ISRCTN73586707TerminatedPhase 1
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)
Institut de Recherches Internationales Servier (France)0 sites80 target enrollmentStarted: September 4, 2014Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 80
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional
Eligibility Criteria
- Sex
- All
Inclusion Criteria
- •Current inclusion criteria as of 13/01/2017:
- •1. Women or men aged >= 18 years
- •2. Patients with cytologically confirmed and documented de novo, secondary or therapy¬related AML excluding acute promyelocytic leukaemia :
- •2.1. With relapsed or refractory disease without established alternative therapy or
- •2.2. > or = 65 years not previously treated for AML, who are not candidates for intensive chemotherapy or not candidates for standard chemotherapy
- •3. Patients with cytollogically confirmed and documented MDS or non-proliferative Chronic Myelomonocytic Leukaemia (CMML) patients, in relapse or refractory after previous treatment line including at least one hypomethylating agent (5-azacytidine or decitabine):
- •3.1. With high or very high risk MDS and without established alternative therapy
- •3.2. Transformed to AML and without established alternative therapy
- •4. Ability to swallow oral tablet(s)
- •5. WHO performance status 0-2
- •6. Circulating white blood cells < or = 30 x 10^9 /L and < or = 13 x 10^9/L for non-proliferative CMML
- •7. Adequate renal and hepatic functions
- •8. Negative serum pregnancy test within 7 days prior to the first day of study drug administration
- •9. Patients must use effective contraception
- •10. Written informed consent
- •Previous 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
Exclusion Criteria
- •Current exclusion criteria as of 14/03/2018:
- •1. Foreseeable poor compliance to the study procedures
- •2. Legally incapacitated person under guardianship or trusteeship
- •3. Pregnant or breastfeeding women
- •4. 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
- •5. Previous treatment with a BH3 mimetic
- •6. Patients who have not recovered to baseline or CTCAE< or = Grade 1 from toxicity due to all prior therapies received for the studied disease
- •7. 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
- •8. Any radiotherapy within 4 weeks before first intake
- •9. Major surgery within 3 weeks before first intake of S 055746
- •10. Allogenic stem cell transplant within 6 months before the first intake of S 055746 and for patients who still need immunosuppressive treatment
- •11. Leukaemic leptomeningeal or leukaemic central nervous system involvement
- •12. Concomitant uncontrolled infection, organ dysfunction or medical disease likelty to interfere with evaluation of S 055746 safety or study outcome
- •13. Human immunodeficiency virus (HIV), hepatitis B or active hepatitis C infection
- •14. 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
- •15. Decreased Left Ventricular Ejection Fraction (LVEF)
- •16. QTcF prolongation
- •17. Patients who are receiving QT prolonging drug
- •18. Coagulopathies with increased risk of bleeding complications
- •19. Other malignancy within 2 years prior to the first intake
- •20. Strong or moderate CYP3A4 inhibitors or inducers (treatment, food or drink products) within 7 days prior to the first intake
- •21. 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.
- •22. Patients receiving proton pump inhibitor
- •23.Patients having received anticoagulant oral drugs, aspirin > 325 mg/day and antiplatelets within 7 days prior to first S 055746 intake
- •Current exclusion criteria as of 13/01/2017:
- •1. Foreseeable poor compliance to the study procedures
- •2. Legally incapacitated person under guardianship or trusteeship
- •3. Pregnant or breastfeeding women
- •4. 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
- •5. Previous treatment with a BH3 mimetic
- •6. Patients who have not recovered to baseline or CTCAE< or = Grade 1 from toxicity due to all prior therapies received for the studied disease
Investigators
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