biological therapy in treating children with refractory or recurrent neuroblastoma or other tumors

Conditions: Melanoma (Skin); Neuroblastoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Summary: rationale: biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing. purpose: phase i trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.

objectives: * determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other gd2-positive tumors. * determine the toxicity and pharmacokinetics of the fusion protein in these patients. * determine the effect of the fusion protein on systemic immune modulation in these patients. * quantitate the antifusion protein antibodies in patients treated with fusion protein. * evaluate antitumor responses resulting from this fusion protein regimen in these patients. outline: this is a dose-escalation study. patients receive hu14.18-interleukin-2 (hu14.18-il2) fusion protein iv over 4 hours once daily on days 1-3. treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of hu14.18-il2 fusion protein until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed every 2 months for 1 year, every 6 months for 3 years, and then annually for 5 years. projected accrual: a total of 18-24 patients will be accrued for this study within 1 year.

Eligibility criteria:
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

Keywords: metastatic osteosarcoma recurrent neuroblastoma recurrent osteosarcoma recurrent melanoma unspecified childhood solid tumor, protocol specific metastatic childhood soft tissue sarcoma recurrent childhood soft tissue sarcoma