S64315: This phase I trial is evaluating an intravenously administered drug (S64315) for the treatment of Acute Myeloid Leukaemia (AML) or Myelodysplastic SyndromePhase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)

Inclusion

• Male or female aged ≥ 18 years;

• Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, 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 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;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Circulating white blood cells < 10^9 /L (with or without use of hydroxycarbamide).

• Adequate renal function defined as:

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

• LDH < 2 x ULN

• Adequate hepatic function defined as:

  • AST and ALT ≤ 1.5 x ULN
  • Total bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome (confirmed by the UGT1A1 polymorphism analysis), who are excluded if total bilirubin>3.0 x ULN or direct bilirubin > 1.5 x ULN
• Serum CK/CPK ≤2.5 x ULN.