Plasma Dosage of Venetoclax in the Fup of AML Patients Treated With Aza + Ven

Study Overview
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Brief Summary
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The study proposes to correlate the plasma dosage of VEN with the inhibition of its Bcl-2 target during the first treatment cycle. VEN will be measured sequentially during the first treatment cycle and assess inhibition of its target by measuring the level of phosphorylation of Bcl-2 serine 70. In parallel, BH3 profiling will be evaluated sequentially. All these analyses will be correlated with treatment toxicity, response rate and overall patient survival. This pilot study will highlight the inter-individual variability of this AZA + VEN combination, and enable to launch a national study via the national cooperative groups to validate the results and thus ultimately propose a personalized treatment for patients benefiting from this combination.

Official Title
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Plasma Dosage of Venetoclax in the Follow-up of Acute Myeloid Leukemias Ineligible for Intensive Chemotherapy in the First Line of Treatment and Treated With Azacitidine + Venetoclax. Pilot Study VENETACIBLE

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Other: Pharmacokinetic sampling
* Other: Vital status determination
* Other: Toxicity assessments
* Drug: Venetoclax and azacitidine combination


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Patient with acute myeloid leukemia (AML) not eligible for intensive chemotherapy Patients aged 18 or over Patient treated with the combination azacitidine (AZA) + venetoclax (VEN) Patient having signed the study informed consent form Patient with social security coverage Exclusion criteria : Patients receiving treatment inhibiting or inducing Cytochrome CYP3A4 Presence of an active, uncontrolled infection Patient participating or having participated in a clinical drug trial in the month prior to inclusion. Vulnerable persons

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AML patients ineligible for intensive chemotherapy and treated with azacitidine and venetoclax<br>Newly diagnosed AML patients | Other: Pharmacokinetic sampling<br>* 4 blood withdrawals ( before treatment, Day 5, Day 9 and relapse or 12 months after start of treatment) for the plasma dosage of VEN and inhibition of its Bcl-2<br>Other: Vital status determination<br>* Survival situation 12 months after start of treament<br>Other: Toxicity assessments<br>* Toxicity events<br>Drug: Venetoclax and azacitidine combination<br>* Response to treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic dosage | Correlation of VEN plasma levels with inhibition of its Bcl-2 target | Before treatment | 
| Plasmatic dosage | Correlation of VEN plasma levels with inhibition of its Bcl-2 target | At Day 5 of 1st round of chemotherapies | 
| Plasmatic dosage | Correlation of VEN plasma levels with inhibition of its Bcl-2 target | At Day 9 of 1st round of chemotherapies | 
| Plasmatic dosage | Correlation of VEN plasma levels with inhibition of its Bcl-2 target | At 12 months after start of treatment or at relapse whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Evaluate the overall survival | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute myeloid leukemia, venetoclax, azacitidine