Expanding Nilotinib Access in Clinical Trials (ENACT), an open-label multicenter study of oral nilotinib in adult patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase or blast crisis.

Nilotinib has shown favorable safety in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic (CML-CP) or accelerated phase (CML-AP) who failed prior imatinib, and superior efficacy over imatinib in newly diagnosed Ph+ patients with CML-CP. Reported here are the efficacy and safety data for patients in CML-AP (n = 181) or blast crisis (CML-BC) (n = 190; myeloid BC, 133; lymphoid BC, 50; unknown, seven) enrolled in an expanded access phase IIIb study. Non-hematologic adverse events were mostly mild to moderate. Drug-related myelosuppression was generally manageable with dose reductions or interruptions and infrequently led to discontinuation of nilotinib. Drug-related grade 3/4 elevations in serum bilirubin and lipase were infrequent. While an analysis of efficacy was not the primary objective of this study, significant hematologic and cytogenetic responses were observed. These results support the safety and efficacy of nilotinib in patients with advanced CML in AP and BC.