granulocytopenia have shown that the progenitor cells (early blood cells) are responsive to GM-CSF.

AMENDED 910222 Due to continued concerns about GM-CSF toxicities seen in the 5 mcg/kg GM-CSF with 20 mg/m2 adriamycin/BV/AZT cohort, the GM-CSF dose in this study has been reduced while the adriamycin dose escalation will continue.

AMENDED 900430 Dosages for AZT and GM-CSF changed to reflect ongoing results. Original design: Patients receive the combination of AZT, antineoplastic chemotherapy, and GM-CSF in groups of three patients each. The first group receives baseline doses, and if the treatment is well tolerated, the subsequent groups of patients receive higher doses of the chemotherapy, in which the dose of doxorubicin is increased while bleomycin, vincristine, and AZT doses remain fixed throughout the study. The dose of all drugs remains fixed for a given patient. The anticancer drugs are given intravenously every 2 weeks. AZT is given every 4 hours by mouth. GM-CSF is self-injected subcutaneously every day from day 2 - day 12 of each treatment cycle. Patients repeat the chemotherapy every 2 weeks, for a maximum of seven cycles, with AZT being given continuously. When the maximum tolerated dose (MTD) of chemotherapy combined with GM-CSF is determined, the next phase of the study begins. Again the dose of chemotherapy is increased in groups of patients, but the every-day dose of GM-CSF is increased. Again, these chemotherapy cycles are repeated every 2 weeks up to a maximum of seven cycles. Patients receive physician examination and laboratory tests every week during the study and again at 4 weeks after the study. AMENDED: Dosages for AZT and GM-CSF have been changed to reflect ongoing results.

Study Type

Interventional

Enrollment

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Center CRS
      • Los Angeles, California, United States, 900331079
        • USC CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med. Ctr., ACTG CRS
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY - Buffalo, Erie County Medical Ctr.
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Non-steroidal agents such as acetaminophen for drug-related fevers.
  • Pentamidine inhalation prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients with a prior history or a T4 count < 200 cells/mm3.
  • Antiemetics for nausea, vomiting.
  • Symptomatic treatment for grades 1 and 2 oral toxicity.
  • Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).

Patients must have newly diagnosed biopsy-proven advanced AIDS-related Kaposi's sarcoma.

Exclusion Criteria

Concurrent Medication:

Excluded:

  • Systemic steroids for > 1 week in any 30 days.
  • All known marrow-suppressive agents.
  • Any other investigational drugs.

Patients will be excluded from the study for the following reasons:

  • The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer.
  • Alteration of mental status that may not permit compliance with the protocol.
  • Symptomatic sensory or motor neuropathy.
  • History of myocardial infarction or significant arrhythmias.
  • Class III/IV functional capacity in cardiac patients.

Prior Medication:

Excluded:

  • Cytotoxic chemotherapy.

Excluded within 1 week of study entry:

  • Therapy for Kaposi's sarcoma, including interferons, immunomodulators, antiretroviral agents.

Patients may not have any of the following diseases or symptoms:

  • Allergy to bleomycin.
  • The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer.
  • Alteration of mental status that may not permit compliance with the protocol.
  • Symptomatic sensory or motor neuropathy.
  • History of myocardial infarction or significant arrhythmias.
  • Class III/IV functional capacity in cardiac patients.
  • Concurrent serious infections, such as Pneumocystis carinii pneumonia (PCP), toxoplasma brain abscess, cytomegalovirus (CMV) retinitis or colitis, cryptococcal meningitis, and symptomatic Mycobacterium avium- intracellulare (MAI).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Miles S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

October 1, 1993

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 3, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 094
  • 11069 (DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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