This is a prospective, multicenter, clinical-biological cohort study. Its objective is to assess the pharmacokinetics-pharmacodynamics (PK-PD) of venetoclax (VEN) in patients with Acute Myeloid Leukemia (AML).
This study involves only minimal risks and constraints related to the collection of biological samples (blood samples for PK testing) and the collection of clinical data. Therapeutic management of patients participating in this study is not changed. A total of 100 patients will be included in the study over a 12-month period. A maximum of 21 additional samples are planned, with a maximum of 12 mL of blood per sampling day (4 mL at each sampling time) for PK dosing of venetoclax.
Male or female patient aged of at least 18 years on day of signing informed consent
Patient with histologically-confirmed diagnosis of Acute Myeloblactic Leukaemia according to classification ELN 2022 (European Leukemia Net 2022)
Patient who has to initiate treatment venetoclax-azacitidine as first line. Note : triple associations with targeted therapy are not authorized
Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed.
Patient with acute promyelocytic leukemia (APL, AML3)
Patient with AML eligible to intensive chemotherapy
Patient previously treaed with venetoclax and/or azacitidine
Patient participating to another clinical trial with a medicinal product
Single group
Pharmacokinetic dosages of venetoclax
Other interventionBlood samples for pharmacokinetic dosing of venetoclax at different endpoints of treatment period
Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Biological endpoint
To assess PK exposure parameters : AUC (area under the curve) of venetoclax at steady state
Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Biological endpoint
To assess PK exposure parameters : Minimal Concentration (Cmin) of venetoclax at steady state
Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Biological endpoint
To assess PK exposure parameters : Peak Plasma Concentration (Cmax) of venetoclax at steady state
Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Biological endpoint
To assess PK exposure parameters : Equilibrium concentration (Css) of venetoclax at steady state
To assess relationship between different PK markers of venetoclax and its clinical efficacy.
Correlation between PK exposure parameters (including Cmin, Cmax, Css) of venetoclax and clinical outcome (cytologic response at cycle 6, survival without progression and overall survival).
To assess correlation between plasmatic exposition to venetoclax and occurrence of adverse events
Correlation between PK exposure parameters (including Cmin, Cmax, Css) of venetoclax and occurence of adverse events grade equal or superior to 3 related to venetoclax/azacitidine and their impact on treatment administration
To assess inter-individual and intra-individual variability in plasma exposure to venetoclax.
Coefficient of variation of AUC and Cmin at steady state for venetoclax
To assess the relationship between plasmatic venetoclax exposition and response to treatment
To assess correlation between minimal concentration of venetoclax and minimal residual disease
To assess the relationship between plasmatic venetoclax exposition and response to treatment
To assess correlation between Peak Plasma Concentration (Cmax) of venetoclax and minimal residual disease
To assess the relationship between plasmatic venetoclax exposition and response to treatment
To assess correlation between Equilibrium concentration of venetoclax (Css) and minimal residual disease
To assess interaction between azole antifungals and venetoclax
Number of patients treated or not treated by an azole antifungal
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Centre Leon Berard
Lead sponsor
Fédération Leucémie Espoir
Collaborator
