Multicenter open label study of subcutaneous (SC) omacetaxine (OMA) in imatinib (IM)-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation.

7021 Background: Omacetaxine mepesuccinate (semi-synthetic homoharringtonine, HHT) is clinically active against Ph+ CML, with a mechanism of action independent of tyrosine kinase (TK) inhibition. Currently available TK inhibitors have not demonstrated activity in CML patients with the T315I mutation. We are evaluating the safety/efficacy of SC OMA in Pts with IM-resistant T315I+ Ph+ CML.,Eligible Pts- adult T315I+ CML following imatinib failure or intolerance. Induction schedule: 1.25 mg/m SC twice daily (BID) for 14 days every 28 days until complete hematologic response (CHR) or hematologic improvement. Maintenance schedule: 1.25 mg/m BID for 7 days every 28 days, for up to 24 mos.,To date, 29 Pts have been enrolled, 17 in chronic phase (CP), 6 in accelerated phase (AP) and 6 in myeloid blast phase (BP). Median age: 58 yrs (19-83), median disease duration: 58 mo. (9-287). Overall hematologic response rate: CP 64%, AP 100%, and BP 34%, with 45% CHR in CP patients. Overall cytogenetic response rate (CyR): CP 27% and AP 25%, with 2 complete CyR in CP and 1 minor CyR in AP. Median time to response 2 mo. (1-5), median duration of response 4 mo. (1-13+). Incidence of grade 3/4 events: thrombocytopenia 52%, anemia 43%, neutropenia 43%, febrile neutropenia 22% and diarrhea 17%. Grade 1-2 local injection site pain or erythema in 23% and 13% of cases, respectively. T315I transcript levels are no longer detectable in 50% (7/14) of Pts.,OMA therapy in T315I+ IM-resistant CML Pts has been well tolerated and resulted in durable CHRs and cytogenetic responses. [Table: see text].