In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. TPS6637-TPS6637
Abstract:
TPS6637 Background: The promising phase 2 activity/tolerability profile of vosaroxin with cytarabine in first relapsed or refractory AML (N=69) with median overall survival (OS) 7.1 mo, combined CR 28% (CR 25%), median LFS 25 mo and 30-day all‑cause mortality 3%, supported phase 3 trial. VALOR (NCT01191801), a phase 3, randomized, controlled, double-blind trial, evaluates vosaroxin and cytarabine versus placebo and cytarabine in patients with first relapsed or refractory AML and incorporates an adaptive design. Primary objective is OS; secondary/tertiary objectives include CR rates, safety, EFS, LFS, and transplantation rate. Key eligibility criteria: persistent AML or first relapsed AML after 1 or 2 induction cycles that include at least 1 regimen of cytarabine with an anthracycline/anthracenedione; adequate cardiac, hepatic, renal function; and adults with no upper age restriction. Methods: VALOR is recruiting patients at over 100 sites in 14 countries in North America, Europe, and Australia/NZ. Enrollment opened Dec 2010; 183 patients enrolled through Dec 2011. Adaptive design: Base case assumed 40% improvement in median OS (hazard ratio, HR=0.71), 90% power, 2-sided alpha of 0.05. At the interim analysis (50% events), DSMB may recommend a 50% sample size increase from 450 to 675 evaluable patients if results indicate a larger sample size is required to reduce the risk of failing to confirm a clinically meaningful OS benefit (Mehta, Pocock, Stat Med 2010). In consideration of FDA and EMA guidance on Data Monitoring Committees and adaptive design with respect to trial integrity, operational bias, firewalls, and data confidentiality and archival, VALOR uses the Access Control Execution System (ACES ) to store, share, and archive confidential DSMB reports in a secure environment with an audit trail, and to facilitate communication between the DSMB and trial sponsor. The DSMB periodically reviews a combination of blinded and unblinded analyses while the study team remains blinded as specified in the DSMB charter. The DSMB recommended VALOR continue as planned after reviewing safety data in Dec 2011.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.tps6637
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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