Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study
- Determine the maximum tolerated dose and toxic effects of iodine I 131
metaiodobenzylguanidine (131 I-MIBG) plus ablative doses of carboplatin and etoposide
administered with fixed-dose melphalan followed by autologous hematopoietic stem cell
transplantation in patients with refractory or residual high-risk neuroblastoma.
- Determine the number of days until blood counts recover in these patients after
receiving this treatment regimen.
- Determine the response rate to this treatment regimen in these patients.
- Determine the tumor dosimetry of 131 I-MIBG in patients with measurable soft tissue
OUTLINE: This is a dose-escalation study of iodine I 131 metaiodobenzylguanidine (131
I-MIBG), carboplatin, and etoposide. Patients are stratified according to glomerular
filtration rate (at least 100 mL/min vs 60-99 mL/min).
Patients undergo peripheral blood stem cell harvest or bone marrow harvest at least 2 weeks
prior to treatment with 131 I-MIBG.
Patients receive 131 I-MIBG IV over 120 minutes on day -21; melphalan IV on days -7 to -5;
carboplatin and etoposide IV continuously over 96 hours on days -7 to -4; autologous
hematopoietic stem cell transplantation IV over 15-30 minutes on day 0; and filgrastim
(G-CSF) subcutaneously or IV starting on day 0 and continuing until blood counts recover.
Radiotherapy is administered to the primary tumor site and metastatic sites twice daily for
7 consecutive days within 6 weeks of transplantation or once blood counts have recovered.
Cohorts of 3-6 patients receive escalating doses of 131 I-MIBG, carboplatin, and etoposide
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at day 84, and then 2 months later if there is a complete response
and/or partial response. Patients who continue therapy on other protocols are followed
before starting the new therapy. All patients are followed for life for any delayed toxic
effects related to study therapy, secondary malignancies, disease status, and survival.
PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per stratum) will be accrued for this
study within 2-3 years.
Primary Purpose: Treatment
Katherine K. Matthay, MD
Children's Hospital Los Angeles
United States: Food and Drug Administration
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|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|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Texas Children's Cancer Center||Houston, Texas 77030-2399|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Lucile Packard Children's Hospital at Stanford University Medical Center||Palo Alto, California 95798|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus||Atlanta, Georgia 30322|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|
|Children's Hospital Boston||Boston, Massachusetts 02115|