A phase II study of AMN107, a novel inhibitor of Bcr-Abl, administered to imatinib-resistant or intolerant patients (pts) with chronic myelogenous leukemia (CML) in accelerated phase (AP).

6531 Background: AMN107 is a potent, highly selective, aminopyrimidine inhibitor which in vitro is 30-fold more potent than imatinib and is active against 32/33 imatinib resistant Bcr-Abl mutations.,This open-label study was designed to evaluate the safety and efficacy of AMN107 (400 mg bid) defined by hematologic/cytogenetic response (HR/CyR) rates in imatinib resistant or intolerant AP pts.,Preliminary data are presented for 22 pts (77% resistant and 23% intolerant to imatinib. Treatment is ongoing for 16 (73%) pts. Median age was 62 (43-76) yrs. Median duration of AMN107 exposure was 124 (3-207) days. Median time from AP diagnosis was 6 (0.2-56) mos. Three of 5 patients with data available had a Bcr-Abl mutation at baseline. HR occurred in 14 (64%) pts of which 10 (45%) were complete, 3 (14%) were marrow responses/no evidence of leukemia, and 1 return to chronic phase. CyR occurred in 6 pts (1 each complete, partial minor, and 3 minimal). All AE's occurring in ≥10% pts were thrombocytopenia (8 [36%] pts; Gr 3/4, 6 [27%] pts), fatigue (7 [32%]), anemia, (6 [27%]; Gr 3/4, 4 [18%] pts) pruritus, muscle spasms (6 [27%] pts each), bone pain, cough, (5 pts [23%] each) rash (5 [23%] pts; Gr 3/4, 1 [5%] pt), neutropenia (4 [18%] pts, all Gr 3/4), diarrhea, headache, myalgia, pyrexia (4 [18%] pts each), abdominal pain, chills, constipation, dyspnea, nausea, extremity pain, and peripheral edema (3 [14%] pts each). Two 2 deaths occurred, 1 pt with thrombocytopenia had a CNS bleed and 1 pt had disease progression.,These data suggest AMN107 is clinically active and has an acceptable safety profile when administered to pts with CML-AP. [Table: see text].