Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

Inclusion Criteria: * All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma. * All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy. * Specific Criteria by Arm: Arms 1 and 2: Subjects with no active disease: i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease). o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required. ii. No evidence of disease metastatic to bone marrow. Arm 3 \[CLOSED TO ENROLLMENT\]: Measurable or evaluable disease, including at least one of the following: Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site. * Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy. * Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines: 1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea). 2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor. 3. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair. 4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells. 5. Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody. 6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site. 7. Stem Cell Transplant: 1. Allogeneic: No evidence of active graft vs. host disease 2. Allo/Auto: ≥ 2 months must have elapsed since transplant. 8. MIBG Therapy: At least 8 weeks since treatment with MIBG therapy * Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher. * Life expectancy \> 2 months * All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below. * Subjects must have adequate organ functions at the time of registration: * Hematological: Total absolute neutrophil count ANC ≥750/μL * Liver: Subjects must have adequate liver function as defined by AST and ALT \<5x upper limit of normal (Normal=45), Bilirubin \<1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen. * Renal: 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. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr * Subjects of childbearing potential must have a negative pregnancy test. Subjects of childbearing potential must agree to use an effective birth control method. Subjects who are lactating must agree to stop breast-feeding. * Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative). Exclusion Criteria: * BSA of \<0.25 m2. * Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible. * Subjects that received a dose of DFMO in combination with etoposide are not eligible. * Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation. * Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy. * Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator. * Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.