Glioma Clinical Trials

• Age ≥ 36 months

• Newly diagnosed pathologically proven diffuse midline glioma (DMG) (H3 K27M mutant) or radiographic and/or pathologically proven pontine DMG (tumors with an epicenter in the pontine and diffuse involvement in at least 50% of the axial diameter of the pons)

• Patient must have received standard of care radiation ≥ 4 but ≤ 8 weeks prior to study enrollment Note: The eligibility determination, enrollment, pre-surgical planning, and M032 administration must be completed within 8 weeks of radiation therapy completion.

• The tumor characteristics for enrollment are as follows:

• The lesion must be ≥ 1.0 cm and ≤ 4.0 cm in diameter and surgically accessible as determined by MRI

• For patients diagnosed with supratentorial DMG, tumors larger than 4.0 cm may be eligible if they can be surgically debulked to ≤ 4.0 cm

• Patients must have fully recovered from acute treatment-related toxicities prior to entering this study. The study entry timepoint is defined as the time of consent

• Previous treatment guidelines (if applicable):

• Monoclonal antibody (i.e., bevacizumab): patient must have received last dose ≥ 21 days prior

• Radiation: Patients must have received their last fraction of radiation ≥ 4 weeks and ≤ 8 weeks prior to study entry

• Temozolomide: Patients must have received their last dose of chemotherapy ≥ 4 weeks prior

⁃ Normal hematological, renal, and liver function as defined below:

• Hemoglobin \> 9g/dL

• White blood cell ≥ 3,000/μL

• Absolute neutrophil count ≥ 1000/mm3

• Platelets ≥ 100,000/mm3

• PT or PTT ≤ 1.3 x control

• Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m2 (cystatin C preferred) for patients with creatinine levels above institutional normal

• Total Bilirubin ≤ 1.5 mg/dl

• Transaminases \< 3 times above the upper limits of the institutional norm

• Patients \< 16 years, Modified Lansky score ≥ 60; patients ≥ 16 years, Karnofsky score ≥ 60

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

• Postmenopausal (no menses in greater than or equal to 12 consecutive months).

• History of hysterectomy or bilateral salpingo-oophorectomy.

• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

• History of bilateral tubal ligation or another surgical sterilization procedure.

• Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study agent administration.

• Written informed consent in accordance with institutional and FDA guidelines must be obtained from the patient or legal guardian