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

NCT ID: NCT02920541

Last Updated: 2019-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-05-24

Brief 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.

Conditions

Acute Myeloid Leukaemia (AML); Myelodysplastic Syndrome (MDS)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

S 055746

Group Type: EXPERIMENTAL

S 055746

Intervention Type: DRUG

S 055746, per os administration, from 50 to 2000 mg once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.

Interventions

S 055746

S 055746, per os administration, from 50 to 2000 mg once a day during a 21-day cycle. Participants will receive 21-day cycles of treatment until a discontinuation criterion is met.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Wei, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Locations

The Alfred Hospital

Melbourne, , Australia

Royal Melbourne Hospital

Parkville, , Australia

Institut Paoli Calmettes

Marseille, , France

Hôpital Saint Louis

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Countries

Australia; France

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: study-level clinical trial data

View Document

Document Type: Clinical Study Report

View Document

Other Identifiers

2014-002559-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN73586707

Identifier Type: REGISTRY

Identifier Source: secondary_id

CL1-055746-002

Identifier Type: -

Identifier Source: org_study_id