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Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma

Phase 2
Completed
Conditions
Sarcoma
Interventions
Biological: filgrastim
Procedure: peripheral blood stem cell transplantation
Radiation: Sm-EDTMP (low dose)
Radiation: sm-EDTMP (higher dose)
Registration Number
NCT00245011
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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 (cluster of differentiation 34)-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 (Johns Hopkins Oncology Center)-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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Samarium-153sm-EDTMP (higher dose)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.
Samarium-153filgrastimCytoxan+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.
Samarium-153peripheral blood stem cell transplantationCytoxan+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.
Samarium-153Sm-EDTMP (low dose)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.
Samarium-153ifosfamideCytoxan+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.
Primary Outcome Measures
NameTimeMethod
Tumor Response1 week after study treatment

WHO (World Health Organization) tumor measurement criteria used to determine response.

Secondary Outcome Measures
NameTimeMethod
Correlative Dose of Radiation by Low Dose and High Dose Samarium-153completion of treatment
Long Term Side Effects of Infusional Samarium-153 After Study TreatmentContinual
Toxicity at End of Study TreatmentContinual and at End of Study
Overall and Progression-free Survival After Study Treatmentup to 4 years
Predictive Value of Imaging StudiesAt Time of Tumor Resection

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

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