N2000-01: Double Infusion of Iodine I 131 Metaiodobenzylguanidine Followed by Autologous Stem Cell Transplantation
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.
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: iobenguane I 131
|Study Design:||Primary Purpose: Treatment|
|Official Title:||I-MIBG Escalating Dose Rapid Sequence Double Infusion Followed By Autologous Stem Cell Infusion For Refractory Neuroblastoma|
|Study Start Date:||March 2004|
|Primary Completion Date:||February 2006 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00083135
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|UCSF Comprehensive Cancer Center|
|San Francisco, California, United States, 94143|
|United States, Indiana|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Wisconsin|
|University of Wisconsin Comprehensive Cancer Center|
|Madison, Wisconsin, United States, 53792-6164|
|Study Chair:||Katherine K. Matthay, MD||University of California, San Francisco|
|Principal Investigator:||Gregory Yanik, MD||University of Michigan Cancer Center|
|Principal Investigator:||John M. Maris, MD||Children's Hospital of Philadelphia|