REVEAL-1 Trial Data Show Voreloxin to be Safe and Effective in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

New Orleans, LA — Data from the fully enrolled REVEAL-1 trial presented at the 51st ASH Annual Meeting showed single-agent voreloxin, an investigational drug, to be a safe and effective treatment in elderly patients with treatment-naïve acute myeloid leukemia (AML). Voreloxin is a first-in-its-class anticancer quinolone derivative, a class of compounds that has not been previously used to treat cancer. Voreloxin intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest, and apoptosis.

REVEAL-1 is a phase 2 dose-optimization trial of single-agent voreloxin that included 113 elderly patients (median age, 74 y) with AML who were unlikely to benefit from standard induction chemotherapy. All patients had at least one adverse risk factor at enrollment, with the majority having unfavorable cytogenetics. The trial used three dosing schedules: schedule A, once weekly voreloxin for 3 weeks (n = 29); schedule B, once weekly voreloxin for 2 weeks (n = 35); and schedule C, voreloxin administered on days 1 and 4 at either 72 mg/m2 (n = 29) or 90 mg/m2 (n = 20).

Median survival was 8.7 months for those on schedule A, 5.8 months for those on schedule B, and 7.3 months for those receiving the 72 mg/m2 dose on schedule C. Patients on schedule A had a median duration of remission of 10.7 months and a 1-year survival of 38%. The median duration of remission was not reached for the other schedules, and it data were not ripe to determine 1-year survival.

Patients who were aged ≥75 years (n = 49) with at least one additional risk factor at diagnosis (identified by the National Comprehensive Cancer Network AML guidelines as having poor outcomes with standard treatment) experienced a complete response rate of 30% and a 30-day all-cause mortality of 5%. It was premature to evaluate survival data for this subset of patients. Patients on schedule C had response rates of 38%, with a 30-day all-cause mortality of 7% and a 60-day all-cause mortality of 17%. Patients on schedule C tolerated treatment better than patients on schedule A, leading the investigators to recommend the schedule C regimen as the pivotal dose regimen.

In a press statement, Robert K. Stuart, MD, professor of medicine, division of hematology/oncology, department of medicine, University of South Carolina, and an investigator on REVEAL-1, said, “Voreloxin has demonstrated a unique combination of anti-leukemic activity and tolerability, important for patients who are unlikely to benefit from standard induction therapy.” Dr Stuart went on to say, “Particularly encouraging are the durable response, tolerability, and promising survival results in the schedule C group. I look forward to seeing further data from this trial as it matures, particularly voreloxin’s durability and overall survival in schedule C.” ASH Abstract 1037.

Disclosures: All study investigators have affiliations with Sunesis.