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.