A double blind placebo-controlled randomized phase III study of high dose continuous infusion cytosine arabinoside (araC) with or without VNP40101M in patients (pts) with first relapse of acute myeloid leukemia (AML)

7051 Background: VNP40101M (101M) is a novel alkylating agent that has demonstrated anti- leukemia activity both as a single agent and in combination with araC (Giles et al, 2004, 2005, 2007). Methods: Eligible pts were ≥ 18 years old, PS 0–2, and in relapse after first CR (CR1) of 3–24 months. Pts were randomized using a 2:1 schema to araC 1.5 g/m2 (d1–3) + 101M 600 mg/m2 (treatment group [T]), or araC 1.5 g/m2 (d1–3) + placebo (control group [C]). Pts with bone marrow improvement could receive a 2nd induction (ind). Pts with CR/CRp were consolidated according to original assignment (101M dose 400 mg/m2). Primary endpoint was CR/CRp (ORR). Secondary endpoints were response duration, progression-free and overall survival (OS). The design included 420 pts, with an interim analysis by data safety monitoring board (DSMB) for safety and efficacy of the first 210 patients. Results: Following DSMB review in May 2007 the study was placed on hold due to a disproportionate death rate between T & C. T (140 pts) and...