Determinants of the Response to BTK Degraders (BTKd) in Double Refractory CLL

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-10-09

Study Completion Date

2039-09-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The aim of the REBELLE cohort - bio-collection is to collect samples from patients with Chronic Lymphocytic Leukemia (CLL), to facilitate access for the National Institute of Health and Medical Research (INSERM) to patients with double-refractory CLL. 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. These samples will first be sent to the Filothèque for temporary storage, and will then be transferred to CRCI²NA (Nantes - Angers Cancer and Immunology Research Center) for analysis with the aim of studying the mechanisms of resistance and response to BTK degraders (BTKd).

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

A Phase IB Study Of The BTKi CC-292 Combined With Lenalidomide In Adults Patients With Relapsed/Refractory B-Cell Lymphoma

NCT01766583

Relapsed/Refractory B-cell Lymphoma

COMPLETED PHASE1

An Observational Study of MabThera/Rituxan (Rituximab) in Patients With Relapsing or Refractory Chronic Lymphocytic Leukemia

NCT01488162

Lymphocytic Leukemia, Chronic

COMPLETED

Study of Nivolumab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) That Have Either Failed or Are Not Eligible for Autologous Stem Cell Transplant (CheckMate 139)

NCT02038933

Lymphoma. Non-Hodgkin

COMPLETED PHASE2

Tissue Collection for Biomarkers Determining Resistance to Ibrutinib

NCT02267590

Mantle Cell Lymphoma Chronic Lymphocytic Leukaemia

UNKNOWN

BR in Patients With CLL With Comorbidities and/or Renal Dysfunction

NCT01832922

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Chronic Lymphocytic Leukemia (CLL) is a malignant B-cell disorder characterized by the accumulation of CD19+CD5+ lymphocytes in the bone marrow, lymph nodes, spleen, and peripheral blood. It has an incidence of approximately 4.2 cases per 100,000 people annually, with a median diagnosis age of 72 years. CLL exhibits marked biological and clinical heterogeneity, influenced by prognostic factors such as Immunoglobulin Heavy Chain Variable Region (IGHV) mutation status, TP53 alterations, and complex karyotypes. The disease is typically indolent, and treatment initiation follows criteria established by the International Workshop on CLL (IWCLL). Symptoms, when present, include lymphadenopathy, cytopenias, and infections. About one-third of patients require treatment at diagnosis, another third within ten years, and the remaining third may never need therapy. Although incurable, CLL generally has favorable progression-free and overall survival rates.Historically, chemotherapy was the main treatment, but the advent of targeted oral therapies-particularly Bruton tyrosine kinase inhibitors (BTKi) and BCL-2 inhibitors (BCL-2i)-has significantly improved patient outcomes. BTKi block the BTK enzyme critical for B-cell receptor signaling, thereby inhibiting malignant B-cell proliferation and survival. BCL-2 inhibitors induce apoptosis by binding to the anti-apoptotic BCL-2 protein, which CLL cells often overexpress. Combined use of these agents with monoclonal antibodies has become standard care. Despite these advances, approximately 20% of patients develop resistance to chemotherapy or targeted therapies. A rare but clinically significant subgroup, termed double refractory, fails to respond to both BTKi and BCL-2i and has a poor prognosis. Defining resistance includes clinical progression on therapy and biological markers such as mutations associated with drug resistance. Resistance to BTKi arises from compensatory signaling pathways or mutations within BTK, whereas resistance to BCL-2 inhibitors is typically identified when patients relapse during or soon after treatment.. To overcome resistance to BTKi, novel BTK degraders (BTKd) are under development. Unlike BTKi, these heterobifunctional molecules induce proteasomal degradation of the BTK protein via ubiquitination, showing promising preclinical efficacy. However, limited clinical data exist on BTKd, and researchers still need to carry out a full evaluation of their effectiveness against other resistance mechanisms and in combination with current immunotherapies. To gain a better understanding of resistance and response to BTKd, establishing a dedicated cohort and biobank of samples from double-refractory CLL patients is essential. Collaborating with research teams specialized in hematologic malignancies, such as the CRCI²NA group, and leveraging existing frameworks like the FILO/LYSA ( French Innovative Leukemia Organization/Network for clinical lymphomas and CLL/WM research) networks, will enable comprehensive translational studies. This initiative aims to address the urgent need for novel therapeutic strategies in this challenging patient population.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Lymphocytic Leukemia Refractory Chronic Lymphocytic Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

double-refractory CLL patients

Collection of additional samples of blood and bone marrow or residual lymph node biopsy at the time of inclusion (for diagnosis or relapse) and relapse.

Non-Interventional Sample Collection and Analysis

Intervention Type OTHER

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patient with confirmed double refractory CLL to both BTKi and BCL-2i, defined as:

* Any patient who has received both a BTKi and a BCL-2i, regardless of treatment regimen, and has shown clinical progression either during treatment with both BTKi and BCL-2i, or within 36 months after stopping BCL-2i.
* Any patient identified with known biological resistance mutations to BTKi or BCL-2i, regardless of clinical progression.
* Patient who has provided informed consent to participate in the study.
* Patient covered by a social security health insurance plan