Whole-body MRI-guided Intensity Modulated Radiation Therapy Combined With Systemic Chemotherapy Followed by High-Dose Chemotherapy With Busulfan, Melphalan and Topotecan and Stem Cell Rescue in Patients With Poor Risk Ewing's Sarcoma
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.
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 outcomes of patients treated on this protocol to a
comparable patient population treated with standard high-dose therapy [HDT] for high-risk,
advanced Ewing sarcoma.
VI. To descriptively compare the diagnostic imaging results (number and site of bone
metastases) of whole-body MR imaging to those obtained by skeletal scintigraphy.
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 every 6 hours on days -7 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Observed toxicities assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Toxicities will be summarized as type, severity, date of onset, duration, reversibility, and attribution.
Up to day 100 of Block II
City of Hope Medical Center
United States: Federal Government
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