This phase I trial is evaluating the combination of a new intravenous drug (S64315) and an oral chemotherapy drug (venetoclax) in patients with Acute Myeloid Leuakemia (AML)An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315 a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia

Inclusion

1. Male or female aged ≥ 18 years;

2. Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):

   • 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 therapy
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
4. Able to comply with study procedures

5. Adequate renal function within 7 days before the inclusion of the patient defined as:

   • Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2

6. Adequate hepatic function within 7 days before the inclusion of the patient defined as:

   • AST and ALT ≤ 1.5 x ULN
   • Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN