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

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.

Inclusion

• Diagnosis of osteosarcoma

• High-risk disease, meeting 1 of the following criteria:

• Recurrent disease
• Refractory to conventional therapy
• Newly diagnosed metastatic disease with ≥ 4 pulmonary nodules or multiple bone lesions
• Unresectable primary tumor
• Prior intralesional resection allowed
• Measurable disease by technetium Tc 99m diphosphonate bone scan
• Refractory to all standard therapies or highly unlikely to respond to conventional treatment
• Performance status Karnofsky 60-100%
• Life expectancy more than 8 weeks
• Absolute neutrophil count > 500/mm^3
• Platelet count > 50,000/mm^3
• Creatinine clearance > 70 mL/min OR * Radioisotope glomerular filtration rate normal
• Recovered from prior chemotherapy

Exclusion

• Pregnant or nursing
• Positive pregnancy test for females of childbearing potential
• Fertile patients do not agree to use effective contraception
• Prior radiotherapy to the site of currently active disease
• Concurrent enrollment on protocol JHOC-J0094 allowed