A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Date de début de l'étude : 1 octobre 2001

DISEASE CHARACTERISTICS: Histologically confirmed neuroblastoma or melanoma at original diagnosis Refractory to chemotherapy or recurrence after prior multiagent chemotherapy Measurable or evaluable (detectable by bone scan) metastatic disease OR No evidence of disease if complete response to prior surgical resection, radiotherapy, and/or chemotherapy OR Histologically confirmed tumor expressing GD2 antigen at original diagnosis or relapse Refractory to standard treatment Measurable or evaluable disease by clinical assessments or laboratory markers OR No evidence of disease after prior surgical resection of metastatic, recurrent disease Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy allowed Soft tissue sarcoma allowed No primary CNS tumors Prior CNS metastases allowed, provided: Disease previously treated Disease clinically stable for 4 weeks before study At least 4 weeks since prior steroids for CNS metastases No clinically detectable pleural effusions or ascites PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Karnofsky 60-100% for children over age 10 Lansky 60-100% for children age 10 and under Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count greater than 1,000/mm^3 Platelet count at least 75,000/mm^3 (transfusion allowed) Hemoglobin at least 9.0 g/dL (transfusion allowed) Hepatic: Bilirubin less than 1.5 mg/dL ALT or AST no greater than 2.5 times normal Hepatitis B surface antigen negative Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min Cardiovascular: Shortening fraction at least 27% by echocardiogram OR Ejection fraction more than 50% by MUGA scan No congestive heart failure No uncontrolled cardiac rhythm disturbance Pulmonary: FEV_1 and FVC more than 60% of predicted OR No dyspnea at rest No exercise intolerance Oxygen saturation more than 94% by pulse oximetry on room air Neurologic: No seizure disorders requiring antiseizure medications No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No significant concurrent illnesses unrelated to cancer or its treatment No significant psychiatric disabilities No uncontrolled active infections No uncontrolled active peptic ulcer PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior growth factors At least 1 week since prior immunomodulatory therapy Prior monoclonal antibodies allowed if no detectable antibody to hu14.18 Prior autologous bone marrow transplantation (BMT) or stem cell transplantation (SCT) allowed Prior autologous BMT or SCT with monoclonal antibody-purged specimens allowed No concurrent growth factors No concurrent interferon Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or melphalan) No concurrent palliative chemotherapy Endocrine therapy: See Disease Characteristics At least 2 weeks since prior glucocorticoids, except for life-threatening symptoms No concurrent corticosteroids No concurrent glucocorticoids, except for life-threatening symptoms Radiotherapy: See Disease Characteristics At least 3 weeks since prior radiotherapy No concurrent palliative radiotherapy Surgery: See Disease Characteristics At least 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy) No prior organ allografts No concurrent palliative surgery Other: Recovered from prior therapy At least 1 week since prior tretinoin At least 3 weeks since prior immunosuppressive therapy No other concurrent immunosuppressive drugs