This pilot clinical trial studies whole-body radiation therapy, systemic chemotherapy, and high-dose chemotherapy followed by stem cell rescue in treating patients with poor-risk Ewing sarcoma. Giving chemotherapy and radiation therapy before a peripheral blood stem cell or bone marrow transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is given to prepare the bone marrow for stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy
PRIMARY OBJECTIVES: I. To assess the safety and feasibility of whole-body magnetic resonance imaging (WB-MRI)-guided intensity modulated radiation therapy delivered concurrently with systemic chemotherapy to sites of metastatic disease in patients with relapsed, refractory and/or poor risk Ewing sarcoma. II. To assess the safety and feasibility of a novel consolidation regimen consisting of busulfan, melphalan and topotecan (topotecan hydrochloride) followed by autologous stem cell rescue, to be administered immediately after completion of radiation therapy in patients with relapsed, refractory and/or poor risk Ewing sarcoma. SECONDARY OBJECTIVES: I. To characterize the timing of myeloid and platelet engraftment. II. To estimate the overall and progression free survival probabilities. III. To estimate the cumulative incidence of relapse/progression and non-relapse related mortality. IV. To report the overall response rate (overall response rate \[ORR\]: complete response \[CR\]+partial response \[PR\]) and response duration. V. To descriptively compare the diagnostic imaging results (number and site of bone metastases) of whole-body MR imaging to those obtained by skeletal scintigraphy. OUTLINE: BLOCK I: Patients receive etoposide intravenously (IV) over 1-2 hours and ifosfamide IV over 1 hour on days 1-5. Patients also undergo WB-MRI-guided intensity-modulated radiation therapy twice daily (BID), 5 days a week, for approximately 4 weeks. Patients may also undergo 4 fractions of stereotactic radiation therapy (SRT) every other day (QOD), 3-8 fractions of stereotactic body radiation therapy (SBRT) QOD, or 10 fractions of 3-dimensional radiation therapy (3D RT) daily to sites of metastatic disease. BLOCK II: Patients receive high-dose chemotherapy comprising topotecan hydrochloride IV continuously over 24 hours on days -8 to -4, busulfan IV over 2 hours every 6 hours on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Patients undergo autologous peripheral blood or bone marrow stem cell infusion on day 0. After the stem cell infusion, patients are followed up for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given IV
Given IV
Undergo WB-MRI-guided IMRT
Given IV
Given IV
Given IV
Undergo autologous peripheral blood stem cell or bone marrow transplant
Undergo autologous peripheral blood stem cell transplant
Undergo autologous bone marrow transplant
City of Hope Medical Center
Duarte, California, United States
Percentage of patients who experience grade 4-5 non-hematologic toxicities assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Toxicities will be summarized as type, severity, date of onset, duration, reversibility, and attribution.
Time frame: Up to day 100 of Block II
Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST)
Objective tumor response for all patients will be summarized, including the number and percent responding.
Time frame: Up to 5 years
Progression-free survival (PFS)
PFS will be estimated using the Kaplan-Meier product-limit method; 95% confidence intervals (CIs) will be calculated using the logit transformation and the Greenwood variance estimate.
Time frame: Time from stem cell infusion to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years
Overall survival (OS)
OS will be estimated using the Kaplan-Meier product-limit method; 95% confidence intervals (CIs) will be calculated using the logit transformation and the Greenwood variance estimate.
Time frame: Time from stem cell infusion to death from any cause, assessed up to 5 years
Non-relapse mortality (NRM)
Cumulative relapse incidence will be estimated treating non-relapse related death events as competing risks and, conversely, NRM will be calculated controlling for relapse as a competing risk. Cumulative incidence of NRM and relapse-related mortality will be calculated using the method of Goole et al. Cumulative incidence differences will be assessed by Gray's test.
Time frame: Time from stem cell infusion to death event where the cause of death is not attributable to the underlying disease, assessed up to 5 years
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