a phase i/ii study of recombinant interleukin-4 in aids and kaposi's sarcoma

Conditions: Sarcoma, Kaposi; HIV Infections

Summary: 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.

Eligibility criteria:
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.

Keywords: sarcoma, kaposi acquired immunodeficiency syndrome interleukin-4