A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations

Inclusion Criteria:

* Confirmed primary AML relapsed or refractory after prior therapy, AML secondary to antecedent chemotherapy or radiation therapy, or AML due to prior myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) as defined by WHO criteria with presence of either FLT3 ITD and/or other FLT3 activating mutations
* Patients with secondary AML should have failed no more than two (2) prior regimens
* Patients with antecedent MDS/MPN, defined by WHO criteria, without any prior therapy for AML, regardless of the number of therapies for MDS/ MPN
* Patients with primary AML should have received no more than two (2) prior cytotoxic containing salvage regimens. Reinduction with the same regimen or stem cell transplant will not be considered a separate salvage regimen. Change of drugs will be considered a salvage regimen. Unlimited FLT3 TKI therapy (even in combination with cytotoxics/hypomethylating agents) is allowed for patients enrolled in cohort B
* Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within 30 day screening period
* Males and females age ≥18 years
* ECOG PS 0-2
* Adequate liver function, defined as bilirubin ≤1.5x ULN, ALT ≤3.0x ULN, and AST ≤3.0x ULN
* Adequate renal function, defined as serum creatinine ≤1.5x ULN
* Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia)
* Subjects should have received no anti-leukemic therapy (except hydroxyurea) prior to the first dose of crenolanib as follows: for 14 days for classical cytotoxic agents and for five times the t1/2 (half-life) for FLT3 inhibitors and antineoplastic agents that are neither cytotoxic nor FLT3 inhibitors (e.g. hypomethylating agent or MEK inhibitor)
* Negative pregnancy test for WOCBP
* Able and willing to provide written informed consent.

Exclusion Criteria:

* Absence of a FLT3 activating mutation
* \<5% blasts in blood or marrow at screening
* Concurrent chemotherapy, or targeted anti-cancer agents, other than hydroxyurea
* Patient with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
* HIV infection or active hepatitis B (defined as hepatitis B surface antigen positive) or C (defined as hepatitis C antibody positive)
* Known clinically active central nervous system (CNS) leukemia
* Patients less than 30 days post HSCT
* Subjects who have clinically significant graft versus host disease requiring treatment and /or have \>grade 2 persistent non hematological toxicity related to transplant
* Prior crenolanib treatment for a non-leukemic indication
* Major surgical procedures within 14 days of Day 1 administration of crenolanib.
* Unwillingness or inability to comply with protocol.