N2001-02: I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more tumor cells are killed. Giving radiation therapy after an autologous peripheral stem cell or bone marrow transplant may kill any remaining tumor cells.
PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine together with combination chemotherapy and radiation therapy works in treating patients who are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or refractory neuroblastoma.
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: iobenguane I 131
Radiation: radiation therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma|
- Response (complete response, very good partial response, and partial response) at 60-days post stem cell infusion [ Designated as safety issue: No ]
- Event-free survival [ Designated as safety issue: No ]
- Time to progression [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
- Determine the response rate in patients with relapsed or refractory neuroblastoma treated with iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and combination chemotherapy comprising carboplatin, etoposide, and melphalan followed by autologous bone marrow or peripheral blood stem cell transplantation and radiotherapy.
- Determine the hematopoietic and nonhematopoietic toxicity of this regimen in these patients.
- Determine the tumor self-absorbed radiation dose (TSARD) in patients with measurable soft tissue lesions treated with this regimen.
- Correlate the TSARD with tumor response in patients with measurable residual soft tissue disease treated with this regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to risk (poor-risk group [mixed or no response to induction therapy or progression during or after induction therapy] vs good-risk group [partial response after 4 courses of induction therapy]) and kidney function at study entry (glomerular filtration rate [GFR] ≥ 100 mL/min vs GFR 60-99 mL/min)
- Stem cell harvest: Patients undergo a peripheral blood stem cell harvest or bone marrow harvest provided they have an adequate number of cells available. At least 2 weeks later, patients proceed to iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and combination chemotherapy.
- 131I-MIBG and combination chemotherapy: Patients receive ^131I-MIBG IV over 2 hours on day -21, carboplatin IV continuously on days -7 to -4, etoposide IV continuously on days -7 to -4, and melphalan IV over 1 hour on days -7 to -5.
- Stem cell infusion and filgrastim (G-CSF): Three days after completion of chemotherapy, patients undergo transplantation of either stem cells or bone marrow on day 0. Patients also receive G-CSF subcutaneously or IV over 1 hour once daily beginning on day 0 and continuing until blood counts return to normal.
- Radiotherapy: Once blood counts return to normal, patients undergo radiotherapy to primary and metastatic sites that have not received previous irradiation over 12 days beginning after day 42.
After completion of study treatment, patients are followed for 2 years and then periodically thereafter.
PROJECTED ACCRUAL: Approximately 50 patients (40 low-risk patients and 8-10 high-risk patients) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00253435
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucile Packard Children's Hospital at Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94143|
|United States, Georgia|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comer Children's Hospital|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|C.S. Mott Children's Hospital at University of Michigan Medical Center|
|Ann Arbor, Michigan, United States, 48109-0286|
|United States, New York|
|Morgan Stanley Children's Hospital of New York-Presbyterian|
|New York, New York, United States, 10032|
|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, 19104-4318|
|United States, Texas|
|Cook Children's Medical Center - Fort Worth|
|Fort Worth, Texas, United States, 76104|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital|
|Houston, Texas, United States, 77030-2399|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|United States, Wisconsin|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Madison, Wisconsin, United States, 53792-6164|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Study Chair:||Gregory Yanik, MD||University of Michigan Cancer Center|
|Principal Investigator:||Katherine K. Matthay, MD||University of California, San Francisco|
|Principal Investigator:||John M. Maris, MD||Children's Hospital of Philadelphia|