S055746: This phase I trial is assessing the oral administration of the drug S 055746 in patients with Acute Myeloid Leukaemia or Myelodysplastic SyndromePhase I dose-escalation study of the orally administrered selective Bcl-2 inhibitor S055746 as monotherapy for the treatment of patients with Acute Myeloid Leukaemia (AML) or high or very high risk Myelodysplastic Syndrome (MDS)

Exclusion

• 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