A Phase I/II Study of Recombinant Interleukin-4 in AIDS and Kaposi's Sarcoma

IL-4 exhibits a variety of beneficial effects on the immune system and is a potent inhibitor of Kaposi's sarcoma cells in vitro.

Patients are stratified into two groups according to CD4 count (less than 100 cells/mm3 and greater than or equal to 100 cells/mm3) and are enrolled in cohorts of four patients at each of four dose levels of IL-4 per stratum. Within each stratum, if patients at a given dose level have received at least 2 weeks of study therapy and no more than two patients experienced grade 3 or 4 drug-related toxicity, dose escalation in subsequent patients may begin. The MTD is defined as the dose at which 50 percent of patients develop grade 3 or worse toxicity. Patients with CD4 count less than 500 cells/mm3 (per 12/30/94 amendment) must be on antiretroviral therapy during study treatment.

PER AMENDMENT 11/20/95: Group I - enrollment is closed, the objective has been defined. Group II - patients must have CD4 cells greater than or equal to 100/mm3 and less than 500/mm3.

PER AMENDMENT 11/20/95: All patients will receive antiretroviral therapy.

Inclusion criteria

Concurrent Medication:

Required:

• Antiretroviral therapy during study treatment only in patients with CD4 count < 500 cells/mm3 (per 12/30/94 amendment).

Allowed:

• G-CSF for a second occurrence of grade 3 or 4 neutropenia (per 12/30/94 amendment).
• Nonsteroidal anti-inflammatory agents including acetaminophen for drug-related fevers.
• Systemic steroids for no more than 1 week in any 30-day period.
• PCP prophylaxis with TMP/SMX, dapsone, or inhaled pentamidine, if patient has a history of PCP or a CD4 count < 250 cells/mm3.

Allowed only in patients with CD4 count < 100 cells/mm3:

• Maintenance doses of ganciclovir, pyrimethamine/sulfa and TMP/SMX for stable, well-controlled opportunistic infections.
• Non-myelosuppressive treatment IND medications.

Prior Medication: Required: PER AMENDMENT 11/20/95:

• Stable dose of antiretroviral therapy required for at least 21 days prior to study entry for all patients. (Changed from - Stable dose of antiretroviral therapy for at least 21 days prior to study entry in patients with CD4 count < 500 cells/mm3 (per 12/30/94 amendment).

Patients must have:

• AIDS-related Kaposi's sarcoma.
• PER AMENDMENT 11/20/95: CD4 lymphocyte count >= 100 but < 500 cells/mm3. (Changed from - HIV infection.)
• PER AMENDMENT 11/20/95: All Patients will receive antiretroviral therapy. (Changed from - Current antiretroviral therapy IF CD4 count < 500 cells/mm3 (per 12/30/94 amendment).)
• No active opportunistic infections requiring induction therapy.
• Consent of parent or guardian if less than 18 years of age.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Other active malignancies (except basal cell carcinoma of the skin and in situ cervical cancer).
• Alteration in mental status that may prevent compliance.
• Cardiac functional capacity of Class II or worse OR regional wall abnormalities or abnormal ejection fraction on two-dimensional echocardiogram, if performed.

Concurrent Medication:

Excluded:

• Chemotherapy, interferons, or immune modulators for Kaposi's sarcoma.
• Myelosuppressive agents such as induction doses of ganciclovir, Fansidar (pyrimethamine/sulfadoxine), or any other investigational drugs (with the exception of non-myelosuppressive treatment IND medications in specific patients).
• GM-CSF or erythropoietin (except for a second grade 3/4 neutropenia or anemia).
• G-CSF.

Patients with the following prior conditions are excluded:

• History of myocardial infarction or significant arrhythmias.
• History of symptomatic hypoglycemia.

Prior Medication:

Excluded:

• Systemic therapy (including chemotherapy, interferons, and immune modulators) for Kaposi's sarcoma within 4 weeks prior to study entry.