Clinical trial NCT00002006: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Cytopenias
Keywords: Neutropenia
Drug Interactions
Granulocyte-Macrophage Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Zidovudine
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Natl Cancer Institute
state: Maryland
Study officials:
References:
citation: Levine JD, Allan JD, Tessitore JH, Falcone N, Galasso F, Israel RJ, Groopman JE. Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. Blood. 1991 Dec 15;78(12):3148-54.