Inclusion Criteria:

1. Patient must have one type of diagnosis below:

1. A glioma that is positive for the H3 K27M mutation (performed in a laboratory
with CLIA certification);

2. A grade III or IV glioma involving the thalamus, hypothalamus, brainstem,
cerebellum, midbrain, or spinal cord;

3. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine
epicenter and diffuse involvement of the pons. These patients are eligible with
or without a tissue biopsy.

2. Unequivocal evidence of progressive disease on as defined by RANO criteria or have
documented recurrent glioma on diagnostic biopsy.

3. Patient must have had previous therapy that includes radiotherapy.

4. Interval of at least 90 days from the completion of radiotherapy to the first dose
of ONC201. If patients are within 90 days of radiotherapy, they may still be
eligible if they meet one or more of the following criteria.

1. Progressive tumor is outside the original high-dose radiotherapy target volume
as determined by the treating investigator, or

2. Histologic confirmation of tumor through biopsy or resection, or

3. Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent
with true progressive disease, rather than pseudoprogression or radiation
necrosis obtained within 28 days of registration.

5. Patient must be at least 3 years of age.

6. Patient must weigh at least 10kg.

7. Patient must be able to swallow and retain orally administered medication. For
patients unable to swallow capsules, oral ONC201 will be administered as a liquid
formulation in Ora-Sweet.

8. From the projected start of scheduled study treatment, the following time periods
must have elapsed from prior anti-cancer treatments: 5 half-lives from any
investigational agent, 4 weeks from cytotoxic therapy (except 23 days for
temozolomide and 6 weeks from nitrosoureas), 6 weeks from anti-cancer antibodies
(except 21 days for bevacizumab), or 4 weeks (or 5 half-lives, whichever is shorter)
from other anti-tumor therapies.

9. Contrast-enhanced head CT or brain MRI within 21 days prior to start of study drug.

10. Adequate organ and marrow function as defined below:

1. Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior
to treatment (cycle 1 day 1, C1D1)

2. Hemoglobin >8.0 mg/dL without red blood cell transfusion ≤ 3 days prior to C1D1

3. Total serum bilirubin <1.5 X upper limit of normal (ULN)

4. AST (SGOT)/ALT (SGPT) ≤2 X ULN; ≤ 5 X ULN if there is liver involvement
secondary to tumor

5. Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2)

11. For patients post pubertal: Female patients must agree to use effective
contraception while taking ONC201 and for at least 90 days after completion of
treatment. Male patients must be surgically sterile or must agree to use effective
contraception while taking ONC201 and for at least 90 days after completion of
treatment. The decision of effective contraception will be based on the judgment of
the principal investigator.

12. Ability to understand a written informed consent document, and the willingness to
sign it. Assent will be obtained when appropriate based on the subjects age.

Exclusion Criteria:

1. Qualifies for participation in an ongoing ONC201 clinical trial or is already
participating in an ONC201 clinical trial.

2. Current or planned participation in a study of an investigational agent or using an
investigational device.

3. Evidence of diffuse leptomeningeal disease or CSF dissemination.

4. Any known systemic infection that, in the opinion of the investigator, could
compromise the safety of the patient, while taking ONC201.