Study of Clinical Efficacy and Safety of Tosedostat in MDS

Inclusion Criteria

• Able to understand and to provide written informed consent
• At least 18 years of age with pathologically confirmed MDS ( 5% BMBL
• For patients with 5-10% BMBL, ≥ 50% increase in BMBL to >10% BMBL
• For patients with 10-20% BMBL, ≥ 50% increase in BMBL to >20% BMBL
• For patients with 20-30% BMBL, ≥ 50% increase in BMBL to >30% BMBL
• Any of the following:
• ≥ 50% decrease from maximum remission/response levels in granulocytes or PLT
• Decrease in Hgb concentration by ≥2 g/dL
• Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values 160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy
• Clinically significant atrial fibrillation * Grade 3/4 in the CTCAE v4.0 grading would generally be considered clinically significant, although this remains a judgment for the Investigator to make.
• LVEF ≤ 50%
• Baseline troponin I and b-type natriuretic peptide > Grade I
• Prior exposure cardiotoxic agent, such as anthracycline, within 3 months of enrollment
• Concomitant use of drugs that prolong QT/QTc interval except antibiotics, antifungals, and other antimicrobials used as standard of care for the treatment and prevention of infection and/or other such drugs clinically indicated for patient care. When use of concomitant medications with QT-prolonging potential is necessary, ECG must be repeated 4 hours post-dose on Day 1, on Day 3, and on Day 7, and as clinically indicated, relative to start of agent with QT-prolonging potential.
• Gastrointestinal disorders that may interfere with absorption of drug
• Active serious infection or sepsis
• Clinically significant interstitial lung disease