BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas

This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma.

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of the combination of Poly (ADP-Ribose) polymerase (PARP) inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in adolescent and young adult (AYA) subjects with IDH1/2-mutant glioma, including the maximum tolerated dose (MTD) and characterization of dose-limiting toxicities (DLTs) in both, newly diagnosed and recurrent treatment arms.

With the completion of ABTC1801, a Phase I/II Study of BGB-290 with Temozolomide in Recurrent Gliomas with IDH1/2 Mutations, a maximum tolerated dose (MTD) for adults has been found. This study will advance to evaluate preliminary efficacy using this dose in patients 13-25 years of age.

EXPLORATORY OBJECTIVES:

I. Evaluate the preliminary efficacy of BGB-290 and temozolomide in terms of progression free survival (PFS) and overall survival (OS) in Arm A and B stratified by tumor diagnosis, calculated using the Kaplan-Meier method with a goal of improving the historical high grade glioma progression free survival of 10% and overall survival of 20% at 2 years.

II. Assess the mutational landscape studies via whole-exome sequencing (WES). III. Assessment of gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq).

IV. Assess the methylation profiling with Infinium methylation assays. V. Assess the oncometabolite profiling via liquid chromatography (LC)/mass spectrometry (MS)-MS.

VI. Assess the intratumoral drug level assessments via LC/MS-MS.

OUTLINE: Participants are assigned to 1 of 2 cohorts. The dose escalation component of the trial has been completed, which included patients ages 13-17 and the study will proceed with enrolling patients ages 13-25 years old onto the expansion cohort and target validation component at the ABTC pre-determined dose.

Arm A: Newly diagnosed IDH1/2-mutant high-grade glioma patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Arm B: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

COHORT B0: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor BGB-290 PO for 7 days pre-surgery at the ABTC-determined MTD. After recovery from surgery (14-28 days), the patient will proceed to the efficacy component of the trial.

After completion of study treatment, patients are followed up for 5 years.

Eligibility Criteria:
Inclusion Criteria:

* Arm A Only: Subjects must have histologically confirmed World Health Organization (WHO) grade III-IV newly diagnosed IDH1/2-mutant glioma.
* Arm B Only: WHO grades I-IV recurrent IDH1/2 mutant glioma. Subjects in Arm B must have magnetic resonance imaging (MRI) confirming progressive disease; re-biopsy is encouraged, but not required at the time of recurrence for confirmation.
* Patients with a primary spinal tumor, secondary glioma, or multifocal disease in the brain, but without evidence of diffuse leptomeningeal spread, are eligible. In cases where there are questions about multifocality versus diffuse leptomeningeal spread, the study chair or co-chair must be contacted to make a final decision on eligibility.
* Subjects must have IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins.
* Subjects must be willing to provide archival formalin-fixed embedded (FFPE) and frozen tissue specimens for biomarker studies if available.
* Subjects in Arm A must have been treated with maximal safe resection of primary tumor followed by adjuvant radiation therapy (RT). Treatment with TMZ during radiation is allowed but not required.
* Subjects in Arm B must have been treated with maximal safe resection of tumor.

  * Lower grade glioma (LGG) subjects who progressed after initial surgery alone are eligible. Any number of prior therapies are allowed.
  * High grade glioma (HGG) subjects enrolled on Arm B must have been treated with a minimum of maximal safe resection of primary tumor followed by adjuvant RT prior to recurrence. Any number of prior therapies are allowed.
* Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
* Myelosuppressive chemotherapy: subjects must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if nitrosourea.
* Biologic agent: subjects must have recovered from any toxicity related to biologic agents and received their last dose \>= 7 days prior to study registration.

  * For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
  * For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration.
* Monoclonal antibody treatment: at least three half-lives must have elapsed prior to registration, and subjects on bevacizumab must have received their last dose \>= 32 days prior to study registration.
* Subjects in Arm A should begin therapy with TMZ and BGB-290 after completion of radiation therapy and when all other eligibility criteria are met.
* For subjects in Arm B, patients must not have received radiation therapy within 4 weeks prior to the initiation of study treatment. Post-RT, the diagnosis of true progression versus ?pseudo-progression? can be challenging when imaging modalities are exclusively used, and thus an additional resection is encouraged if clinically indicated.
* Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3.
* Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
* Hemoglobin \>= 9 g/dL.
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance \>= 50 mL/min (calculated using the institutional standard method).
* Total serum bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN).
* Aspartate and alanine aminotransferase (AST and ALT) =\< 3 x ULN.
* Serum albumin \>= 2 g/dL.
* Subjects with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.
* Subjects who have neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
* Corticosteroids: Subjects who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
* The effects of BGB-290 on the developing human fetus are unknown. For this reason and because alkylating agents (such 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, for the duration of study participation and 4 months after completion of BGB-290 or TMZ 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.
* Subjects must be able to swallow capsules.
* Subjects must have the ability to undergo serial MRI scans (computerized tomography \[CT\] cannot substitute for MRI).
* A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
* Karnofsky \>= 50 for subjects \> 16 years of age and Lansky \>= 50 for subjects =\< 16 years of age. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

Exclusion Criteria:

* Subjects who are receiving any other investigational agents and/or subjects previously treated with small molecule inhibitors of mutant IDH1 or IDH2 proteins at any time may not be enrolled.
* Subjects who have received a PARP inhibitor previously.
* Subjects with active infection requiring antibiotics at time of therapy start.
* Subjects with other diagnosis of malignancy.
* Subjects with clinically significant active bleeding disorder, hemoptysis, or melena =\< 6 months prior to day 1.
* Subjects on therapeutic anti-coagulation with heparin, warfarin, or other anticoagulants:

  * Use of low-dose aspirin and/or non-steroidal anti-inflammatory agents are allowed.
  * Use of thrombolytic to establish patency of indwelling venous catheters is allowed.
  * Prophylactic anticoagulation for venous access devices is allowed as long as institutional normalized ratio (INR) is =\< 1.5 and partial thromboplastin time (aPTT) =\< 1.5 x institutional ULN.
  * Use of low-molecular weight heparin is allowed.
* Subjects with known disseminated leptomeningeal disease.
* Subjects with diffuse intrinsic pontine glioma (DIPG) are not eligible for this study.
* Unresolved acute effects of any prior therapy of grade \>= 2, except for adverse events (AEs) not constituting a safety risk by investigator judgement.
* Use =\< 10 days (or =\< 5 half-lives, whichever is shorter) prior to day 1 or anticipated need for food or drugs known to be strong or moderate Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TMZ or BGB-290.
* 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 subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose.
* Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with BGB-290 and TMZ. In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy.
* Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.