Chronic Lymphocytic LeukemiaREBELLENCT07099443
Determinants of the Response to BTK Degraders (BTKd) in Chronic Lymphocytic Leukemia
An observational study of Chronic Lymphocytic Leukemia and BTK Degraders, run by Nantes University Hospital at 14 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, BTK Degraders
- What is being tested?
- Non-Interventional Sample Collection and Analysis
- How many people
- 60 participants
- Where
- 14 sitesFrance
- Study dates
- 9 Oct 2025to 15 Sep 2039
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Double refractory CLL patients
Who may be able to join
- 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
Who cannot join
- Minor patients.
- Adults under guardianship.
- Protected persons.
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
France14 sites, 14 recruiting
- Not yet recruiting
CHU de Angers
Angers
Aline Clavert, aline.clavert@chu-angers.fr
- Not yet recruiting
CHU de Bordeaux
Bordeaux
Raphaëlle Aubrais, raphaelle.aubrais@chu-bordeaux.fr
- Not yet recruiting
Institut Bergonié
Bordeaux
Fontanet Bijou, f.bijou@bordeaux.unicancer.fr
- Not yet recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand
Romain Guieze, rguieze@chu-clermontferrand.fr
- Recruiting
CHD Vendée
La Roche-sur-Yon
Jessie Bourcier, jessie.bourcier@ght85.fr
- Not yet recruiting
Centre Léon Bernard
Lyon
Anne-Sophie Michallet, anne-sophie.michallet@lyon.unicancer.fr
- Not yet recruiting
Institut Paoli-Calmettes (Marseille)
Marseille
Anne Calleja, callejaa@ipc.unicancer.fr
- Not yet recruiting
CHU de Montpellier
Montpellier
Emmanuelle Tchernonog, e-tchernonog@chu-montpellier.fr
- Not yet recruiting
CH Régional Universitaire de Nancy
Nancy
Pierre Feugier, p.feugier@chru-nancy.fr
- Recruiting
University Hospital
Nantes
Anne LOK, MD, PhD, 02 53 48 28 35, anne.lok@chu-nantes.fr
- Not yet recruiting
Hôpital Avicenne (AP-HP)
Paris
Vincent Levy, vincent.levy@aphp.fr
- Not yet recruiting
Hôpital Universitaire Pitié Salpêtrière de Paris
Paris
Damien Roos Weil, damien.roosweil@aphp.fr
- Not yet recruiting
CHU de Poitiers
Poitiers
Cécile Tomowiak, cecile.tomowiak@chu-poitiers.fr
- Not yet recruiting
Centre Henri-Becquerel de Rouen
Rouen
Stéphane Lepretre, stephane.lepretre@chb.unicancer.fr
About this study
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.
Read the 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.
- Conditions
- Chronic Lymphocytic Leukemia, BTK Degraders
- Being tested
- Non-Interventional Sample Collection and Analysis
- Keywords
- Chronic Lymphocytic Leukemia, Bruton tyrosine kinase inhibitors, BCL-2 inhibitors, BTK degraders
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-Interventional Sample Collection and AnalysisOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Chronic Lymphocytic Leukemia candidates or those exposed to BTKd | Collection of additional samples of blood and bone marrow or residual lymph node biopsy at the time of inclusion (for diagnosis or relapse), month 6 and relapse. Receives: Other: Non-Interventional Sample Collection and Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterization of resistance mechanisms to CLL patients candidates or exposed to BTKd.
The primary outcome is the in-depth characterization of tumor cells and their microenvironment in CLL patients candidates or exposed to BTKd. Analyses will be performed using cellular biology (e.g., flow cytometry), molecular biology (e.g., RNA sequencing), and bioinformatics (e.g., deconvolution). Functional studies include the development of preclinical ex vivo models (2D/3D culture) and gene editing of primary cells using CRISPR/Cas9 technology, based on the expertise of Team 11 at CRCI²NA.
The study will include 60 patients over a 9-year enrollment period. Each participant will be followed for 5 years, resulting in a total study duration of 14 years.
Measured: Up to 5 years after inclusion
Secondary outcomes (7)
Development of preclinical ex vivo culture models
Establishment of 2D and 3D ex vivo culture systems using primary CLL cells to replicate tumor behavior and evaluate functional characteristics.
