• Patients with AML who are newly diagnosed according to the WHO 2022 Classification and previously untreated except for hydroxyurea. ATRA pretreatment for suspected APL for less than 5 days is allowed. Eligible patients with AML arising from an antecedent hematologic disease (AHD) including MDS, may have been treated for their prior hematologic disease (except for allogenic transplant).

• Patients must be ≥ 18 and \< 75 years old.

• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.

• Presence of FLT3-ITD and/or TKD mutation(s) AND NPM1 mutation in bone marrow or peripheral blood

• Dose escalation phase only: Presence of any of the following adverse risk genetic characteristics:

‣ 2022 ELN adverse risk genetic features:

• t(6;9)(p23.3;q34.1)/DEK::NUP214

∙ t(v;11q23.3)/KMT2A-rearranged

∙ t(9;22)(q34.1;q11.2)/BCR::ABL1

∙ t(8;16)(p11.2;p13.3)/KAT6A::CREBBP

∙ inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1)

∙ t(3q26.2;v)/MECOM(EVI1)-rearranged

∙ -5 or del(5q); -7; -17/abn(17p)

∙ Complex karyotype, monosomal karyotype

∙ Mutations in either one of these genes: ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2

∙ Mutated TP53

⁃ NPM1 + FLT3-ITD + DNMT3A mutation

• LVEF ≥ 50% by MUGA or ECHO at screening.

• Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min; determined by the Cockcroft Gault formula.

• Adequate liver function as demonstrated by:

‣ aspartate aminotransferase (AST) ≤ 2.5 × ULN\*

⁃ alanine aminotransferase (ALT) ≤ 2.5× ULN\*

⁃ total bilirubin ≤ 1.5 × ULN\* \* Unless considered due to leukemic organ involvement. Note: Subjects with Gilbert's Syndrome may have a total bilirubin \> 1.5 × ULN per discussion with the Sponsor-Investigator

• Resolution of adverse reactions to prior drug therapy (such as hydroxyurea) to ≤ grade 1

• Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy based on the opinion of the treating physician.

• Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.

• Females of childbearing potential (i.e., not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum or urine pregnancy test performed within 7 days of day 1.

• Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)

• Consolidation should occur between 1-4 weeks following count recovery after induction and remission (must be confirmed by labs to document maximal response) is established. Subjects will receive medium intensity cytarabine -based consolidation in combination with midostaurin and revumenib if the following criteria are fulfilled.

‣ an induction response \< 5% blasts in the bone marrow and ANC \>1000 and PLT \>75000 for whom documented path report is submitted.

⁃ sufficiently fit (performance status \<3)

⁃ resolution of any adverse reactions to no greater than grade 1 severity