glutaminase inhibitor cb-839 and azacitidine in treating patients with advanced myelodysplastic syndrome

Conditions: Acute Myeloid Leukemia With Multilineage Dysplasia; Blasts 20-30 Percent of Bone Marrow Nucleated Cells; Blasts 20-30 Percent of Peripheral Blood White Cells; Chronic Myelomonocytic Leukemia; High Risk Myelodysplastic Syndrome; IPSS Risk Category Intermediate-2; Myelodysplastic Syndrome

Summary: this phase i/ii trial studies the side effects of glutaminase inhibitor cb-839 in combination with azacitidine in treating patients with myelodysplastic syndrome that has spread to other places in the body. glutaminase inhibitor cb-839 and azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

primary objectives: i. to determine the safety, tolerability and clinical activity of glutaminase inhibitor cb-839 (cb-839) in combination with azacitidine (aza) for patients with advanced myelodysplastic syndrome (mds). secondary objectives: i. to explore the pharmacokinetics (pk) of cb-839 in combination with aza. ii. to explore the pharmacodynamics (pdn) of cb-839 in combination with aza. iii. to assess overall survival, event-free survival and duration of response of cb-839 in combination with aza. outline: patients receive glutaminase inhibitor cb-839 orally (po) twice daily (bid) on days 1-28 and azacitidine subcutaneously (sc) or intravenously (iv) over 10-40 minutes on days 1-7. after completion of study treatment, patients are followed up at 28 days.

Eligibility criteria:
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