6520 Background: Response to imatinib in accelerated phase (AP) and blast phase (BP) CML is inferior to chronic phase (CP). Relapse is frequent and associated with Bcr-Abl point mutations which interfere with imatinib binding. BMS-354825 is an orally available, dual SRC/ABL kinase inhibitor with 300-fold greater potency than imatinib. BMS-354825 has preclinical activity against 14 of 15 imatinib resistant Bcr-Abl mutants (Shah et al, Science, 2004). Methods: CA180002 is a phase I, dose-escalation study of BMS-354825 in patients with resistance or intolerance to imatinib. The study was initially restricted to CP CML but was amended to include AP and BP CML and Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients. Intrapatient dose escalation is permitted. Patient samples are analyzed for pharmacokinetics (PK), Bcr-Abl mutations, and CRKL, HCK, and LYN phosphorylation. Results: From May through November 2004, 8 AP, 18 BP CML and 3 Ph+ ALL patients were treated with 35 mg - 90 mg B...