Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Inclusion Criteria: * Diagnosis of 1) AML (World Health Organization \[WHO\] classification definition of \>= 20% blasts) excluding acute promyelocytic leukemia (APL) or 2) MDS with \> 10% blasts (defined by the International Prognostic Scoring System \[IPSS\] classification). * For frontline Cohort: Patients aged \>= 60 years old who are not candidates for intensive induction therapy and agree to receive the proposed combination therapy will be enrolled. * Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on EITHER: * 75 years of age OR * \< 75 years of age with at least 1 of the following: * Poor performance status (Eastern Cooperative Oncology Group \[ECOG\]) score of 2-3. * Clinically significant heart or lung comorbidities, as reflected by at least 1 of: * Left ventricular ejection fraction (LVEF) =\< 50%. * Lung diffusing capacity for carbon monoxide (DLCO) =\< 65% of expected. * Forced expiratory volume in 1 second (FEV1) =\< 65% of expected. * Chronic stable angina or congestive heart failure controlled with medication. * Liver transaminases \> 3 x upper limit of normal (ULN). * Other contraindication(s) to anthracycline therapy (must be documented). * Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the principal investigator (PI). * Patients with newly diagnosed AML with poor …