Long-term outcomes of responders in a randomized, controlled phase II trial of aptamer AS1411 in AML.

Abstract

6557 Background: AS1411 is the most advanced aptamer in oncology clinical development. It targets nucleolin, a protein upregulated on the surface of cancer cells. Data from a phase II study of AS1411 in relapsed and refractory AML were reported at ASCO 2009. In this update, we report follow-up data for the responders in the study. Methods: This randomized, multicenter phase II trial compared AS1411 plus high-dose cytarabine (HiDAC) to HiDAC alone as treatment for relapsed (≤3 previous lines of therapy) or refractory AML. Patients in cohort I were randomized 2:1 to receive AS1411 10 mg/kg/day IV CI days 1-7 + HiDAC 1.5 g/m2 bid days 4-7 (AS1411-10), or HiDAC alone for 4 days (control). Following safety assessment, a second cohort was randomized to receive AS1411 40 mg/kg/day + HiDAC (AS1411-40) or HiDAC alone. Objectives were comparison of response rates (CR+CRp), safety and tolerability between groups. For this analysis, we collected data on post-remission therapy (PRT) and overall survival (OS) among responders. Results: 71 patients were randomized: 22 to AS1411-10, 26 to AS1411-40 and 23 to control. 67 patients were evaluable for safety (AS1411-10, 21; AS1411 40, 25; control, 21). Grade 3 and 4 toxicities were similar across all groups: febrile neutropenia, neutropenia, thrombocytopenia, and infections. Deaths within 28 days of treatment were: AS1411-10, 1/21; AS1411-40, 2/25; and control, 3/21. 59 patients were evaluable for response; AS1411-10, 21% (4CR/19); AS1411-40, 19% (2CR+2CRp/21); and control, 5% (1CRp/19). PRT and OS data for responding patients are tabulated. Conclusions: This phase II trial suggested that addition of AS1411 to cytarabine may enhance anti-leukemic activity and that the combination has an acceptable safety profile in patients with relapsed and refractory AML. Follow-up suggests substantial survival durations in some patients responding to AS1411 + cytarabine. A phase IIb study is now evaluating responses, duration of responses and survival in AML patients randomized to AS1411 + cytarabine or cytarabine alone. Group CR/CRp PRT OS (months) Control CRp None 6 AS1411-10 CR Clinical trial 12 CR HiDAC 12+ CR HSCT 18+ CR HSCT 20+ AS1411-40 CRp Allo SCT 3 CR DLIs, Depocyt 5 CRp - 14+ CR - - Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisoma Antisoma Antisoma Antisoma