• Patients at least 18 years of age will be considered for inclusion without bias against gender identity, race, or ethnicity

• Ability to comprehend the investigational nature of the study and provide written informed consent

• Patients with previously untreated, morphologically documented AML based on World Health Organization (WHO) 2008 definitions who are ineligible for standard of care (SOC) intensive chemotherapy induction and also meet the following criteria:

‣ Documented intermediate- or adverse-risk AML based on European Leukemia Network (ELN) 2022 criteria

⁃ Note: Cases of AML/myelodysplastic syndrome (MDS) overlap with 10-19% bone marrow (BM) or peripheral blood (PB) blasts will be considered

⁃ Note: Cases of acute promyelocytic leukemia (PML) and AML with BCR::ABL1 fusions will be excluded

• Eastern Cooperative Oncology Group (ECOG) performance ≤ 2 (Patients aged ≥ 75 years, at the time of consent)

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Patients aged ≥ 75 years, at the time of consent)

‣ High total bilirubin values may require indirect and direct bilirubin testing. Individuals with known Gilbert's syndrome may be considered for enrollment despite high indirect (and total) bilirubin

• Creatinine clearance (CrCl) of ≥ 60 mL/min (estimated using the Cockcroft Gault formula or measured by 24 hours urine collection. If altered, CrCl is determined to be related to concomitant medication that alters renal function

• Patients aged ≥ 18 to 74 years (ECOG performance status \[PS\] ≤ 3 is accepted) at consent must meet ≥ 1 of the following criteria defining a co morbidity:

‣ ECOG PS of 2 or 3 (Note: Patients ≥ 18 to 74 years of age with PS of 0-1 must meet criteria of one of the following comorbidities.)

⁃ Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina

⁃ Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%

⁃ CrCl ≥ 30 mL/min to \< 45 ml/min

⁃ Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × ULN;

∙ High total bilirubin values may require indirect and direct bilirubin testing. Individuals with known Gilbert's syndrome may be considered for enrollment despite high indirect (and total) bilirubin

⁃ Other comorbidities that the physician judges to be incompatible with intensive chemotherapy (IC). In these cases, the comorbidity must be reviewed and approved by the principal investigator (PI) before study enrollment

• Ability to swallow oral medications

• No ongoing anticoagulation or antiplatelet therapy within 14 days of start of treatment with IADA

• No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention

• No history of stroke or intracranial hemorrhage within 180 days of start of IADA

• No major bleeding event, as defined by the International Society of Thrombosis and Hemostasis (ISTH), within 12 weeks of start of IADA

• Uncorrected international normalized ratio (INR) or activated partial thromboplastin time (aPTT) of \< 1.5 x ULN.

‣ If INR or aPTT \> 1.5 x ULN has been corrected (prior to enrollment), then history of disseminated intravascular coagulation (DIC) must be absent

• White blood cell (WBC) \< 20 x 10\^9/L prior to study start. Cytoreduction prior to study treatment is allowed with

‣ Hydroxyurea for up to 14 days and until 24 hours prior to start of IADA; or

⁃ Leukapheresis for up to 14 days prior to start of IADA

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.0 x institutional ULN

‣ Lower hepatic function may be considered if liver enzyme abnormalities are determined by the treating MD and principal investigator (PI) to be due to leukemic infiltration

• Willing and able to

‣ Adhere to study schedule of activities and life style restrictions while on treatment;

⁃ Provide bone marrow (BM) aspirate and core biopsy samples; and

⁃ Accept supportive and prophylactic care for hematologic toxicities, infection, and immediate sequelae, including transfusions

• Negative pregnancy test within 72 hours of start of IADA for persons of childbearing potential (PCBP)

• Willingness to comply with study requirements for contraception, as follows: PCBP and sperm-producing participants who are sexually active with a PCBP must use study approved contraception from start of investigational product (first dose of IADA) until 6 months after the last dose of IADA. Pregnancy is exclusionary because the agents used in this study have the potential for teratogenic or abortifacient effects