MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma

Inclusion Criteria:

* Patients with newly diagnosed DIPG by magnetic resonance imaging (MRI); defined as patients with a pontine location and diffuse involvement of at least 2/3 of the pons are eligible without histologic diagnosis. For lesions with typical imaging features, biopsy is neither encouraged nor required for eligibility. Tumors that are biopsied will be eligible if proven to be supportive of the diagnosis of a DIPG. Consensus of diagnosis by the study team must be met.
* Patients who have completed focal radiotherapy within 14 weeks from time of enrollment are eligible.
* Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after, the date of completion of focal radiotherapy.
* Prior chemotherapy: Patients should be at least 30 days from last chemotherapy dose prior to start of CED infusion, with exception of antibody half-lives. For antibody therapies, at least 3 half-lives of the antibody after last dose of monoclonal antibody should have passed prior to CED infusion. Patients less than 30 days from last chemotherapy dose should be discussed with the study chair(s).
* Prior radiation: Patients must have received prior treatment with focal radiotherapy as part of initial treatment for DIPG and had their last dose at least 4 weeks prior to and no later than 14 weeks from the first CED treatment. Standard focal radiation therapy will include 54 to 60 Gy by external beam radiotherapy to the brainstem.
* Age ≥ 2 years of age to 21 years. Patients younger than 3 years of age may be enrolled on study at the discretion of the Study Chair(s) if supporting evidence that brainstem lesion represents a brainstem glioma.
* Karnofsky Performance Score ≥ 50 for patients \> 16 years of age and Lansky Performance Score ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are able to mobilize using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
* Life expectancy of greater than 12 weeks measured from the date of completion of radiotherapy.
* Corticosteroids: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
* Peripheral absolute neutrophil count (ANC) ≥ 1000/mm\^3.
* Hemoglobin ≥ 8g/dl.
* Platelet count ≥ 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
* Normal coagulation defined as normal International Normalized Ratio (INR) or per institutional guidelines.
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 milliliters (mL)/minute (min)/1.73 m\^2.
* A serum creatinine (mg/dL) based on age/gender as follows:

  * Age: 2 to \< 6 years; Male: 0.8; Female: 0.8
  * Age: 6 to \< 10 years; Male: 1; Female: 1
  * Age: 10 to \< 13 years; Male: 1.2; Female: 1.2
  * Age: 13 to \< 16 years; Male:1.5; Female: 1.4
  * Age ≥ 16 years; Male: 1.7; Female: 1.4
* Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.
* Serum glutamate pyruvate transaminase (SGPT) \[alanine aminotransferase (ALT)\] ≤ 110 U/L.
* Serum albumin ≥ 2 g/dL.
* Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.
* The effects of MTX110 on the developing human fetus are unknown. For this reason 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, for the duration of study participation and 4 months after completion of MTX110 injection administration. 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.
* Able to understand, and willing to sign, a written informed consent document.
* Patients who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Exclusion Criteria:

* Patients who had clinical and/or radiographic (MRI) progression of tumor following external beam radiation therapy.
* Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease.
* Patients with tumor morphology that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, or cysts that represent \> 50% of cross-sectional areas of the pons. These subjects should be discussed with the study chairs.
* Patients who are receiving any other investigational agents or other tumor-directed therapy.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to MTX110 or gadolinium.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 14 days of registration.
* Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the assessment of mass effect should be made by the study chairs and study neurosurgeons prior to any planned CED treatment.
* Untreated symptomatic hydrocephalus determined by treating physician.
* Patients with evidence of intra-tumoral hemorrhage \> 5 mm maximal diameter. These subjects should be discussed with the study chair.
* Subjects with prolonged corrected QT (QTc) (\> 450 msec) will be excluded from the study.