Pre-Registration Inclusion Criteria:

- United States (US) and Canadian sites:

* This review is mandatory prior to registration to confirm eligibility; patients must
be willing to submit tissue samples for mandatory central pathology review submission;
it should be initiated as soon after surgery as possible

- Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation
prior to submission for central path review

- Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility,
the 1p/19q analysis results will be accepted from the local site, as determined
by either a locally available or reference laboratory (for US, must be Clinical
Laboratory Improvement Act [CLIA] certified); acceptable methods for
determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by
genomic sequencing or methylomic analyses; US and Canadian sites must send a copy
of the official report to the pathology coordinator and quality assurance
specialist (QAS)

- Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic
analyses; this should be performed at the local site (US: performed in a CLIA
certified laboratory); the site must send a copy of the official report to the
pathology coordinator and QAS

Registration Inclusion Criteria:

- Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if
they have had a prior surgical procedure > 3 months earlier for low grade glioma, as
long as the patient has not received prior radiation or prior chemotherapy

- Histological evidence of World Health Organization (WHO) grade III anaplastic glioma
or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the
presence of an either IDH1 or IDH2, both as established by a local or referenced
laboratory qualified for the study

* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or
oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q

- Patients with codeleted low grade gliomas must also be considered "high risk" by
exhibiting one or more of the following characteristics:

- Age >= 40 and any surgical therapy

- Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than
gross total resection)

- Documented growth following prior surgery (NOTE: patients with prior surgery
cannot have received prior radiation, chemotherapy or targeted therapy)

- Intractable seizures

- Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks
prior to registration; patient must have recovered adequately from the effects of
surgery

- Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to
registration

- Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration

- Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days
prior to registration

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3
x ULN obtained =< 21 days prior to registration

- Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration

- Negative serum or urine pregnancy test done =< 7 days prior to registration, for women
of childbearing potential only

- Willingness and ability to personally complete neurocognitive testing (without
assistance) and willingness to complete the QOL testing, (either personally or with
assistance)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2

- Written informed consent

- Willingness to return to enrolling institution for follow-up during the active
monitoring phase (that is, the active treatment and observation portion) of the
study); patients who have been formally transferred to another active and approved
site participating in this study would not need to return to the enrolling institution
for this purpose

- Willingness to allow the provision of tissue samples for correlative research, as long
as adequate tissues are available; patients will not be excluded from participation in
the study, if they are willing to allow provision of tissues for the correlative
research, but there are insufficient quantities of tissue for the correlative analyses
(e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to
allow the provision of blood samples for correlative research; patients are not
excluded from participation in the study, if they are willing to provide the mandatory
biospecimens for translational/correlative research, but for logistical reasons the
specimens(s) were not obtainable or if the volume collected was insufficient

Registration Exclusion Criteria:

- The following categories are ineligible:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception or contraceptive method during this study and 6 months following
the completion of chemotherapy treatments

- History of prior radiation therapy or chemotherapy for glioma; note: patients who have
a history of prior low grade glioma (with or without a distant history of prior
surgery for that glioma), but who have never received prior chemotherapy or radiation
therapy for the glioma are eligible for the study

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Concomitant serious immunocompromised status (other than that related to concomitant
steroids) that would compromise the safety of the patient on the study

- Patients known to be human immunodeficiency virus (HIV) positive and currently
receiving retroviral therapy are not eligible; note: patients known to be HIV
positive, but without clinical evidence of an immunocompromised state, are eligible
for the study

- 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

- Receiving any other investigational agent that would be considered as a treatment for
the primary neoplasm

- Other active malignancy within 5 years of registration; exceptions: non-melanotic skin
cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior
malignancy, the patient is not eligible if they are receiving other specific treatment
(with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if
they have received prior total body irradiation which included the brain

- History of myocardial infarction =< 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

- Recent history of hepatitis infection or if the treating physician determined that the
patient would be at significant risk of reactivation of hepatitis

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/7/22. Questions regarding updates should be directed to the study team contact.