Dissemination of medulloblastoma is an independent risk factor of poor prognosis. Dissemination of medulloblastoma at recurrence is nearly universally fatal. ABL1 and 2 have been recently found to mediate the dissemination of medulloblastoma. Genetically inactivating ABL1 and 2 resulted in decreased leptomeningeal medulloblastoma and improved overall survival (OS) in rodent models. ABL kinases have also been shown to play a role in the malignant properties of glioblastoma. Asciminib is an FDA approved for the treatment of chronic myeloid leukemia and is well tolerated, likely due to its specificity for ABL1 and ABL2. Asciminib is a P-glycoprotein (P-gp) substrate and thus may be susceptible to being pumped out of tumor cells and brain endothelial cells. It is unclear if asciminib can enter the central nervous system (CNS) and brain tumors in adequate concentration to have anti-tumor effects.

Inclusion Criteria:

• Ages 18-39 years old, inclusive.

• Radiographic evidence of a recurrent/progressive brain tumor.

• Tumor must be predominantly in an intraparenchymal location.

• Deemed operable (able to be resected or have an open or stereotactic needle biopsy) by treating neurosurgeon.

• ECOG Performance Status of ≥ 2. Patients who are unable to walk because of paralysis but who are up in a wheelchair will be considered ambulatory for the purposes of the performance score.

• Bone Marrow:

  • ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported).
  • Platelets ≥ 100,000/µl (may be supported by transfusion).
  • Hemoglobin > 8 g/dL (may be supported by transfusion).

• Renal:

  • Serum creatinine ≤ upper limit of institutional normal.

• Hepatic:

  • Bilirubin ≤ 1.5 times upper limit of normal for age.
  • ALT (SGPT) ≤ 3 times institutional upper limit of normal for age.
  • AST (SGOT) ≤ 3 times institutional upper limit of normal for age.

• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. All patients and/or their parents or legal guardians must sign an IRB approved written informed consent document.

Exclusion Criteria:

• Tumors suspected to be pituitary tumors or tumors of the meninges.
• Tumors that are suspected of a non-CNS primary location or history of non-CNS malignancy).
• Unable to take tablets orally
• Pregnant and/or breastfeeding. Subjects of childbearing potential must have a negative serum or urine pregnancy test within 10 days prior to Day 1.
• Active infection requiring treatment or an unexplained febrile (> 101.5o F) illness.
• Known immunosuppressive disease or human immunodeficiency virus infection.
• Any active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.
• Any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
• Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.