A Phase I Study of the Combination of Recombinant GM-CSF, AZT, and Chemotherapy (ABV) (Adriamycin, Bleomycin, Vincristine) in AIDS and 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:
NCT00000681
First received: November 2, 1999
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Sarcoma, Kaposi
HIV Infections
Drug: Bleomycin sulfate
Drug: Vincristine sulfate
Drug: Doxorubicin hydrochloride
Drug: Zidovudine
Drug: Sargramostim
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of the Combination of Recombinant GM-CSF, AZT, and Chemotherapy (ABV) (Adriamycin, Bleomycin, Vincristine) in AIDS and Kaposi's Sarcoma

Resource links provided by NLM:


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

Estimated Enrollment: 24
Study Completion Date: October 1993
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.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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: NCT00000681

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
USC CRS
Los Angeles, California, United States, 900331079
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Investigators
Study Chair: Gill PS
Study Chair: Miles S
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000681     History of Changes
Other Study ID Numbers: ACTG 094, 11069
Study First Received: November 2, 1999
Last Updated: April 26, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vincristine
Doxorubicin
Drug Evaluation
Drug Therapy, Combination
Granulocyte-Macrophage Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Zidovudine
Bleomycin

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
Bleomycin
Doxorubicin
Liposomal doxorubicin
Vincristine
Zidovudine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 01, 2014