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

• Status: Completed
• Trial end date: 2018-05-24
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the safety profile and tolerability of S 055746 in patients with AML, and high or very high risk MDS, in terms of Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile (DLT, MTD), PK profile, PD profile and preliminary efficacy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut de Recherches Internationales Servier
• Collaborator: ADIR, a Servier Group company

Criteria

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