Measured: Up to 5 years after inclusion
Genetic modification of primary CLL cells
Application of gene editing technologies (e.g., CRISPR/Cas9) to modify primary chronic lymphocytic leukemia cells in order to investigate gene function and resistance pathways.
Measured: Up to 5 years after inclusion
Genomic data analysis to identify resistance-related genes
Comprehensive genomic and transcriptomic profiling of CLL samples to identify genetic alterations and expression patterns associated with resistance to BTK degraders.
Measured: Up to 5 years after inclusion
Pharmacological targeting of novel candidate molecules
Functional validation of newly identified targets through pharmacological inhibition to assess their therapeutic potential in vitro using CLL models.
Measured: Up to 5 years after inclusion
Generation of knockout cell lines for genes of interest
Creation of gene knockout models in CLL cell lines via CRISPR/Cas9 to explore the biological role of specific resistance-associated genes.
Measured: Up to 5 years after inclusion
Generation of drug-resistant cell lines and comparative RNA sequencing
Development of CLL cell lines resistant to BTK degraders followed by RNA sequencing analysis to compare gene expression profiles between drug-sensitive lines and resistant cell lines.
Measured: Up to 5 years after inclusion
Reconstruction of the tumor microenvironment using co-culture systems
Establishment of co-culture models including immune (T lymphocytes, nurse-like cells) and/or stromal cells (from lymph nodes or bone marrow) to mimic the CLL tumor microenvironment.
Measured: Up to 5 years after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start9 Oct 2025
- Primary completion15 Sep 2039 (estimated)
- Study completion15 Sep 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne LOK, MD, PhD, Principal investigator, Hospital of Nantes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07099443
- Sponsor's protocol ID
- RC25_0135
- Other IDs
- 2025-A00697-42
- Acronym
- REBELLE
- Status last verified
- Apr 2026
- First submitted
- 25 Jul 2025
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determinants of the Response to BTK Degraders (BTKd) in Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT07099443
- Acronym / sponsor ID
- REBELLE / RC25_0135
- Conditions
- Chronic Lymphocytic Leukemia, BTK Degraders
- Keywords
- Chronic Lymphocytic Leukemia, Bruton tyrosine kinase inhibitors, BCL-2 inhibitors, BTK degraders
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 9 Oct 2025 (actual)
- Primary completion
- 15 Sep 2039 (estimated)
- Study completion
- 15 Sep 2039 (estimated)
- First posted
- 1 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chronic Lymphocytic Leukemia candidates or those exposed to BTKd | – | Other: Non-Interventional Sample Collection and AnalysisCollection of additional samples of blood and bone marrow or residual lymph node biopsy at the time of inclusion (for diagnosis or relapse), month 6 and relapse. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Double refractory CLL patients
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- Minor patients.
- Adults under guardianship.
- Protected persons.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-Interventional Sample Collection and AnalysisThis 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. | Other | Chronic Lymphocytic Leukemia candidates or those exposed to BTKd |
Primary outcome
Characterization of resistance mechanisms to CLL patients candidates or exposed to BTKd.
Time frame: Up to 5 years after inclusion
The primary outcome is the in-depth characterization of tumor cells and their microenvironment in CLL patients candidates or exposed to BTKd. Analyses will be performed using cellular biology (e.g., flow cytometry), molecular biology (e.g., RNA sequencing), and bioinformatics (e.g., deconvolution). Functional studies include the development of preclinical ex vivo models (2D/3D culture) and gene editing of primary cells using CRISPR/Cas9 technology, based on the expertise of Team 11 at CRCI²NA. The study will include 60 patients over a 9-year enrollment period. Each participant will be followed for 5 years, resulting in a total study duration of 14 years.
7 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anne LOK, MD, PhD principal investigator
Hospital of Nantes
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Lymphocytic Leukemia and BTK Degraders, run by Nantes University Hospital at 14 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ANNE LOK, Dr (02.40.08.42.11, anne.lok@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of resistance mechanisms to CLL patients candidates or exposed to BTKd. (time frame: Up to 5 years after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.