Inclusion Criteria:

          -  Patients must have histopathologic or molecular confirmation of either IDH-mutant DA
             or IDH-mutant AA. Acceptable IDH mutations for study eligibility include any IDH1
             mutation at codon 132 or any IDH2 mutation at codon 172.

          -  Age >= 16 years. The intended neurocognitive tests have not been validated in children
             below the age of 16.

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%).

          -  Hemoglobin > 9.0 g/dL

          -  Leukocytes >= 3.0 x 10^9/L

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN)

          -  Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) =<
             1.5 x ULN

          -  Patients on a stable dose of anti-coagulation therapy will be allowed to participate
             if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are
             compatible with an acceptable risk-benefit ratio as per the investigator's discretion.

          -  Total bilirubin =< 1.5 x institutional ULN and < 3 mg/dL for patients with Gilbert's
             disease

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) &
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
             institutional ULN

          -  Creatinine =< 1.5 x institutional ULN or creatinine clearance >= 60 mL/minute

          -  If there is history of human immunodeficiency virus (HIV) infection, patients must be
             on effective antiretroviral therapy and HIV viral load must be undetectable within 6
             months of study enrollment.

          -  If there is history of chronic hepatitis B virus (HBV) infection, patients must have
             either been treated or are on suppressive therapy (as indicated), and HBV viral load
             must be undetectable.

          -  If there is history of hepatitis C virus (HCV) infection, patients must have been
             treated and HCV viral load must be undetectable.

          -  Patient must have measurable disease by RANO criteria (dose expansion cohort only).

          -  Patient must be at least 7 days beyond stereotactic biopsy and/or at least 14 days
             beyond open craniotomy at the time of registration.

          -  Patients must have been on a stable or decreasing dose of corticosteroids over the
             last 7 days at the time of registration.

          -  Patients must have been on a stable or decreasing dose of antiepileptic therapy over
             the last 14 days at the time of registration.

          -  Females of childbearing potential must have a negative pregnancy test (=< 14 days)
             prior to start of trial treatment. The effects of CB-839 HCl on the developing human
             fetus are unknown. For this reason and because alkylating agents as well as TMZ are
             known to be teratogenic, 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. 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 4 months after completion of CB-839 HCl
             (telaglenastat) administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial.

          -  Patients with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
             function using the New York Heart Association functional classification. To be
             eligible for this trial, patients should be class 2B or better.

          -  Availability of archival FFPE tumor tissue collected within 12 months prior to
             registration.

        Exclusion Criteria:

          -  Patients must not have received prior chemotherapy to treat the glioma.

          -  Patients who are receiving any other investigational agents.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to CB-839 HCl (telaglenastat) or TMZ.

          -  Patient must not have received prior radiation therapy to the brain. Prior radiation
             therapy to the head and neck is also excluded if radiation fields overlap.

          -  No prior use of Gliadel wafers.

          -  Patient must have no evidence of either infratentorial or spinal involvement with
             tumor.

          -  Patients who are unable to swallow tablets.

          -  Patients who are at risk for impaired absorption of oral medication including, but not
             limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal
             resection.

          -  Patients with uncontrolled intercurrent illness.

          -  Patients with a "currently active" second malignancy other than non-melanoma skin
             cancers. Patients are not considered to have a "currently active" malignancy if they
             have completed therapy and are free of disease for more than 3 years.

          -  Pregnant women are excluded from this study because CB-839 HCl (telaglenastat) is an
             agent with the potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for AEs in nursing infants secondary to treatment of the
             mother with CB-839 HCl (telaglenastat), breastfeeding should be discontinued if the
             mother is treated with CB-839 HCl (telaglenastat). These potential risks may also
             apply to TMZ.

          -  Adolescent patients who require sedation for magnetic resonance imaging (MRI) or
             magnetic resonance spectroscopy (MRS).

          -  Patients with psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  The primary language of communication for the patient must be English (dose expansion
             cohort only). The intended neurocognitive tests have not been validated in patients
             who do not primarily speak English.