Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma

Ewing sarcoma (EWS) and osteosarcoma primarily affect adolescents and young adults. Common treatments include chemotherapy, surgery and radiation, however, there have been few recent advancements in the standard of care. By incorporating eflornithine (DFMO) as an additional therapy and/or maintenance therapy we hope to safely observe improved event-free survival and overall survival. There are 5 cohorts covered under this master protocol.

Cohort 1: Inclusion Criteria: 1. Participants must be ≤50 years of age at enrollment. 2. Histologically confirmed Ewing sarcoma that is refractory or in first or subsequent relapse. Histological confirmation either at initial diagnosis or disease progression. * Relapsed: Participants that have achieved CR at any point and then relapsed following/during standard of care therapy. * Refractory: Participants that failed to achieve CR after standard of care therapy or having progressed during standard of care therapy. * Note: Standard of care therapy for Ewing sarcoma includes multi-agent chemotherapy with local control consisting of either surgery and/or radiation therapy. 3. Extent of disease is judged by treating team to be amenable to the delivery of definitive local control (either definitive radiation, surgery, or a combination of these) at the time of study enrollment (to be completed after protocol defined Cycle 2). 4. Participants may enroll anytime during Cycle 1 or 2, prior to local control, as long as they received the same treatment during Cycle 1 and 2 as prescribed in this protocol. 5. Relapsed or refractory disease, including at least one of the following: * Tumor by CT or MRI * FDG-PET that is positive for disease * Bone Marrow biopsy/aspirate that is positive for disease Organ Function Requirements: 6. Participants must have adequate renal function as defined as: * For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr * For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr) * OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2 7. Adequate liver function defined as: 1. Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and 2. SGPT (ALT \