A phase II study of nilotinib administered to imatinib resistant or intolerant patients with chronic myelogenous leukemia (CML) in blast crisis (BC) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL)

Abstract

7040 Background: Nilotinib is a highly selective Bcr-Abl tyrosine kinase inhibitor that is 30-fold more potent than imatinib. In a phase I trial, nilotinib demonstrated efficacy and favorable tolerability in these pts. These results expand upon the phase I experience Methods: This phase II open-label study was designed to evaluate the safety and efficacy of nilotinib in adult imatinib-resistant or - intolerant BC pts or pts with relapsed/refractory Ph+ALL. Primary endpoint was investigator assessment of best hematologic response for BC and complete response for Ph+ALL pts. Nilotinib was started at 400mg BID with escalation to 600mg BID if no adequate response. Results: Safety and efficacy data are reported for 120 BC (27 lymphoid, 87 myeloid, 6 unknown) and 41 Ph+ALL pts (37 active disease, 4 residual disease, 38 relapsed, 3 refractory). 60% of pts had >35% Ph+ metaphases for BC and 31% for Ph+ALL. Median ages was 54 yrs for BC and 46 yrs for Ph+ALL pts. Chromosomal abnormalities other than Ph+ were noted in 64 (53%) BC and 12 (29%) Ph+ALL pts. Extramedullary involvement was present in 44 (37%) BC and 3 (7%) Ph+ALL pts. Treatment is ongoing for 21 (18%) BC and 4 (10%) Ph+ALL pts. Majority of discontinuations were due to disease progression [61 (51%) in BC; 26 (63%) in Ph+ALL). Median treatment duration was 53 (1–441) and 72 (3–363) days for BC and Ph+ALL, respectively. Median dose intensity was 800mg/day for both pt groups. CHR was reported in 25 (21%) pts, marrow responses in 7 (6%) pts, and return to chronic phase in 10 (8%) pts. Complete response was reported in 10 (24%) Ph+ALL; of which, 1 patient had minimal residual disease. The most common Grade 3/4 AEs were thrombocytopenia (41%), neutropenia (28%), pneumonia (11%), and anemia (27%) in BC and thrombocytopenia (24%) in Ph+ALL pts. During study period death occurred in 9 (8%) BC and 3 (7%) Ph+ALL pts. No Ph+ALL pt developed CNS disease while on therapy. Conclusions: Nilotinib has significant clinical activity and is well tolerated in imatinib-resistant or -intolerant BC and relapsed/refractory Ph+ALL pts. Nilotinib represents an important new treatment option for these pts in which there remains a high unmet medical need. No significant financial relationships to disclose.