Determinants of the Response to BTK Degraders (BTKd) in Chronic Lymphocytic Leukemia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Non-Interventional Sample Collection and Analysis.
- Who it may be relevant to
- Registry conditions: Chronic Lymphocytic Leukemia, BTK Degraders. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The aim of the REBELLE cohort - bio-collection is to collect samples from patients with Chronic Lymphocytic Leukemia candidates or those exposed to BTK degraders to evaluate the mechanisms of resistance to these new molecules. To do this, an additional blood or bone marrow sample to those planned in the context of patient care or a residual lymph node biopsy sample will be collected after signing consent.
Detailed description
Chronic Lymphocytic Leukemia (CLL) is a malignant hematological disease of B cells, primarily observed in older adults. Although it is classified among indolent hematological malignancies, CLL exhibits significant heterogeneity, both in terms of its biological characteristics and its disease progression and the therapeutic strategies employed. In patients requiring treatment, the disease can relapse. Until recently, immunochemotherapy remained the standard treatment for this disease, but the last decade has seen the emergence of oral targeted therapies, such as Bruton's tyrosine kinase inhibitors (BKT1s) and BCL-2 inhibitors (BCL-2 inhibitors), which have profoundly altered patient prognosis. While the introduction of these two classes of drugs has led to improved prognosis, a rare but significant subgroup of patients, known as "double refractory," has emerged. These patients, exposed to both BKT and BCL-2 inhibitors and who have become refractory to both treatments, have a poor prognosis. To overcome this problem of resistance, molecules targeting the degradation of the BTK protein (BTKd) are currently under development. The main investigator propose the creation of a cohort and a biobank of samples from CLL patients who are candidates for or have been exposed to BTKd, in order to study the mechanisms of response and resistance to these molecules.
Interventions
- Other Non-Interventional Sample Collection and Analysis
This study is observational. Biological samples are collected as part of standard care or for research purposes and analyzed to characterize resistance mechanisms. No treatment or intervention is administered as part of the study protocol.
Primary outcome measures
- Characterization of resistance mechanisms to CLL patients candidates or exposed to BTKd. [Time frame: Up to 5 years after inclusion]
Secondary outcome measures (7)
- Development of preclinical ex vivo culture models [Time frame: Up to 5 years after inclusion]
- Genetic modification of primary CLL cells [Time frame: Up to 5 years after inclusion]
- Genomic data analysis to identify resistance-related genes [Time frame: Up to 5 years after inclusion]
- Pharmacological targeting of novel candidate molecules [Time frame: Up to 5 years after inclusion]
- Generation of knockout cell lines for genes of interest [Time frame: Up to 5 years after inclusion]
- Generation of drug-resistant cell lines and comparative RNA sequencing [Time frame: Up to 5 years after inclusion]
- Reconstruction of the tumor microenvironment using co-culture systems [Time frame: Up to 5 years after inclusion]
Eligibility criteria
Inclusion criteria
- Patient with CLL candidates ou exposed to BTKd
- Patient who has provided informed consent to participate in the study.
- Patient covered by a social security health insurance plan
Exclusion criteria
- Minor patients.
- Adults under guardianship.
- Protected persons.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 14 centers
- CHU de Angers — Angers
- CHU de Bordeaux — Bordeaux
- Institut Bergonié — Bordeaux
- CHU de Clermont-Ferrand — Clermont-Ferrand
- CHD Vendée — La Roche-sur-Yon
- Centre Léon Bernard — Lyon
- Institut Paoli-Calmettes (Marseille) — Marseille
- CHU de Montpellier — Montpellier
- … and 6 more centers
Identifiers
NCT: NCT07099443 · RC25_0135 · 2025-A00697-42