A Phase II study of VNP40101M in elderly patients (pts) with de novo poor risk acute myelogenous leukemia (AML)

Abstract

7026 Background: VNP40101M is a novel alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links and has previously shown anti-leukemic activity in clinical trials. Methods: A confirmatory Phase II study of single agent VNP40101M was conducted in elderly pts with poor risk de novo AML. Pts received induction therapy with 600 mg/m2 VNP40101M as a single 60-minute infusion on day 1. A 2nd induction cycle could be administered to pts with a PR or hematologic improvement. Pts with CR or CRp were able to receive consolidation with araC 400mg/m2/day CIV for 5 days. Pts were eligible if they were ≥ 60 yrs and had 1 poor risk factor: age ≥ 70, ECOG PS= 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Pts with a prior diagnosis of MDS or favorable cytogenetics were excluded. Results: Enrollment was completed August 14, 2007. 85 pts were treated: median age (range): 73 (61–87); male: 59%. The majority of pts (89%) had 2 or more risk factors. The most common risk factors were age ≥ 70 (76%), pulmonary dysfunction (58%), cardiac dysfunction (48%) and unfavorable cytogenetics (48%). The response rate was 35% overall (23 CR + 7 CRp); 27% in pts with unfavorable cytogenetics, 34% in pts age ≥ 70 and 37% in pts with PS= 2. 27 responders (90%) achieved remission after 1 induction cycle. 18 responders (60%) received araC consolidation per protocol. 32 VNP40101M-related serious adverse events (SAEs) have been reported in 28 of 85 pts. The most common SAEs were related to myelosuppression or infection. Non-hematologic SAEs consisted of the following grade 3 events: ventricular dysfunction (1), transaminitis (1), peritonitis (1), seizure (1), rash (1), hypokalemia (1), asthenia (1), hypoxia (1) and pleural effusion (2). 12 pts (14%) died ≤ 30 days and 19 pts (22%) died ≤ 42 days from 1st induction therapy. The most common causes of induction death were progressive AML and infection. Health resource utilization data will be presented. Conclusions: This Phase II single-agent study of VNP40101M confirms anti-leukemic activity in elderly pts with de novo AML despite additional poor risk factors such as unfavorable cytogenetics. Severe and/or serious drug-related non-hematological toxicity is uncommon. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Vion Pharmaceuticals, Inc Vion Pharmaceuticals, Inc Vion Pharmaceuticals, Inc