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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02920541




Registration number
NCT02920541
Ethics application status
Date submitted
23/08/2016
Date registered
30/09/2016

Titles & IDs
Public title
Dose-escalation Study of Oral Administration of S 055746 in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome
Scientific title
Phase I Dose-escalation Study of the Orally Administered Selective Bcl-2 Inhibitor S 055746 as Monotherapy for the Treatment of Patients With Acute Myeloid Leukaemia (AML) or High or Very High Risk Myelodysplastic Syndrome (MDS)
Secondary ID [1] 0 0
2014-002559-24
Secondary ID [2] 0 0
CL1-055746-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia (AML) 0 0
Myelodysplastic Syndrome (MDS) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - S 055746

Experimental: S 055746 -


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [1] 0 0
During cycle 1 (21 days)
Primary outcome [2] 0 0
Incidence of Adverse Events (AEs)
Timepoint [2] 0 0
From first dose until 30 days after the last dose intake
Secondary outcome [1] 0 0
Plasma concentration of S 055746
Timepoint [1] 0 0
Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8
Secondary outcome [2] 0 0
The pharmacokinetic (PK) profile of S 055746: Area Under the Curve [AUC]
Timepoint [2] 0 0
Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8
Secondary outcome [3] 0 0
The PK profile of S 055746: Maximal Concentration [Cmax]
Timepoint [3] 0 0
Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8
Secondary outcome [4] 0 0
Best Response Rate (BRR)
Timepoint [4] 0 0
Up to study completion (maximum of 3 years)
Secondary outcome [5] 0 0
Progression Free Survival (PFS)
Timepoint [5] 0 0
From date of inclusion until the date of progression or date of death, whichever occurs first, assessed up to study completion (maximum of 3 years)
Secondary outcome [6] 0 0
Event Free Survival (EFS)
Timepoint [6] 0 0
From date of inclusion until the date of progression or date of death or discontinuation of treatment, whichever occurs first, assessed up to study completion (maximum of 3 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/05/2018
Sample size
Target
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Marseille
Country [2] 0 0
France
State/province [2] 0 0
Paris
Country [3] 0 0
France
State/province [3] 0 0
Pierre Bénite

Funding & Sponsors
Primary sponsor type
Other
Name
Institut de Recherches Internationales Servier
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ADIR, a Servier Group company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andrew Wei, MBBS, PhD
Address 0 0
The Alfred
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

* submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
After Marketing Authorisation in EEA or US if the study is used for the approval.
Available to whom?
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicaltrials.servier.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02920541