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7026 Background: CML-AP is often associated with imatinib-resistance and the occurrence of BCR-ABL mutations. This phase II open-label study was designed to evaluate the safety and efficacy of Nilotinib, a potent novel tyrosine kinase inhibitor, in imatinib-resistant or - intolerant CML-AP pts. Methods: Imatinib-resistance and -intolerance were defined using standard criteria, and all resistant pts failed imatinib >/= 600mg/day. Primary endpoint was a confirmed hematologic response (HR) determined by conventional ITT analysis. Nilotinib was started at 400mg BID and escalated to 600mg BID for inadequate responses. Results: Safety and efficacy are reported for first 64 consecutively enrolled pts completing >/= 8 mos treatment. 52 (81%) were imatinib-resistant; 12 (19%) -intolerant. Median duration of CML was 74 mos; median duration of prior imatinib use was 28 mos. Median duration of nilotinib exposure was 208 days; median average dose intensity (mg/days) was 787. Median cumulative duration of dose interruption was 23 days. Treatment is ongoing for 27 (42%) pts; 37 (58%) have discontinued (9 for AEs; 17 for disease progression). HR occurred in 38 (59%) pts, of which 15 (23%) were complete, 8 (13%) were marrow responses, and 15 (23%) returned to chronic phase. MCyR occurred in 23 (36%) pts; 14 (22%) were complete and 9 (14%) were partial. 6 (9%) pts did not respond; 5 (8%) pts had disease progression. Median time to HR was 1.0 (1–3) mos and to MCyR was 2.0 (1–8) mos. Estimated 1-yr survival rate was 69% and median duration of HR has not been reached. The most common Grade 3/4 AEs included neutropenia (45%), thrombocytopenia (40%), asymptomatic lipase elevations (17%), and anemia (16%) pts. No pts experienced Grade 3/4 peripheral edema, or pleural/pericardial effusions; 2 pts had pulmonary edema. Conclusion: In pts with CML-AP, nilotinib is an effective therapeutic option in CML-AP pts with imatinib-resistance or -intolerance and is generally well tolerated with acceptable rates of myelosuppression and minimal non- hematologic toxicities. No significant financial relationships to disclose.

6534 Background: AMN107 is a potent, highly selective, aminopyrimidine inhibitor which in vitro is 30-fold more potent than imatinib and active against 32/33 imatinib resistant Bcr-Abl mutations. Methods: 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 CP pts. Results: For this study which remains open to enrollment, preliminary data are reported for 67 pts including 39 (58%) with imatinib-resistant and 27 (40%) imatinib-intolerant CML (1 pt unknown). The median age was 62 (range 31–80) yrs and the median time from first diagnosis to treatment was 52 (range 5–279) mos. BCR-ABL mutations associated with imatinib resistance were detected in 11/17 (65%) pts at baseline. The median duration of AMN107 exposure was 129 (range 3–225) days. Treatment is ongoing for 50 (75%) pts with 17 (25%) pts discontinued (9 adverse events, 2 disease progression, 6 other). Major CyR was observed in 13 (19%) pts (6 complete, 7 partial), minor CyR was observed in 4 (17%) pts, and minimal CyR in 5 (7%) pts. Complete HR was reported in 35 of 42 (83%) pts without a baseline CHR. AE’s in ≥ 10% of pts were headache in 24 (36%) pts, fatigue in 21 (31%) pts (Gr 3/4 in 2 (3%)), pruritus in 19 (28.4%) pts (Gr 3/4 in 1 (2%)), rash in 18 (27%) pts (Gr 3/4 in 2 (3%)), nausea in 18 (27%) pts, diarrhea in 18 (27%) pts (Gr 3/4 in 1 (2%)), constipation in 11 (16%) pts, vomiting in 10 (15%) pts, thrombocytopenia in 10 (15%) pts (Gr 3/4 in 9 (13%)), anemia in 10 (14.9%) pts (Gr 3/4, 1 (2%)), neutropenia in 9 (13%) pts (Gr 3/4 in 8 (12%)), bone pain, muscle spasms, arthralgia, peripheral edema in 8 (12%) pts each, abdominal pain and myalgia in 7 (10%) pts each (Gr 3/4 in 1 (2%) each), and dyspnea in 7 (10%) pts. No deaths occurred. Conclusions: AMN107 has clinical activity and an acceptable safety and tolerability in pts with imatinib-resistant or intolerant CML-CP. [Table: see text]