cancer of the blood leucaemia
Conditions
Interventions
After 14-days screening period, eligible patients will be include in the
study. When enrolled in the study, patients will start their first cycle of
treatment. Bone marrow aspiration and/or medullar
Sponsors
Servier R&D Benelux
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female aged * 18 years old. 2. Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML excluding acute promyelocytic leukaemia: * with relapsed or refractory disease without established alternative therapy or * secondary to MDS treated at least by hypomethylating agent and without established alternative therapy or * > 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative chemotherapy Or Patients with cytologically confirmed and documented MDS in relapse or refractory after previous treatment line including at least one hypomethylating agent and have *10% bone marrow blasts and who are not candidates for any established alternative therapy. 3. ECOG performance status 0 to 2 4. Circulating white blood cells
Exclusion criteria
Exclusion criteria: 12. Unlikely to cooperate in the study. 13. Participant already enrolled in the study who has received at least one S64315 infusion. 14. Pregnancy, breastfeeding or possibility of becoming pregnant during the study 15. Participation in another interventional study requiring investigational treatment intake within 2 weeks or at least 5 half-lives (whichever is longer) prior to first dose of S64315 (participation in non-interventional registries or epidemiological studies is allowed). 16. Presence of * CTCAE grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to NCI-CTCAE, version 4.03 17. Known carriers of HIV antibodies, 18. Known history of significant liver disease, 19. Uncontrolled hepatitis B or C infection, 20. Known active or chronic pancreatitis, 21. History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment, 22. Clinically significant cardiac arrhythmias, complete left bundle branch block, high-grade AV block 23. Troponin (I/T) > ULN, 24. LVEF 450 ms for male and > 470 ms for female, 26. Clinically active severe skin diseases, 27. Any clinically significant medical condition or laboratory abnormality likely to jeopardize the patient*s safety or to interfere with the conduct of the study, in the investigator*s opinion, 28. Active central nervous system disease, 29. Unresolved diarrhea CTCAE grade 2 or higher or presence of medical condition associated with chronical diarrhea (such as irritable bowel syndrome, inflammatory bowel disease) 30. Patients with coagulopathy that will increase the risk of bleeding complications according to investigator*s judgment 31. Allogenic stem cell transplant within 3 months before the first dose of S64315 and for patients who still receive immunosuppressive treatment, 32. Major surgery (involving a risk to the life of the patient) within 2 weeks before the first dose of S64315, or patients who have not recovered from side effects of the surgery, 33. Any previous anti-neoplastic treatment for the studied disease at least 5 half-lives of this treatment prior to first dose of S64315 (except for hydroxycarbamide), 34. Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study entry; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type, 35. Any radiotherapy within 2 weeks before the first dose of S64315 (except for palliative radiotherapy at localised lesions), 36. Prior treatment with an Mcl-1 inhibitor, 37. Patients receiving treatment with medications listed in Section 6.3.1 and that cannot be discontinued at least 1 week prior to start of the study treatment and during the study treatment period. 38. Patients with known hypersensitivity to 64315 including eggs, to soybean or to the excipients of the liposomal vehicle 39. Patients re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the safety profile and tolerability of S64315 in patients with AML, and MDS and to determine the RP2D. (DLT during the first cycle of treatment, incidence and severity of AEs and SAEs, lab results, vital signs, ECG parameters, LVEF assessment, dose interruptions or reductions,..) | — |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacokinetics profile of S64315 will be determined and the preliminary anti-neoplastic activity of S64315 will be assessed. The pharmacodynamics profile of S64315 will be assessed (biological activity of S64315: kinetic assessment of blast reduction), the relation between the expression of Bcl-2 family members in blasts and the anti-neoplastic activity of S64315 (Bcl-2 family members expression), the relationship between the anti-neoplastic activity of S64315 and genomic aberrations in the Bcl-2 gene family and other cancer related genes (somatic alterations and expression of Bcl-2 gene family and a panel of cancer-related genes). Identification of genetic abnormalities potentially induced by S64315 (karyotype analysis). | — |
Countries
Netherlands
Outcome results
None listed