Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib

To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.

Inclusion Criteria: 1. Age \> 18 years 2. Participants must have a documented IDH1 gene mutation 3. Participants with a diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML), high-risk MDS by IPSS-R or IPSS-M; OR 4. Participants with newly diagnosed AML not eligible or appropriate for intensive chemotherapy are also eligible. (Phase 2 portion only) 5. To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities: 1. Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina). 2. Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second \[FEV1\] ≤65%). 3. Creatinine clearance ≥30 mL/min to \1.5 to .3.0 x upper limit of normal (ULN) 5. ECOG performance status of 2 or 3 6. Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy 6. Eastern Cooperative Oncology Group (ECOG) Performance Status \ 25 x 10\^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.) 8. Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. A) Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).