Venetoclax and ASTX727 for the Treatment of Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia

Inclusion Criteria: * Patients with AML by the World Health Organization (WHO) classification who have failed prior therapy, refractory to it or relapsed after prior response. Patients with isolated extramedullary AML are eligible (cohort 1) * Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * For cohort 2 (frontline elderly or unfit AML AML), the following inclusion criteria: * Confirmed newly diagnosed AML * Ineligible for induction therapy defined as * Either age \>= 75 years * Or 18-74 years of age with at least one comorbidity (chronic heart failure \[CHF\] requiring therapy or eject fraction \[EF\] =\< 50%, carbon monoxide diffusing capability \[DLCO\] =\< 65% or forced expiratory volume in 1 second \[FEV1\] =\< 65%, or ECOG 2 or 3) * Creatinine clearance ≥30 mL/min to \<45 mL/min * Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0 × upper limit of normal (ULN) * Creatinine clearance ≥ 45 ml/min unless related to the disease (e.g. infiltration) * Total bilirubin \< 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement * Alanine aminotransferase (ALT) \< 3 x ULN unless considered due to leukemic involvement (by biopsy or imaging) * Able to give written informed consent * Oral hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and hydroxyurea while the patient is on active study treatment through cycle…