A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML

Inclusion Criteria:

* Diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL (acute promyelocytic leukemia) with PML-RARA are not eligible
* Documented presence of an ITD and/or TKD activating mutation in the FLT3 gene, as determined by analysis in a Novartis designated laboratory An exception will be patients who are enrolled into the part 1 in Japan, who may be treated with midostaurin irrespective of AML FLT3 genotype.
* Patients must meet the following laboratory value criteria that indicate adequate organ function at the screening visit:

  * Estimated creatinine clearance ≥ 30 ml/min
  * Total bilirubin ≤ 1.5 x ULN, except in the setting of isolated Gilbert syndrome
  * Aspartate transaminase (AST) ≤ 3.0 x ULN
  * Alanine transaminase (ALT) ≤ 3.0 x ULN
* Suitability for intensive chemotherapy in the judgment of the investigator

Exclusion Criteria:

* Neurologic symptoms suggestive of CNS leukemia unless CNS leukemia has been excluded by a lumbar puncture. Patients with CSF fluid positive for AML blasts are not eligible
* Developed therapy-related AML after prior radiotherapy (RT) or chemotherapy for another cancer or disorder
* Known hypersensitivity to midostaurin, cytarabine or daunorubicin or to any of the excipients of midostaurin/placebo, cytarabine or daunorubicin
* Abnormal chest X-ray unless the abnormality represents a non-active, or non-clinically significant finding, such as scarring (subjects with controlled non active lung infection are eligible)
* Known impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin
* Cardiac or cardiac repolarization abnormality
* Pregnant or nursing (lactating) women
* Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 4 months after stopping medication