N2000-01: Double Infusion of Iodine I 131 Metaiodobenzylguanidine Followed by Autologous Stem Cell Transplantation
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Giving iodine I 131 metaiodobenzylguanidine (^131I-MIBG) may kill neuroblastoma
      cells by delivering radiation directly to the tumor. A stem cell transplant using the
      patient's stem cells may be able to replace blood-forming cells destroyed by radiation
      therapy.

      PURPOSE: This phase I trial is studying the side effects and best dose of a double infusion
      of ^131I-MIBG followed by autologous stem cell transplantation in treating patients with
      refractory neuroblastoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the maximum tolerated red marrow radiation dose delivered and associated toxic
           effects of escalating activity of iodine I 131 metaiodobenzylguanidine (^131I-MIBG)
           followed by autologous hematopoietic stem cell transplantation in patients with
           refractory neuroblastoma.

        -  Determine the number of days after stem cell transplantation to achieve absolute
           neutrophil count ≥ 500/mm^3 for 3 days and platelet count ≥ 20,000/mm^3 for 3 days
           (without transfusions) in patients treated with this regimen.

      Secondary

        -  Determine the response rate in patients treated with this regimen, based on lesions
           measurable by CT or MRI at study entry, patients with ^131I-MIBG scan-positive lesions
           only, and patients with minimal residual tumor in bone marrow who have complete response
           by immunocytology and morphology.

        -  Determine the tumor absorbed radiation dose in patients with measurable soft tissue
           lesions treated with this regimen.

        -  Correlate, if possible, TP53 mutations with response in patients with accessible bone
           marrow tumor treated with ^131I-MIBG.

      OUTLINE: This is a dose-escalation, multicenter study.

        -  Iodine I 131 metaiodobenzylguanidine (131I-MIBG) therapy: Patients receive^131I-MIBG IV
           over 2 hours on days 0 and 14.

      Cohorts of 3-6 patients receive escalating doses of ^131I-MIBG until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
      of 6 patients experience dose-limiting toxicity.

        -  Stem cell transplantation therapy: Patients undergo autologous peripheral blood stem
           cell transplantation on day 28. Patients receive filgrastim (G-CSF) IV over 1 hour OR
           subcutaneously daily beginning on day 28 and continuing until blood counts recover.

      Patients are followed every 3 months for 1 year and then annually thereafter.

      PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for this study within 2 years.
    

Intervention name(s): filgrastim; autologous bone marrow transplantation; peripheral blood stem cell transplantation; iobenguane I 131
Intervention type(s): Biological; Procedure; Procedure; Radiation
Intervention MeSH terms: 3-Iodobenzylguanidine
Primary purpose: Treatment
Keywords: recurrent neuroblastoma