A Phase I Trial of Recombinant Human Interleukin-12 After High-Dose Therapy and Autologous Hematopoietic Stem Cell Support
A Phase I Trial of Recombinant Human Interleukin-12 After High-Dose Therapy and Autologous Hematopoietic Stem Cell Support
RATIONALE: Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells.
PURPOSE: Phase I trial to study the effectiveness of interleukin-12 in treating patients who have hematologic cancer or solid tumor.
OBJECTIVES: I. Assess the safety and maximum tolerated dose of interleukin-12 (IL-12) in patients with hematologic malignancies or solid tumors who have undergone high-dose chemotherapy and autologous stem cell transplantation. II. Evaluate the hematologic and immunologic effects of IL-12 in these patients.
OUTLINE: This is a dose-escalation study. Patients receive interleukin-12 (IL-12) IV as a single test dose followed by 2 weeks of rest. Patients then receive IL-12 IV daily for 5 days followed by 16 days of rest for up to 6 courses. Cohorts of 3-5 patients receive escalating doses of IL-12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 patients experience dose-limiting toxicity. Patients are followed until death.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically proven hematologic malignancies or solid tumors Undergone high-dose chemotherapy or chemoradiotherapy with autologous bone marrow and/or peripheral blood stem cell transplantation Confirmation of complete remission is required for acute leukemia No significant CNS disease No clinically significant ascites or pleural effusions Hormone receptor status: Not specified
PATIENT CHARACTERISTICS: Age: 18 and over Sex: Not specified Menopausal status: Not specified Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Hemoglobin at least 9 g/dL (transfusion allowed) Platelet count at least 50,000/mm3 (transfusion independent) No clinically significant coagulopathy (unless due to cancer and resolved) Hepatic: Bilirubin no greater than 2 mg/dL SGOT no greater than 2 times upper limit of normal No chronic or acute hepatitis Hepatitis B surface antigen negative Renal: Creatinine no greater than 2 mg/dL No symptomatic hypercalcemia Calcium less than 12 mg/dL Cardiovascular: No uncontrolled angina No arrhythmias requiring drug or device therapy No symptomatic congestive heart failure Pulmonary: No clinically significant pulmonary dysfunction Metabolic: No uncontrolled diabetes mellitus No untreated hyper or hypothyroidism No Cushing's disease Gastrointestinal: No clinically significant gastrointestinal hemorrhages No uncontrolled peptic ulcer disease No history of inflammatory bowel disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No serious infection requiring IV antibiotics No psychosis No clinically significant autoimmune disease HIV negative
PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent biologic therapy Chemotherapy: See Disease Characteristics Endocrine therapy: At least 3 weeks since prior corticosteroids No concurrent systemic corticosteroids (other than replacement doses) Radiotherapy: See Disease Characteristics Surgery: Not specified Other: No other concurrent investigational agents