Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia.

Patients with imatinib-resistant or -intolerant accelerated phase CML (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase II trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. 119 patients were enrolled and had a median duration of treatment of 202 days (range 2-611). An HR was observed in 56 patients (47%, CI95% 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%, CI95% 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (CI95% 70%-87%). Non-hematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common >/= Grade 3 hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade >/= 3 bilirubin and lipase elevations occurred in 9% and 18% of patients respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228.