Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Not provided at time of registration and not expected to be available in the future

Trial website

Contact information



Primary contact

Prof Andrew Wei


Contact details

Department of Haematology
The Alfred Hospital Commercial Road
VIC 3004

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Phase 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)


Study hypothesis

To determine the safety profile and tolerability of S 055746 and establish the recommended Phase II dose

Ethics approval

Ethics approval was obtained before recruitment of the first participants

Study design

Phase I dose-escalation study

Primary study design


Secondary study design


Trial setting


Trial type


Patient information sheet

Not provided at time of registration


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


Film-coated tablets containing 50 mg or 100mg of S055746. This trial is a dose escalation trial. A modified version of the Continual Reassessment Method (mCRM) will be used for dose allocation process. The first daily dose tested will be 100 mg, and then a panel of daily doses from 50 to 1000 mg could be tested according to the dose allocation process of the mCRM. Doses over 1000 mg and intermediate doses could be proposed depending on available results during the study. Treatment duration for the participant is until evidence of treatment failure, the occurrence of unacceptable toxicity, death, exercise of investigator discretion, withdrawal of consent or if clinically indicated after discussion between investigator and the sponsor on a case by case basis

Intervention type



Phase I

Drug names


Primary outcome measures

Dose Limiting Toxicities in cycle 1.
Maximum Tolerated Dose defined as the highest dose administered in the study at which the incidence of DLT is 30%.
Safety profile at each visit assessed by Adverse events monitoring, laboratory tests, vital signs and performance status, clinical examination and ECG parameters.

Secondary outcome measures

Pharmacokinetics parameters on blood sample during cycles 1 and 2 PD parameters on blood, BMA and biospy if available from cycle 1 to cycle 3 and in any time in case of suspicion of disease progression optional pharmacogenomics analysis on Cycle 1, D1 pre-dose. Preliminary anti-leukaemic activity of S055746 throughout the study (blood, BMA and biopsy if available)

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Women or men aged >= 18 years
2. Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML excluding APL, with relapsed or refractory disease or > or = 65 years not previously treated, who are not candidates for intensive chemotherapy or not candidates for standard chemotherapy
3. Patients with cytollogically confirmed and documented high or very high risk myelodysplastic syndrome who have failed prior hypomethylating therapy
4. Who performance status 0-2
5. Circulating white blood cells < or = 30 x 10^9 /L
6. For MDS patients:
6.1. Platelets count > 25 10^9/L
6.2. Neutrophils > 0.5 10^9/L
7. Acceptable coagulation parameters according to local laboratory
8. Adequate renal and hepatic functions
9. Negative serum pregnancy test within 7 days prior to the first day of study drug administration
10. Patients must use effective contraception

Participant type


Age group




Target number of participants

60 to 80 patients

Participant exclusion criteria

1. Pregnant or breast-feeding women
2. Involvement in therapeutic interventional study at the same time or within 2 weeks prior to first S 055746 intake or patient already enrolled in the study
3. Previous treatment with a BH3 mimetic
4. Patients who have not recovered to baseline or CTCAE< or = Grade 1 from toxicity due to all prior therapies
5. Any previous anti-leukaemic treatment (AML, high or very high risk MDS) within at least 5 half lives or 2 weeks prior to the study entry except for hydroxyurea
6. Any radiotherapy within 4 weeks before first intake
7. Major surgery within 3 weeks before first intake of S 055746
8. Allogenic stem cell transplant within 6 months before the first intake of S 055746 and for patients who still need immunosuppressive treatment
9. Leukaemic leptomeningeal or leukaemic central nervous system involvement
10. Concomitant uncontrolled infection, organ dysfunction or medical disease likelty to interfere with evaluation of S 055746 safety or study outcome
11. Human immunodeficiency virus (HIV)
12. 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/haemorragic stroke, atrial fibrillation, digestive haemorrhagic risk, deep venous/arterial thromboembolic complication or bleeding diathesis
13. QTc prolongation
14. LVEF assessed by echocardiography or Multi-Gated Acquisition scan (MUGA scan)
15. Treatment, food or drink products known to inhibit or induce CYP3A4 within 7 days prior to the first intake
16. Treatment highly metabolised by the CYP3A4 and with a narrow therapeutic index within 7 days prior to the first intake.

Recruitment start date


Recruitment end date



Countries of recruitment

Australia, France

Trial participating centre

Department of Haematology
VIC 3004

Sponsor information


Institut de Recherches Internationales Servier (France)

Sponsor details

50 rue Carnot

Sponsor type




Funder type


Funder name

Institut de Recherches Internationales Servier (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes