A Phase I/II Pilot Study of Simultaneously Administered Rhu GM-CSF ( CHO Cell ) and Azidothymidine ( AZT ) in Patients With Severe HIV Infection and Leukopenia: Pharmacokinetics and Feasibility

A Phase I/II Pilot Study of Simultaneously Administered Rhu GM-CSF ( CHO Cell ) and Azidothymidine ( AZT ) in Patients With Severe HIV Infection and Leukopenia: Pharmacokinetics and Feasibility

To assess the safety and efficacy of subcutaneously administered sargramostim ( granulocyte-macrophage colony-stimulating factor; GM-CSF ) in increasing and maintaining the neutrophil count in HIV-infected adults who have developed neutropenia as a result of receiving the antiretroviral agent, zidovudine ( AZT ). To assess the safety and efficacy of subcutaneously administered GM-CSF in increasing and maintaining the neutrophil count in HIV-infected adults with pre-existing neutropenia who are at high risk of developing hematologic intolerance while receiving the antiretroviral agent, AZT, for the first time. To assess the potential therapeutic benefit of concomitant GM-CSF and AZT on the natural history of HIV infection and associated infectious complications.

Inclusion Criteria

Concurrent Treatment:

Allowed:

• Minimal local irradiation for tumors.

Patients must have:

• Diagnosis of AIDS or AIDS related complex (ARC).
• Neutropenia, due either to zidovudine (AZT) or HIV infection.
• Life expectancy = or > 6 months.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Significant malabsorption as defined by greater than 10 percent weight loss and one or more of the following:
• Serum carotene less than 75 IU/ml.
• Vitamin A level less than 75 IU/ml.
• More than 4 foul-smelling or greasy stools per day.
• Other criteria of malabsorption.
• Kaposi's sarcoma (KS) or other tumor which is likely to require specific antitumor therapy during study, other than minimal local irradiation.
• Active, life-threatening infection with bacterial, viral, fungal, or protozoan pathogens or fever of 39 degrees C within 10 days of study entry, unless it is apparent that the fever is not due to a severe underlying infection.

Concurrent Medication:

Excluded within 4 weeks of study entry:

• Any investigational drug.
• Immunomodulating agents.
• Hormonal therapy.
• Cytolytic chemotherapeutic agents.
• Antiretroviral agent other than zidovudine (AZT).
• Excluded within 4 months of study entry:
• Suramin.
• Excluded within 3 months of study entry:
• Ribavirin.

Patients with the following are excluded:

• Significant malabsorption.
• Tumor likely to require specific antitumor therapy during study.
• Other significant medical problems and conditions specified in Patient Exclusion Co-Existing Conditions.
• Uncorrected nutritional deficiencies that may contribute to neutropenia.
• Hypersensitivity to zidovudine (AZT) or other nucleoside analogs.
• Profound dementia or altered mental status that would prohibit the giving of informed consent.

Prior Treatment:

Excluded within 1 month of study entry:

• Transfusion.
• Excluded within 4 weeks of study entry:
• Radiation therapy to greater than 100 cm2 body area.

Current drug or alcohol abuse. Unprotected sexual behavior or other activities which might introduce a new inoculation of HIV during the study.

Patients must be willing to refrain from unprotected sexual or other activities which might introduce a new inoculum of HIV during the study.