A Phase I/II Study of Recombinant Interleukin-4 in AIDS and Kaposi's Sarcoma
A Phase I/II Study of Recombinant Interleukin-4 in AIDS and Kaposi's Sarcoma
To determine the safety and tolerance of interleukin-4 (IL-4) in patients with AIDS-related
 Kaposi's sarcoma. To determine the effects of IL-4 on tumor growth in patients with
 AIDS-related 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.
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.