Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma
RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to tumor cells and not harm normal cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and samarium Sm 153 lexidronam pentasodium. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving samarium Sm 153 lexidronam pentasodium together with a peripheral stem cell transplant and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving samarium Sm 153 lexidronam pentasodium together with autologous stem cell transplant and radiation therapy works in treating patients with recurrent or refractory, metastatic, or unresectable osteosarcoma.
Procedure: peripheral blood stem cell transplantation
Radiation: Sm-EDTMP (low dose)
Radiation: sm-EDTMP (higher dose)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma|
- Tumor Response [ Time Frame: 1 week after study treatment ] [ Designated as safety issue: No ]WHO tumor measurement criteria used to determine response.
- Predictive Value of Imaging Studies [ Time Frame: At Time of Tumor Resection ] [ Designated as safety issue: No ]
- Overall and Progression-free Survival After Study Treatment [ Time Frame: Continual ] [ Designated as safety issue: No ]
- Toxicity at End of Study Treatment [ Time Frame: Continual and at End of Study ] [ Designated as safety issue: Yes ]
- Long Term Side Effects of Infusional Samarium-153 After Study Treatment [ Time Frame: Continual ] [ Designated as safety issue: Yes ]
- Correlative Dose of Radiation by Low Dose and High Dose Samarium-153 [ Time Frame: completion of treatment ] [ Designated as safety issue: No ]
|Study Start Date:||October 2004|
|Study Completion Date:||March 2009|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Cytoxan+Ifosfamide, Filgrastim pre samarium.'Sm-EDTMP (low dose). once counts recover, Sm-EDTMP (high dose) given. Peripheral blood stem cell transplantation is done 14 days later.
Filgrastim will be administered post post chemotherapy until target WBC count is achieved.
Other Name: NeupogenDrug: ifosfamide
Ifosfamide administered IV.
Other Name: IfexProcedure: peripheral blood stem cell transplantation
Peripheral blood stem cell transplantation is done 14 days after 2nd dose of Samarium is deliveredRadiation: Sm-EDTMP (low dose)
Sm-EDTMP (low dose) administered after autologous stem cell collectionRadiation: sm-EDTMP (higher dose)
Upon blood cell count recovery from Sm-EDTMP (low dose), Sm-EDTMP (higher dose) is administered followed in 14 days by peripheral blood stem cell transplantation.
- Determine the clinical response in patients with recurrent or refractory, metastatic, or unresectable osteosarcoma treated with high-dose samarium Sm 153 lexidronam pentasodium (^153Sm-EDTMP) and autologous peripheral blood stem cell transplantation followed by external-beam radiotherapy.
- Correlate the amount of radiation delivered to a tumor with low-dose ^153Sm-EDTMP with that of high-dose ^153Sm-EDTMP in patients treated with this regimen.
- Determine the overall and progression-free survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the long-term effects of this regimen in these patients.
- Determine the predictive value of fludeoxyglucose F 18 positron emission tomography (FDG-PET), diffusion-weighted MRI, and magnetic resonance spectroscopy for evaluation of treatment response in patients treated with this regimen.
OUTLINE: Patients are stratified according to resectability of the primary tumor (recurrent, refractory, or very high-risk disease vs unresectable primary tumor).
- Mobilization and collection of autologous peripheral blood stem cells (PBSCs)* : Patients receive ifosfamide IV daily for 5 days followed by filgrastim (G-CSF) subcutaneously daily. Patients then undergo leukapheresis for collection of autologous PBSCs until ≥ 2 x 10^6 CD34-positive cells/kg are collected.
NOTE: *Patients who have undergone PBSC collection before study entry proceed to high-dose samarium Sm 153 lexidronam pentasodium (153Sm-EDTMP) infusion without mobilization and collection of autologous PBSCs.
- 153Sm-EDTMP infusion: Patients receive a trace dose of ^153Sm-EDTMP** IV over 1-2 minutes and undergo bone scan 4, 24, and 48-72 hours later. Six weeks later, patients receive high-dose ^153Sm-EDTMP IV over 1-2 minutes and undergo repeat bone scans 4, 24, and 48-72 hours later.
NOTE: **Patients may receive the trace dose on protocol JHOC-J0094.
- Autologous peripheral blood stem cell transplantation (PBSCT): Between 12-14 days after administration of high-dose ^153Sm-EDTMP, patients undergo autologous PBSCT. Beginning 2 days later, patients receive G-CSF IV daily.
- External-beam radiotherapy: Patients then undergo external-beam radiotherapy to the sites of bulky disease.
- Surgery: Some patients may also undergo surgical resection of residual disease. After completion of study treatment, patients are followed periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00245011
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Principal Investigator:||David M. Loeb, MD, PhD||Sidney Kimmel Comprehensive Cancer Center|