The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Unlikely to cooperate in the study.
• Participant already enrolled in the study who has received at least one S64315 infusion.
• Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
• 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).
• Presence of ≥ CTCAE grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.03)
• Unresolved ≥ CTCAE grade 2 diarrhoea or medical conditions associated with chronic diarrhoea (such as irritable bowel syndrome, inflammatory bowel disease)
• Known carriers of HIV antibodies
• Known history of significant liver disease
• Uncontrolled hepatitis B or C infection
• Known active or chronic pancreatitis
• History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment.

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

After Marketing Authorisation in EEA or US if the study is used for the approval.

Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.