Phase I / II, Open Label, Dose Escalation Part (Phase I) Followed by Non-comparative Expansion Part (Phase II), Multi-centre Study, Evaluating Safety, Pharmacokinetics and Efficacy of S65487, a Bcl2 Inhibitor Combined With Azacitidine in Adult Patients With Previously Untreated Acute Myeloid Leukemia Not Eligible for Intensive Treatment

CL1-65487-003

The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S65487 with azacitidine in patients with acute myeloid leukaemia.

2021-03-10

2024-09-30

2025-04-30

Active (not recruiting)

Early phase I

57

Inclusion Criteria: * Male or female participant aged ≥ 18 years old * Participants with cytologically confirmed and documented treatment naïve, de novo or secondary AML defined by WHO 2016 classification (Arber, 2016). Secondary AML includes: * Previous myelodysplastic syndrome transformed * AML due to exposure to potentially leukemogenic therapies or agents (e.g. radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 3 years * Participants not eligible for standard induction chemotherapy * Aged ≥ 75 years old * Or Age ≥18 years with at least one of the following comorbidities: * Clinically significant heart or lung comorbidities, as reflected by at least one of: * Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected * Forced expiratory volume in 1 second (FEV1) ≤65% of expected * Other contraindication(s) to anthracycline therapy (must be documented) * Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented * ECOG (Eastern Cooperative Oncology Group) performance status should be (criterion should be rechecked at inclusion visit) ECOG ≤ 2. * Written informed consent obtained prior any study-specific procedure as described in section 13.3 of the protocol. * Adequate renal and hepatic function * Circulating White Blood Cell Count (WBC count) \< 25\*109 G/L (with or without use of hydroxycarbamide/leukapheresis) * Serum potassium, serum calcium, serum phosphates, serum magnesium within normal limits with or without supplementation. Exclusion Criteria: * Major surgery within 3 weeks prior to the first IMP administration, or participants who have not recovered from side effects of the surgery * Any radiotherapy within 3 weeks before the first IMP administration, * Allogenic stem cell transplant within 3 months before the first IMP administration and/or participants with active Graft-versus-host disease within 3 months before the first IMP administration and/or participants who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or participant who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration * Acute promyelocytic leukemia (APL, French-American-British M3 classification) * Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 3, 2019 for Acute Myeloid Leukemia * Treatment with hypomethylating agents (decitabine/azacitidine) or Venetoclax for AHD (antecedent hematologic disorders) in the 3 months prior to the first IMP intake

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2024-06-07