Phase I trial of AP24534 in patients with refractory chronic myeloid leukemia (CML) and hematologic malignancies.

6511 Background: AP24534, an oral multiple tyrosine kinase inhibitor (TKI), is a potent pan-BCR-ABL inhibitor, including T315I. A phase I trial to assess its safety, maximum tolerated dose and activity is ongoing. Methods: Patients (pts) with refractory leukemia were enrolled on a dose escalation trial of daily AP24534. Dose levels were 2, 4, 8, 15, 30 and 60mg and a 45mg level is currently open. Results: As of 1/4/10, 48 pts, median age 62 yrs (range 26-85) have been enrolled. There are 42 CML pts (31 chronic [CP], 6 accelerated [AP], 5 blast phase [BP]) and 2 with Ph+ ALL. Prior therapies in CML pts include imatinib (I) (100% of pts), dasatinib (D) (88%), nilotinib (N) (65%); 97% and 81% of the Ph+ pts failed 2 and 3 prior TKIs, respectively and 88% had documented BCR-ABL mutations. Ph+ pts include 18 with T315I and 6 with F317L. 32 (67%) remain on therapy, median duration 61 days (range 5-360). Sixteen (33%) have discontinued; 7 (15%) for PD, 6 (13%) for investigator decision, 2 (4%) for unrelated deat...