Venetoclax in Combination With ASTX727 for the Treatment of Treatment-Naive High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Inclusion Criteria: * Patients with treatment-naive high-risk (HR)-MDS or CMML (intermediate \[Int\]-2 or high risk by the International Prognostic Scoring System \[IPSS\] with overall score \>= 1.5) with excess blasts \> 5. Note: Patients with therapy-related MDS are eligible. Hydroxyurea is allowed to lower the white cell count =\< 10,000/ul prior to initiation of venetoclax * Total bilirubin \< 3 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement * Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3.0 x ULN unless considered due to leukemic involvement * Creatinine \< 2 x ULN unless related to the disease * Signed written informed consent * Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment * Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment * Age \>= 18 years of age Exclusion Criteria: * Patients having received any prior BCL2 inhibitor therapy * Patients with MDS with IPSS risk categories low or Int-1 (overall IPSS score \< 1.5) * Patient with known human immunodeficie…