Conditions: Myelodysplastic Syndrome
Keywords: INT-2 or high-risk MDS
Allocation:  | Intervention model: SEQUENTIAL
Enrollment: 10
Healthy volunteers: no

Brief summary:
Study WCMC IST/VOS/MDS evaluates the safety and tolerability of escalating doses of vosaroxin in adult patients with pathologically confirmed Myelodysplastic Syndrome, or MDS, (\< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification with an intermediate 2 (INT-2) or high-risk score (ie, ≥ 1.5) as assessed by the International Scoring System (IPSS) after failure of hypomethylating agent-based therapy. Based on 3 completed studies and xenograft models, Vosaroxin is hypothesized to be safe and will effective in this patient population.

Detailed description:
This is a phase 1-2, dose escalation study of the safety and clinical activity of vosaroxin in subjects with INT-2 or high risk MDS who have failed prior hypomethylating agent based therapy. The study will utilize a standard 3+3 design to estimate the MTD \[maximum tolerated dose\] for vosaroxin administered to subjects with MDS. MTD will be defined as the highest dose level at which no more than 33% of the subjects observed at a given dose level experience a DLT \[dose limiting toxicity\]. Subjects will be assessed for safety and DLT in the first cycle of vosaroxin. Subjects will be enrolled into the study in cohorts of 3. Three eligible subjects will be enrolled in sequential cohorts at increasing dose levels until at least 1 DLT is observed during the first cycle of vosaroxin therapy. Subjects who receive both doses of vosaroxin will be evaluated for the MTD, DLTs, and safety profile during the first cycle of therapy. Once the MTD has been determined, an expanded evaluation of safety and hematologic response or improvement rate at this dose level will be conducted in additional subjects so that the total number of subjects exposed to this dose level is up to 15 subjects, inclusive of those treated at this dose level in the dose-escalation phase. The exposure of additional subjects at the MTD will provide a better estimate of the toxicity rate. Subjects with a documented response of Complete Response, Partial Response, or hematologic improvement at the end of Cycle 2 may continue to receive vosaroxin for additional cycles at the discretion of the treating investigator and after discussion with the medical staff at Sunesis Pharmaceuticals. There will be a 30-day follow-up period following the termination of study drug treatment.

Arms:
arm 1: All patients will receive vosaroxin according to the dose cohort in which they are enrolled.

Interventions: intervention 1: Vosaroxin
Intervention descriptions: intervention 1: Dose level 1: Vosaroxin 50 mg\^m2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg\^m2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg\^m2 IV on Days 1, 4, 8 and 11 of 28 day cycle

Protocol document: