RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein work in different ways to stimulate the immune system and stop tumor cells from growing. PURPOSE: This phase II trial is studying how well hu14.18-interleukin-2 fusion protein works in treating young patients with recurrent or refractory neuroblastoma.
OBJECTIVES: * Determine the response rate in children with recurrent or refractory neuroblastoma treated with hu14.18-interleukin-2 (hu14.18-IL2) fusion protein. * Determine the adverse events of this drug in these patients. * Determine the immunologic activation in patients treated with this drug. * Determine the induction of anti-hu14.18-IL2 antibody in patients treated with this drug. * Correlate antitumor response with measurements of toxicity, immune activation, and anti-hu14.18-IL2 antibody activity in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to measurable/evaluable disease (measurable by standard radiographic criteria vs evaluable by MIBG (meta-iodobenzylguanidine) scanning and/or bone marrow histology vs disease identified and quantified by bone marrow immunohistochemistry). For standard radiographic criteria this study will use the definitions of measurable disease from the Response Evaluation Criteria In Solid Tumors (RECIST) from the National Cancer Institute. Complete Response (CR) - Disappearance of all target lesions. No evidence of tumor at any site (chest, abdomen, liver, bone, bone marrow, nodes, etc). Very Good Partial Response (VGPR) - Greater than 90% decrease of the disease measurement for CT/MRI target lesions, taking as reference the disease measurement done to confirm measurable disease in target lesions at study entry; all pre-existing bone lesions with CR by MIBG; MIBG scan can be SD or CR in soft tissue lesions corresponding to lesions on CT/MRI. Partial Response (PR) - At least a 30% decrease in the disease measurement for CT/MRI target lesions, taking as reference the disease measurement done to confirm measurable disease in target lesions at study entry. Progressive Disease (PD) - Any one of the following: a) At least a 20% increase in the disease measurement for CT/MRI target lesions, taking as reference the smallest disease measurement recorded since the start of treatment. b) Appearance of one or more new lesions or new sites of tumor. c) PD as defined above for either bone marrow or MIBG lesions. Stable disease (SD) - The patient will be classified as stable disease for overall response if there is stable disease by either CT/MRI lesion, bone marrow, or MIBG criteria. No new lesions; no new sites of disease. Patients will be enrolled in 3 strata, and evaluated for antitumor response following 2 monthly courses (treatment on Days 1-3, followed by 25 days of observation,). Patients with progressive disease will be taken off protocol therapy. Patients with stabilization or regression of disease will be eligible to receive 2 more monthly courses of treatment. Additional treatment following course 4 will be allowed for patients showing a continued clinical response, up to a maximum of 10 courses of treatment. Patients are followed for survival. PROJECTED ACCRUAL: A total of 40-60 patients (20 for strata 1 and 2 and 0-20 for stratum 3) will be accrued for this study within 2 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Given IV
Number of Responders (Response Rate)
Response rate to hu14.18-Interleukin-2 in 3 separate strata of patients with recurrent or refractory neuroblastoma. Patients will have radiologic (CT/MRI) tumor and urine homovanillic acid (HVA)/vanillylmandelic acid (VMA) measurements. Patients with prior marrow involvement will have marrow assessments. Patients with MIBG+ (iodine-131-meta-iodobenzylguanidine) prior disease will have MIBG scans performed. For CT/MRI lesions, measureable disease is measured by the Response Evaluation Criteria In Solid Tumors (RECIST) from the National Cancer Institute. RECIST (v1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions.
Time frame: Up to 30 weeks
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