Venetoclax Resistance Landscape in Chronic Lymphocytic Leukemia

Recruiting

• Conditions: Chronic Lymphocytic Leukemia; Relapsed Chronic Lymphocytic Leukemia; Progressive Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; CLL

• Registration Number: NCT05246345
• Lead Sponsor: University Hospital, Clermont-Ferrand

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2021-10-13
• Study First Submitted QC: 2022-02-17
• Study First Posted: 2022-02-18
• Study Start: 2022-03-07
• Status Verified: 2023-06
• Last Update Submitted: 2024-01-08
• Last Update Posted: 2024-01-09
• Primary Completion: 2027-03
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Frequency measurement of BCL2 gene mutations	immediately after the chronic lymphocytic leukemia progression	Frequency measurement of BCL2 gene mutations in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy

Secondary Outcome Measures

Name	Time	Method
Correlation of resistance mechanisms with clinical staging	immediately after the chronic lymphocytic leukemia progression	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
Differential expression of candidate transcripts and proteins	immediately after the chronic lymphocytic leukemia progression	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
Correlation of resistance mechanisms with genomic chronic lymphocytic leukemia features	immediately after the chronic lymphocytic leukemia progression	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
Progression Free Survival according to resistance mechanisms	immediately after the chronic lymphocytic leukemia progression	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
Frequency measurement of 1q amplification	immediately after the chronic lymphocytic leukemia progression	Frequency measurement of 1q amplification in a cohort of refractory and/or relapsed chronic lymphocytic leukemia during or after venetoclax therapy

Trial Locations

Locations (14)

Hopital AVICENNE; 🇫🇷 Bobigny, France

CHU d'Amiens; 🇫🇷 Amiens, France

Hopital Pitié Salpetrière; 🇫🇷 Paris, France

CHU Grenoble; 🇫🇷 Grenoble, France

CHU de Montpellier; 🇫🇷 Montpellier, France

CHU de Reims; 🇫🇷 Reims, France

CHRU de Lille; 🇫🇷 Lille, France

CHU Nancy; 🇫🇷 Nancy, France

IUCT Oncopole; 🇫🇷 Toulouse, France

Centre LEON BERARD; 🇫🇷 Lyon, France

CHU clermont-ferrand; 🇫🇷 Clermont-Ferrand, France

CHU de Clermont Ferrand; 🇫🇷 Clermont-Ferrand, France

CHU de Besançon; 🇫🇷 Besançon, France

Hopital Haut LEVEQUE; 🇫🇷 Pessac, France