I-MIBG Escalating Dose Rapid Sequence Double Infusion Followed By Autologous Stem Cell Infusion For Refractory Neuroblastoma
- 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.
Primary Purpose: Treatment
Katherine K. Matthay, MD
University of California, San Francisco
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Children's Hospital Boston||Boston, Massachusetts 02115|