A Phase II Study of Nilotinib, a Novel Tyrosine Kinase Inhibitor Administered to Imatinib Resistant or Intolerant Patients with Chronic Myelogenous Leukemia (CML) in Blast Crisis (BC) or Relapsed/Refractory Ph+ Acute Lymphoblastic Leukemia (ALL).

Nilotinib is a highly selective, aminopyrimidine which is 30-fold more potent in vitro than imatinib and active against 32/33 imatinib resistant Bcr-Abl mutations. This open-label study was designed to evaluate the safety and efficacy of Nilotinib administered at a dose of 400 mg bid by hematologic/cytogenetic response (HR/CyR) rates in imatinib resistant or intolerant BC patients or patients with relapsed/refractory Ph+ALL. Preliminary data are presented for 96 BC and 34 Ph+ALL patients. The median age for the Ph+ALL patients was 47 years (range 26 to 75) and for the BC patients 54 years (range 19 to 78). There were 16 males and 18 females with Ph+ALL and 60 males and 36 females with BC. Chromosomal abnormalities other than Ph+ were noted in 12 (35%) and 48 (50%) of BC patients. Extramedullary involvement was present in 3 (9%) Ph+ALL patients and 35 (37%) of BC patients. Treatment is ongoing for 8 (24%) of Ph+ALL patients and 31 (32%) of BC patients. The majority of discontinuations were due to disease progression and occurred in 18 (53%) BC patients and 41 (43%) Ph+ALL. CHR was reported in 12 (13%) BC patients, marrow responses in 6 (6%), return to chronic phase and stable disease in 17 (18%) patients each. Complete responses were reported in 2 (6%) Ph+ALL 1 relapsed/refractory and 1 patient with minimal residual disease). The most frequent Grade 3 or 4 adverse events occurring in patients with Ph+ALL were thrombocytopenia in 3 (9%) patients, and 2 (6%) patients each had neutropenia, blood bilirubin increased, ALT elevation and bone pain. The most frequent Grade 3 or 4 adverse events occurring in patients with BC were thrombocytopenia 23 (24%), neutropenia 17 (18%), and anemia in 9 (9%) of patients. Nilotinib has clinical activity and an acceptable safety and tolerability profile in pts with imatinib resistant or intolerant BC and relapsed/refractory Ph+ ALL patients.