• Age ≥ 12 years with weight ≥ 40Kg.

• ECOG performance status of ≤ 2.

• Newly diagnosed (frontline cohort), who are not eligible for high-intensity induction chemotherapy or relapsed/refractory (R/R cohort) AML or myeloid phenotype MPAL with either KMT2Ar, or NUP98r, or NPM1c.

• WBC must be below 25,000/ μL at time of enrollment. Patients may receive cytoreduction prior to enrollment.

• Baseline ejection fraction must be \> 40%.

• Adequate hepatic function (direct bilirubin \< 2x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible).

• Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease.

• Willing and able to provide informed consent.

• In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.

⁃ Women of childbearing potential must agree to adequate methods of contraception during the study and at least 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 and at least 3 months after the last treatment.