Determinants of the Response to BTK Degraders (BTKd) in Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 15
- 主要终点
- Characterization of resistance mechanisms to CLL patients candidates or exposed to BTKd.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Minor patients.
- •Adults under guardianship.
- •Protected persons.
研究组 & 干预措施
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.
干预措施: Non-Interventional Sample Collection and Analysis (Other)
结局指标
主要结局
Characterization of resistance mechanisms to CLL patients candidates or exposed to BTKd.
时间窗: 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.
Characterization of resistance mechanisms to BTK degraders in double-refractory CLL patients
时间窗: Up to 5 years after inclusion
The primary outcome is the in-depth characterization of tumor cells and their microenvironment in double-refractory CLL patients. 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.
次要结局
- Generation of knockout cell lines for genes of interest(Up to 5 years after inclusion)
- Development of preclinical ex vivo culture models(Up to 5 years after inclusion)
- Genomic data analysis to identify resistance-related genes(Up to 5 years after inclusion)
- Genetic modification of primary CLL cells(Up to 5 years after inclusion)
- Identification of new tumor targets(Up to 5 years after inclusion)
- Pharmacological targeting of novel candidate molecules(Up to 5 years after inclusion)
- Generation of drug-resistant cell lines and comparative RNA sequencing(Up to 5 years after inclusion)
- Reconstruction of the tumor microenvironment using co-culture systems(Up to 5 years after inclusion)