• Ages 4 - 21 years

• Radiological diagnosis of Diffuse Midline Glioma with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami, and/or histological confirmation of H3K27M mutation of pontine or thalamic glioma. Subjects must have evidence of clinical and/or radiographic progression of disease.

• Lansky performance status score of at least 60 for subjects 16 years of age or younger.

• Karnofsky performance status of at least 60 for subjects greater than 16 years of age

• Organ Function:

‣ Adequate hematologic function defined as:

• Peripheral absolute neutrophil count ≥ 1,500/µL

∙ Platelet count ≥ 100,000/µL

∙ Partial thromboplastin time (PTT) and activated partial thromboplastin time (APTT): within normal institutional limits

⁃ Adequate renal function defined as:

• Potassium and magnesium levels within institutional limits

∙ Serum creatinine below the institutional upper limit of normal (ULN) for age and gender, or creatinine clearance: ≥ 60 mL/min/1.73m2

⁃ Adequate hepatic function defined as:

• Total bilirubin below the institutional ULN for age

∙ Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN

• Prior Therapy:

‣ Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.

⁃ Cytotoxic chemotherapy or anti-cancer agents known to be myelosuppressive: at least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy.

⁃ Anti-cancer agents not known to be myelosuppressive: at least 7 days must have elapsed from last dose of agent.

⁃ Antibodies: at least 21 days must have elapsed from infusion of last dose of antibody.

⁃ Interleukins, interferons, and cytokines: at least 21 days must have elapsed since the completion of interleukins, interferon, or cytokines.

⁃ Stem cell infusions: at least 42 days must have elapsed after completion of an autologous stem cell infusion, and at least 84 days must have elapsed after completion of an allogeneic stem cell infusion.

⁃ Cellular therapy: at least 42 days must have elapsed since the completion of any type of cellular therapy

⁃ Radiotherapy (XRT): at least 1 month must have elapsed after local XRT.

⁃ Subjects must be on a stable or decreasing dose of steroids, as well as stable dose of anti-seizure medication for at least 1 week.

• Subject able to give consent