Testing a New Chemotherapy Drug, KRT-232 (AMG-232) in Combination With Decitabine and Venetoclax in Patients With Acute Myeloid Leukemia

Inclusion Criteria: * Relapsed/refractory AML (\>= 5% blasts in bone marrow or extramedullary leukemia); adverse cytogenetics, e.g., as defined by the Medical Research Council (MRC) Prognostic Groupings; secondary AML; organ dysfunction arising from significant co-morbidities not directly linked to leukemia; Eastern Cooperative Oncology Group \[ECOG\] = 2) or not willing to undergo intensive chemotherapy * Patients must have measurable disease as defined the presence of \>= 20% blasts in bone marrow or extramedullary leukemia * Eligible patient must show evidence of wild-type (WT) p53 as assessed by DNA sequencing; note, that since patients with AML have a rapidly proliferating disease, patient can be enrolled and begin treatment prior to obtaining the results of this test; patients who are found to the TP53 mutated will be removed from study and can continue on single agent decitabine; however patients will continue to be followed for toxicity * Age \>= 18 years; because no dosing or adverse event data are currently available on the use of KRT-232 (AMG-232) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials * ECOG performance status =\< 2 (Karnofsky \>= 60%) * White blood count =\< 25 x 10\^9/L * Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (\< 2.0 x ULN for subjects with documented Gilbert's syndrome or \< 3.0 x ULN for subjects for whom the indirect bilirubin level suggests an extra…