Dose-escalation Study of Oral Administration of S 055746 in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome

Inclusion Criteria: * Women or men aged \>= 18 years * Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML excluding acute promyelocytic leukaemia: * with relapsed or refractory disease or * \> or = 65 years not previously treated for AML, who are not candidates for intensive chemotherapy or not candidates for standard chemotherapy * Patients with cytologically confirmed and documented MDS or non proliferative Chronic Myelomonocytic Leukaemia (CMML) in relapse or refractory after previous treatment line including at least one hypomethylating agent therapy: * with high or very high risk MDS and without established alternative therapy * transformed to AML and without established alternative therapy * Ability to swallow oral tablet(s) * World Health Organization (WHO) performance status 0-2 * Circulating white blood cells \< or = 30 x 10\^9 /L and \< or = 13 x10\^9 for non proliferative CMML * Adequate renal and hepatic functions * Negative serum pregnancy test within 7 days prior to the first day of study drug administration * Patients must use effective contraception * Written informed consent Exclusion Criteria: * Foreseeable poor compliance to the study procedures * Legally incapacitated person under guardianship or trusteeship * Pregnant or breast-feeding women * Participation in therapeutic interventional study involving investigational drug intake at the same time or within 2 weeks or at least 5 half-lives or patient already enrolled * Previous treatment with a BH3 mimetic * Patients who have not recovered to baseline or CTCAE\< or = Grade 1 from toxicity due to all prior therapies received for the studied disease * Any previous anti-leukaemic treatment for the studied disease within at least 5 half-lives or 2 weeks (hydroxycarbamide permitted) * Any radiotherapy within 4 weeks before first intake (except palliative radiotherapy at localized lesions) * Major surgery within 3 weeks before first intake of S 055746 * Allogenic stem cell transplant within 6 months before the first intake of S 055746 and for patients who still need immunosuppressive treatment * Leukaemic leptomeningeal or leukaemic central nervous system involvement * Concomitant uncontrolled infection, organ dysfunction or medical disease likely to interfere with evaluation of S 055746 safety or study outcome * Human immunodeficiency virus (HIV) infection, hepatitis B or active hepatitis C infection * Within 6 months prior to the first intake of S 055746, history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, and/or stenting, ischemic/haemorrhagic stroke, atrial fibrillation, digestive haemorrhagic risk, deep venous/arterial thromboembolic complication or bleeding diathesis * Decreased Left Ventricular Ejection Fraction (LVEF) * QTcF prolongation * Patients who are receiving QT prolonging drug * Coagulopathies with increased risk of bleeding complications * Other malignancy within 2 years prior to the first intake * Strong or moderate CYP3A4 inhibitors or inducers (treatment, food or drink products) within 7 days prior to the first intake * Treatment highly metabolised by the CYP3A4 or CYP2D6 and/or with a narrow therapeutic index, multi-enzymes and/or OATP and/or P-gp substrates or herbal products within 7 days prior to the first intake. * Patients receiving proton pump inhibitor * Patients having received anticoagulant oral drugs, aspirin \> 325 mg/day and antiplatelets within 7 days prior to first S 055746 intake