Clinical activity of Crenolanib in patients with D835 mutant FLT3-positive relapsed/refractory acute myeloid leukemia (AML).

7027 Background: Development of D835 is a common mechanism of resistance to most FLT3 inhibitors. Crenolanib, a type I FLT3 tyrosine kinase inhibitor, has in vitro activity against FLT3 ITD and FLT3 D835. Crenolanib trials in relapsed/refractory FLT3 mutant AML (FLT3 ITD, FLT3 D835, FLT3 ITD/D835) are ongoing (NCT01522469, NCT01657682). Methods: Clinical data on the first 19 patients (7M, 12F) with a median age of 47 years (21-81) are currently available. 6 patients were refractory and 7 had relapsed within 6 months of induction therapy. 4 had undergone prior allogeneic transplants. 11/19 had progressed after exposure to ≥1 prior FLT3 TKI (8 Sorafenib, 7 AC220, 2 PLX3397, 1 PKC412,). 3 had received 2 or more prior FLT3 TKIs. Initially, crenolanib was given at a fixed dose of 100 mg PO TID but the dose was subsequently individualized to 200 mg/m2/d given in 3 divided doses. Results: Crenolanib had a Tmax of 1.5-2 hours and a T1/2 of 8-9 hours. Median day 15 trough levels (from 11 patients) ranged from 136 ...