Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients

For each arm:

The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.

Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.

Enrollment to be simultaneous to each arm.

Inclusion Criteria:

1. Confirmed diagnosis of refractory/relapsed AML or high-risk MDS

- Arm 1: Subjects must have received at least one prior therapy and a maximum of
three prior therapies

- Arm 2: Subjects must have received at least one prior therapy and a maximum of
three prior therapies. No prior treatment with 5-Azacitidine is allowed in this
arm.

2. FLT3 mutation positive (ITD, TKD or other)

3. ECOG PS 0-2

4. Adequate liver and renal function

5. Negative pregnancy test

6. Extramedullary leukemia allowed except CNS disease

Exclusion Criteria:

- Arm 1 and 2 Exclusion:

1. <5% blasts in marrow or blood at time of screening

2. Active HIV, hepatitis B or C

3. CNS leukemia

4. Clinically significant GVHD or organ dysfunction where chemotherapy specified by
protocol cannot be given

5. Patient with AML-M3 (APL)

6. Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C,
nonalcoholic steatohepatitis, sclerosing cholangitis)