Gentuzumab Ozogamicin and Midostaurin Combination With Standard Cytarabine and Danunorubi Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia

Prior treatment

• Except for hydroxyurea, no other prior systemic anti-AML therapies may have been received prior to starting study therapy
• Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias
• Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
• Inability to take oral medication

Other illness

• Known history of veno-occlusive disease
• Known active human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection
• Patients with uncontrolled infection will not be enrolled until infection is treated
• Hypersensitivity to any study agent, or its excipients, when administered alone

Other

• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement to enter study)
• Acute promyelocytic leukemia (per World Health Organization classification)
• Active central nervous system (CNS) involvement by AML, as assessed at discretion of principal investigator (PI) or treating physician and confirmed by lumbar puncture
• Pregnancy or breastfeeding at the time of enrollment

• Ability to understand and the willingness to sign a written informed consent document
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Newly diagnosed AML as confirmed by bone marrow and/or peripheral blood examination as indicated, with:
  • Confirmed CD33 positivity, per institutional standards
  • Presence of FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation as confirmed by next-generation sequencing (NGS) or other molecular method
• Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN; local laboratory)
• Alanine aminotransferase (ALT) \< 2.5 x ULN
• Total bilirubin \< 2 x ULN (except for patients with known Gilbert's syndrome)
• Calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min OR serum creatinine \< 1.5 x the ULN
• Female patients of childbearing potential must agree to use adequate contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 4 months following the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 4 months following the last dose of study treatment