ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas

This is a Phase II open-label study to investigate the safety and efficacy of ACT001 in patients with DIPG and H3K27-altered HGG.

Inclusion Criteria: 1. Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment. 2. Diagnosis: * Cohort A: Newly Diagnosed DIPG * Patients with newly-diagnosed DIPG with typical MRI findings (tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons) with or without biopsy and have completed radiation therapy (RT) within 28 to 35 calendar day prior to start of therapy. * Patients must have started RT \ 16 years of age and Lansky Performance Scale score \> 50% for patients ≤ 16 years of age (applies to all patients) Note: Patients who are unable to walk because of paralysis, but who are capable of using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 5. Prior anti-cancer therapy: * For Cohort A ONLY: * Surgery, radiation (focal to disease) and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy) are permissible. Temozolomide administered concurrently with RT is permissible. Bevacizumab use is permitted given the last dose was administered \>/= 21 days prior to enrollment. No other prior anticancer therapy for DIPG will be allowed. * Patients must enroll and start treatment on study between 28 and 35 calendar days post-completion of RT. * Patients must have started RT \ 21 days must have elapsed from the infusion of last dose of antibody 6. Radiation therapy: * All Cohort B patients: Patients must have received their last fraction of focal irradiation to new sites of progressive disease \> 14 days prior to enrollment. * Patients who received CSI must have received their last fraction \> 3 months prior to enrollment. * Progressive/recurrent disease: Patients who received re-irradiation to primary disease must have received their last fraction \> 3 months prior to study enrollment. * Refractory Disease: * Patients must have completed frontline RT \> 6 months prior to enrollment. * Patients who received re-irradiation to primary disease must have received their last fraction \> 3 months prior to study enrollment. 7. Stem Cell Transplant: Patients must be ≥ 3 months since autologous stem cell transplant. Patients who received allogenic stem cell transplant or solid organ transplant are not eligible for study 6. Organ Function Requirements (applies to all patients) 1. Adequate bone marrow function defined as: * Peripheral absolute neutrophil count (ANC) \> 1000/mm³ * Platelet count \> 100,000/mm³ (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) 2. Adequate renal function defined as: * Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m² or * A serum creatinine based on age/gender as follows (Schwartz et al. J. Peds, 106:522, 1985): Age Maximum Serum Creatinine (mg/dL) Male Female 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1.0 1.0 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 ≥ 16 years 1.7 1.4 3. Adequate liver function defined as: * total bilirubin must be \