Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas

The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are: * Establish a recommended dose of AMXT 1501 in combination with DFMO * Test the safety and tolerability of AMXT 1501 in combination with DFMO * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

Inclusion Criteria: 1. Age: All participants : Must be a maximum of 26 years of age at diagnosis Age at enrollment by Phase: 1. Safety Run-in (Dose level 1)-The first three (3) participants enrolled will be ≥ 12 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the next three (3) participants enrolled who will be ≥6 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the Phase I. 2. Phase I and II: ≤ 26 years of age at diagnosis. 2. Pathology All participants must have a confirmed pathologic diagnosis of tumor type (except for DIPG): * Relapsed/refractory Neuroblastoma (NB) * Relapsed/refractory Embryonal tumor with multilayer rosettes (ETMR) * Relapsed/refractory Atypical teratoid rhabdoid tumor (ATRT) * Newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)- radiologic diagnosis acceptable * Relapsed/refractory Ewing Sarcoma (EWS) * Relapsed/refractory Osteosarcoma (OST) 3. Tumor assessment: Disease staging must be performed at baseline during the 28 day screening period prior to first dose of study drug. 4. Disease Status: Relapsed or Refractory Neuroblastoma Relapsed disease defined as: High-risk neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation, surgery, and immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol). Refractory disease defined as: High-risk neuroblastoma that 1) failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol, or 2) progression during upfront therapy or 3) with disease remaining after standard immunotherapy. Eligible NB participants may have active disease or no active disease. NB participants with no active disease need to meet the following criteria: Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy. NB participants with active disease need to meet the following criteria: * Received at least one recent treatment for their relapse/refractory disease and is stable (SD) or better on this treatment. * Participants must not have disease in any organs (including lungs, liver, or brain). Relapsed or refractory ETMR/ATRT Participants that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive/progressive to accepted curative therapy, including up-front chemotherapy and radiation and/or high-dose chemotherapy with stem cell rescue. ETMR/ATRT participants with no active disease need to meet the following criteria: Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy. ETMR/ATRT participants with active disease need to meet the following criteria: • Received at least one recent treatment for their relapse/refractory disease and is stable (SD) or better on this treatment. Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) Participants with DIPG to start greater than 30 days, and no longer than 60 days, after standard of care radiation therapy. Participants with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons on at least 1 axial T2-weighted image, are eligible. No histologic confirmation is required. Participants with metastatic disease are not eligible. Participants with a biopsy and no evidence of H3K27m mutations are eligible as long as they meet radiographic criteria. Participants with H3K27m altered DMG outside of the brainstem are not eligible. Participants with progression or recurrence after initial standard of care radiation are ineligible. Relapsed or refractory Ewing sarcoma and osteosarcoma Participants that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for Ewing sarcoma and osteosarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy. EWS/OST Participants with no active disease need to meet the following criteria: Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy. EWS/OST Participants with active disease need to meet the following criteria: • Received at least one recent treatment for their relapse/refractory disease and is stable (SD) or better on this treatment. 5. Participants must be able to swallow capsules. 6. Participants with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week and must not have progressive hydrocephalus at enrollment. 7. Participants 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. Small Molecule Inhibitor (anti-neoplastic agent): At least 7 days since the completion of therapy with a small molecule inhibitor. 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. 3. Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells except for anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.) which should be at least 2 weeks since prior treatment with a monoclonal antibody. 4. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site. Note: Participants with DIPG will be required to have had up front standard of care radiation. As above, participants with DIPG must be between 30-60 days post initial up- front radiation therapy. 5. Stem Cell Transplant: 1. Allogeneic: No evidence of active graft vs. host disease 2. Allo/Auto: ≥ 45 days must have elapsed since transplant. 6. MIBG Therapy: At least 6 weeks since treatment with MIBG therapy. 8. Participants must have a Lansky or Karnofsky Performance Scale score of \>/= 60 9. Participants must have adequate organ function at the time of enrollment: * Hematological: Hematological recovery as defined by ANC ≥750/μL (unsupported- \>24 hrs off G-CSF and 7 days off neulasta) * Liver: Adequate liver function as defined by AST and ALT \