Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

1. Documentation of Disease:

      - Unequivocal diagnosis of AML ( > 20% blasts in the bone marrow based on the WHO
      classification), excluding M3 (acute promyelocytic leukemia). Patients with
      neurologic symptoms suggestive of CNS leukemia are recommended to have a lumbar
      puncture. Patients whose CSF is positive for AML blasts are not eligible.

      - Documented FLT3 mutation (ITD or point mutation), determined by analysis in a
      protocol- designated FLT3 screening laboratory.

   2. Age Requirement:

      - Age ≥ 18 and < 60 years

   3. Prior Therapy:

      - No prior chemotherapy for leukemia or myelodysplasia with the following
      exceptions:

         - emergency leukapheresis

         - emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 5 days

         - cranial RT for CNS leukostasis (one dose only)

         - growth factor/cytokine support

      - AML patients with a history of antecedent myelodysplasia (MDS) remain eligible
      for treatment on this trial, but must not have had prior cytotoxic therapy (e.g.,
      azacitidine or decitabine)

      - Patients who have developed therapy related AML after prior RT or chemotherapy
      for another cancer or disorder are not eligible.

   4. Cardiac Function: Patients with symptomatic congestive heart failure are not eligible.

   5. Initial Laboratory Value: Total bilirubin < 2.5 x ULN (Upper Limit of Normal)

   6. Pregnancy and Nursing Status:

      - Non-pregnant and non-nursing due to the unknown teratogenic potential of
      midostaurin in humans, pregnant or nursing patients may not be enrolled.

      - Women of childbearing potential must have a negative serum or urine pregnancy
      test within a sensitivity of at least 50 mIU/mL within 16 days prior to
      registration.

      - Women of child-bearing potential must either commit to continued abstinence from
      heterosexual intercourse or commit to TWO acceptable methods of birth control:

         - one highly effective method (eg, IUD, hormonal (non-oral contraceptive),
         tubal ligation, or partner's vasectomy) and

         - one additional effective method (e.g., latex condom, diaphragm or cervical
         cap)

      - The two acceptable methods of birth control must be used AT THE SAME TIME, before
      beginning midostaurin/placebo therapy and continuing for 12 weeks after
      completion of all therapy.

      - Note that oral contraceptives are not considered a high effective method because
      of the possibility of a drug interaction with midostaurin.

      - Women of childbearing potential is defined as a sexually active mature woman who
      has not undergone a hysterectomy or who has not had menses at any time in the
      preceding 24 consecutive months.

      - Men must agree not to father a child and must use a latex condom during any
      sexual contact with women of childbearing potential while taking
      midostaurin/placebo and for 12 weeks after therapy is stopped, even if they have
      undergone a successful vasectomy.