Safety Assessment of Two Schedules of Intravenous Infusions of SNS-595 for the Treatment of Hematologic Malignancies

This study primarily determined the safety and tolerability of escalating doses of vosaroxin (SNS-595) in 2 dose schedules, and assessed the PK profile of vosaroxin and defined a recommended dose regimen for Phase 2 studies. Secondarily the study assessed potential biomarkers and antileukemic activity.

Patients assigned to 1 of 2 schedules (A and B) in cohorts of at least 3 patients received vosaroxin (SNS-595) intravenously (IV) for up to 4 cycles: once weekly (Days 1, 8, 15 in Schedule A) or twice weekly (Days 1, 4, 8, 11 in Schedule B). Dose escalation proceeded independently for Schedule A (18 mg/m2 initially) and Schedule B (9 mg/m2 initially) in the absence of Dose-limiting Toxicity (DLT) based on a modified Fibonacci sequence. The incidence of DLT during Cycle 1 determined the maximum-tolerated dose (MTD) allowing for treatment delays of up to 14 days to resolve clinically significant abnormal laboratory values or related treatment-emergent adverse events (TEAEs) and one dose reduction of 25% in case of above. Patients with stable disease, hematologic improvement, or partial remission with stable blast counts or experiencing clinical benefit in the opinion of the investigator were eligible to receive vosaroxin for up to 4 additional cycles.