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

• Status: Completed
• Trial end date: 1993-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Bleomycin; Doxorubicin; Liposomal doxorubicin; Sargramostim; Vincristine; Zidovudine

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).