Venetoclax Resistance Landscape in Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to collect medical informations and samples from refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax treatment, in order to evaluate the frequency of resistance mechanisms.

Detailed Description
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The purpose of this study is to collect medical informations and samples (blood, bone marrow and/or lymph node) from refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax treatment, in order to evaluate the frequency of resistance mechanisms (BCL2 mutations, over-expression of other members of the BCL2 protein family and energy metabolism changes).

Official Title
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Venetoclax Resistance Landscape in Chronic Lymphocytic Leukemia

Conditions
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CLL, Chronic Lymphocytic Leukemia, Progressive Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia, Relapsed Chronic Lymphocytic Leukemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years old; chronic lymphocytic leukemia diagnosis according to iwCLL criteria; refractory and/or relapsed disease during or after venetoclax treatment; tumor samples available. Relapse might be progressive chronic lymphocytic leukemia or transformation into Richter syndrome. Patients must be able to express their opposition to be enrolled in this study, if need be. Patients must be affiliated at the French Social Security system Exclusion Criteria: Patients of their legal guardians refusing to participate -

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax<br>Cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency measurement of BCL2 gene mutations | Frequency measurement of BCL2 gene mutations in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy | immediately after the chronic lymphocytic leukemia progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency measurement of 1q amplification | Frequency measurement of 1q amplification in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy | immediately after the chronic lymphocytic leukemia progression | 
| Differential expression of candidate transcripts and proteins | Differential expression of candidate transcripts and proteins (BCL2 protein family, AMP signaling pathway, energy metabolism) in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy | immediately after the chronic lymphocytic leukemia progression | 
| Correlation of resistance mechanisms with clinical staging | Correlation of resistance mechanisms (BCL2 mutation and 1q amplification) with clinical staging, in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy | immediately after the chronic lymphocytic leukemia progression | 
| Correlation of resistance mechanisms with genomic chronic lymphocytic leukemia features | Correlation of resistance mechanisms (BCL2 mutation and 1q amplification) with genomic chronic lymphocytic leukemia features, in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy | immediately after the chronic lymphocytic leukemia progression | 
| Progression Free Survival according to resistance mechanisms | Progression Free Survival according to resistance mechanisms (BCL2 mutation and 1q amplification), in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy | immediately after the chronic lymphocytic leukemia progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venetoclax, Venetoclax resistance, Resistance mechanism