A phase II study of elacytarabine plus idarubicin as second course remission-induction therapy in patients with acute myeloid leukemia.

Abstract

TPS207 Background: Elacytarabine is a fatty acid derivative (elaidic acid ester) of the antimetabolite cytarabine,which is widely used in the treatment of AML. Preclinical data has shown that the entry of cytarabine into tumour cells is dependent on the expression of specific membrane transporter proteins, particularly of hENT1 (human equilibrative nucleoside transporter 1). Decreased expression of hENT1 is a major factor in cytarabine resistance in childhood AML (Hubeek et al., 2005). For entry into cells elacytarabine is independent from transporters and offers therefore an opportunity for treating patients not likely to benefit from cytarabine. In phase I studies activity of elacytarabine has been observed in patients with refractory/relapsed AML, as monotherapy as well as in combination with idarubicin. Synergy has been observed for the combination elacytarabine and anthracycline in vitro, and in phase I the combination has demonstrated a safety profile similar to cytarabine and idarubicin. Methods: Patients with AML who have failed their first remission-induction course of a cytarabine based combination will be treated with elacytarabine in combination with idarubicin. The study is ongoing and will recruit up to 50 patients at 10 sites in the USA and Europe. As of 28th January, 8 sites are activated and 16 patients have been enrolled. The objective of the study is to determine response rates to the combination treatment and to evaluate by immunohistochemistry the hENT1 status of AML cells. The hENT1 expression level will be analysed at time of diagnosis and/or before elacytarabine treatment. The goal is to explore the relationship between response to cytarabine and to elacytarabine and the AML hENT1 status. Key Inclusion Criteria: Patients with AML who have received one previous cytarabine containing regimen and who have more than 5 % remaining blasts in the bone marrow following the first induction course. Bone marrow sample will be collected for the determination of the hENT1 expression level prior to treatment in the protocol. Patients must be 18 years of age or older and have an ECOG performance status of 0 – 2.