Trial purpose
Cancer treatment
Tumor type
Haematological
Age
18+
Clinical summary
Summary
To determine the safety profile and tolerability of S 055746 and establish the recommended Phase II dose. 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
Conditions
This trial is treating people with Acute Myeloid Leukaemia, Myelodysplasia
Eligibility
Inclusion
- 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
- 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
Inclusion
- You have had treatment, but your cancer has come back (relapsed or recurrent).
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
- You are able to swallow medication by mouth.
Exclusion
- You are currently being treated on a clinical trial.
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov, UK’s Clinical Study Registry *. View further details about this trial on the registry via the links below:
Trial sponsor
Servier
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)
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