Phase III Randomized Study of Crenolanib versus Midostaurin Administered Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed Subjects with FLT3 Mutated Acute Myeloid Leukemia

A phase III randomized multi-center study designed to compare the efficacy of crenolanib with
that of midostaurin when administered following induction chemotherapy, consolidation
chemotherapy and bone marrow transplantation in newly diagnosed AML subjects with FLT3
mutation. About 510 subjects will be randomized in a 1:1 ratio to receive either crenolanib
in addition to standard first line treatment of AML (chemotherapy and if eligible,
transplantation) (arm A) or midostaurin and standard treatment (arm B). Potentially eligible
subjects will be registered and tested for the presence of FLT3 mutation. Once the FLT3
mutation status is confirmed and additional eligibility is established, subject will be
randomized and enter into the treatment phase.

Inclusion Criteria:

- Confirmed diagnosis of de novo AML according to World Health Organization (WHO) 2016
classification

- Presence of FLT3-ITD and/or D835 mutation(s) in bone marrow or peripheral blood

- Age ≥ 18 years and ≤ 60 years

- Adequate hepatic function within 48 hours prior to induction chemotherapy

- Adequate renal functions within 48 hours prior to induction chemotherapy

- ECOG performance status within 48 hours prior to induction chemotherapy ≤ 3

- Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy specified

Exclusion Criteria:

- Acute promyelocytic leukemia (APL)

- Known clinically active central nervous system (CNS) leukemia

- Severe liver disease

- Active infections

- Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)

- Known infection with human immunodeficiency virus (HIV)

- Prior systemic anti-cancer treatment (e.g. chemotherapy, tyrosine kinase inhibitors,
immunotherapy, or investigational agents)(except for hydroxyurea and/or leukapheresis)