Study of the Relationship Between the Pharmacokinetics (PK) and Pharmacodynamics of Venetoclax in Patients With Acute Myeloblastic Leukemia

Centre Leon Berard100 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

100

Conditions

Acute Myeloid Leukemia

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 must be affiliated or benificiary of a social security system. Exclusion Criteria: * 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 * Any condition that contraindicates blood sampling procedures required by the protocol * Any psychological, family, geographical, or social situation that, according to investigator's judgment, could potentially prevent the signing of an informed consent form and/or woulld likely interfere compliance with study procedures. * Patient under curatorship, guardianship or judicial protection * Pregnant or breast-feeding female patient.

Outcomes

Primary Outcomes

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

Time frame: From the first day of venetoclax administration to end of the treatment (days)

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

Time frame: From the first day of venetoclax administration to end of the treatment (days)

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

Time frame: From the first day of venetoclax administration to end of the treatment (days)

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

Time frame: From the first day of venetoclax administration to end of the treatment (days)

Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Clinical Endpoint

Proportion of patients with a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) or partial remission (PR) or no remission

Time frame: From the first day of venetoclax administration up to day 28 (end of the first venetoclax cure)

Secondary Outcomes

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).

Time frame: From the first day of venetoclax administration and through study completion, at least 24 months

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

Time frame: From the the first day of venetoclax administration to the last day (Day 168) of venetoclax 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

Time frame: From the first day of ventoclax administration and nd through study completion, at least 24 months

Study of the Relationship Between the Pharmacokinetics (PK) and Pharmacodynamics of Venetoclax in Patients With Acute Myeloblastic Leukemia

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts