Relation Between Venetoclax Plasma Concentration and Remission in Adults with Acute Myeloid Leukemia (PREDICLAX)

Prior treatment

• Subject has already received anticancer treatment (drugs, surgery, radiotherapy) for AML, hematological malignancy or malignant cancer (within the last 2 years).
• Subject has been exposed to potent CYP450 inducers or inhibitors (including grapefruit, Seville oranges) within 7 days prior to treatment initiation.

Other illness

• Subject to an uncontrolled intercurrent disease such as:
  • infection (viral, bacterial or fungal) requiring treatment;
  • symptomatic congestive heart failure;
  • unstable angina pectoris
  • cardiac arrhythmia
  • psychiatric illness or drug addiction that would limit compliance with study requirements (risk of treatment non-adherence or low venous capital).
• Documented hypersensitivity to the drugs used to treat the subject.

Lab values

• blood leukocytes \>25 G/L.

Other

• Subjects with AML with central nervous system involvement or promyelocytic type (AML-M3).

• Subject must have a confirmed diagnosis of previously untreated AML (ELN 2022 criteria) within 28 days of the onset of symptoms. Only previous cytoreductive treatments (e.g. hydroxyurea) are authorized.
• Subject must be ineligible for standard cytarabine and anthracycline induction therapy according to the following criteria:
  • Subject aged ≥ 75 years.
  • OR subject aged between 60 and 74 with at least one of the following comorbidities:
  • ECOG performance status: of 2 or 3.
  • cardiac history: heart failure requiring treatment, left ventricular ejection fraction ≤ 50%, chronic stable angina.
  • carbon monoxide diffusion capacity ≤ 65% or forced expiratory volume in one second ≤ 65%.
  • creatinine clearance between 30 and 45 mL/min/m².
  • liver damage (not related to AML) with total bilirubin between 1.5 and 3 × upper normal limit.
  • any other comorbidity deemed by the physician to be incompatible with standard induction chemotherapy.
• Patients are eligible for the recommended standard treatment, i.e. a combination of venetoclax and a hypomethylating agent.
• Subjects must voluntarily sign and date an informed consent form authorized by the relevant authorities.
• The participation of the subject in another interventional study not interfering with the pathophysiological, pharmacological and clinical rationale of this protocol is possible.