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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.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000681
  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 I

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

Drug Information available for:   Zidovudine    Doxorubicin    Doxorubicin hydrochloride    Vincristine sulfate    Vincristine    Sargramostim    Granulocyte-macrophage colony-stimulating factor    Bleomycin    Bleomycin sulfate   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Open Label
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

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

Estimated Enrollment:   24

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000681

Locations
United States, California
UCLA CARE Ctr    
      Los Angeles, California, United States, 90095
Univ of Southern California / LA County USC Med Ctr    
      Los Angeles, California, United States, 900331079
K Norris Cancer Hosp / Los Angeles County - USC Med Ctr    
      Los Angeles, California, United States, 900331079
United States, District of Columbia
George Washington Univ Med Ctr    
      Washington, District of Columbia, United States, 20037
United States, Massachusetts
Beth Israel Deaconess - West Campus    
      Boston, Massachusetts, United States, 02215
United States, New York
SUNY / Erie County Med Ctr at Buffalo    
      Buffalo, New York, United States, 14215
United States, Pennsylvania
Presbyterian Univ Hosp / Univ of Pittsburgh    
      Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Investigators
Study Chair:     Gill PS    
Study Chair:     Miles S    
  More Information


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

Publications:

Study ID Numbers:   ACTG 094
First Received:   November 2, 1999
Last Updated:   August 7, 2008
ClinicalTrials.gov Identifier:   NCT00000681
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

Study placed in the following topic categories:
Sexually Transmitted Diseases, Viral
Malignant mesenchymal tumor
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
Vincristine
Zidovudine
Bleomycin
Doxorubicin
Soft tissue sarcomas
Immunologic Deficiency Syndromes
Herpesviridae Infections
Virus Diseases
Neoplasms, Connective and Soft Tissue
Kaposi sarcoma
HIV Infections
Sexually Transmitted Diseases
Sarcoma
DNA Virus Infections
Retroviridae Infections

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antibiotics, Antineoplastic
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Neoplasms, Vascular Tissue
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Neoplasms by Histologic Type
Anti-HIV Agents
Immune System Diseases
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Tubulin Modulators
Lentivirus Infections
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on December 03, 2008




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