Study of Enasidenib and Venetoclax in IDH2-Mutated Blood Cancers

Inclusion Criteria: * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance score of ≤2 * IDH2 (R140 or IDH R172) mutated AML disease status as determined by local laboratory * Relapsed and/or refractory acute myeloid leukemia (AML). Treatment-naïve patients who are not eligible for standard induction chemotherapy or high-risk myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) may also be eligible. * Adequate hepatic function * Adequate renal function * Willing and able to provide informed consent * In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic and non-cytotoxic (immunotherapy) agents Exclusion Criteria: * Known allergy or hypersensitivity to enasidenib or venetoclax * Previously received either an IDH2 inhibitor or BCL2 inhibitor * With any uncontrolled clinically significant medical conditions * The use of other chemotherapeutic agents or anti-leukemic agents, radiotherapy or other investigational therapy is not permitted during study with exceptions * Receiving concomitant treatment with strong cytochrome P450 2A (CYP3A4) inhibitors within 3 days of start of study therapy * Receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, St. John's Wort) within 3 days of start of study therapy. * Taking the following sensitive CYP substrate medications that have a narrow therapeutic range are excluded from the study unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment: paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2) * Active graft-versus-host-disease (GVHD) status post stem cell transplant * Severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications * Concurrent active malignancy under treatment * Administration or consumption of any of the following within 3 days prior to first dose of study drug: grapefruit or grapefruits products, Seville oranges (including marmalade containing Seville oranges) and start fruit * Heart-rate corrected QT (QTc) interval ≥480 msec (Fridericia's formula) except for underlying right-bundle branch block (RBBB). * Positive for HIV * Subject has an unacceptable white blood cell count * Positive urine pregnancy test, * Participants who not willing to maintain adequate contraception