Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome

Inclusion Criteria:

* Signed, informed consent must be obtained prior to any study specific procedures
* Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts (RAEB)-T (acute myeloid leukemia \[AML\] with 20-30% blasts and multilineage dysplasia by French-American-British \[FAB\] criteria) by World Health Organization (WHO) and chronic myelomonocytic leukemia (CMML) are eligible
* Subjects with high-risk MDS (i.e. International Prognostic Scoring System \[IPSS\] Intermediate-2 or high-risk; or R-IPSS high or very-high risk). Patients with Intermediate-1 risk by IPSS or Intermediate risk by R-IPSS and with IDH1 or IDH2, or high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
* Subjects with prior hypomethylating agent therapy exposure may be eligible based on discussion with the principal investigator (PI)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Serum bilirubin =\< 2 x the upper limit of normal (ULN) (except for patients with Gilbert's disease)
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =\< 3 x the laboratory ULN
* Creatinine clearance \> 30 mL/min based on the Cockcroft-Gault equation
* Able to understand and voluntarily sign a written informed consent, and willing and able to comply with protocol requirements
* Resolution of all treatment-related, non-hematological toxicities, except alopecia, from any previous cancer therapy to \< grade 1 prior to the first dose of study treatment
* Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (\>= 45 years old and without menses for \>= 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential

Exclusion Criteria:

* Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
* Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
* Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
* Clinically significant gastrointestinal conditions or disorders that may interfere with study drug absorption, including prior gastrectomy
* Patients with known active central nervous system (CNS) disease, including leptomeningeal involvement
* Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last 6 months
* Subjects with a corrected QT (QTc) \> 480 ms (QTc \> 510 msec for subjects with a bundle branch block at baseline)
* Nursing or pregnant women
* Subjects with known hypersensitivity to study drugs or their excipients