A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant accelerated and blast phase chronic myeloid leukemia (CML): Results from CA180002

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