La Trogocytose Est-elle un Marqueur prédictif de la réponse Aux Cellules CAR-T Dans Les Lymphomes Diffus à Grandes Cellules B ?
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 85
- 试验地点
- 4
- 主要终点
- Identification of a phenotypic "signature" of trogocytosis predictive of failure to achieve a complete metabolic response for patients with diffuse large B-cell lymphoma.
研究概览
简要总结
CAR-T cell therapy has improved survival in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL R/R). However, only 65% of patients achieve a complete metabolic response after this treatment. To date, there is no predictive test for therapeutic response after injection of CAR-T cells. Recent studies have shown that the level of trogocytosis by immune cells correlates with the persistence of tumor cells in patients with hematological malignancies. Our main objective is to identify a phenotypic "signature" of trogocytosis predictive of therapeutic response 6 months after injection of CAR-T cells for DLBCL.
详细描述
The therapeutic use of CAR-T cells (Chimeric Antigen Receptor T-cells) has significantly improved the survival of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, only 65% of patients achieve metabolic complete response after this treatment, and one year after CAR-T cells infusion, between 50 and 60% of patients have relapsed or died. Injection of CAR-T cells can also be responsible for serious immunologic and hematologic adverse events. To date, there is no predictive test for the therapeutic response or toxicity following injection of CAR-T cells.
Trogocytosis is a physiological mechanism by which an effector immune cell integrates fragments of the membrane of target cells into its membrane. These aberrant membrane markers can directly modify the functions of the cell that has acquired them. Although the physiological role of trogocytosis remains debated, recent studies have shown that the level of trogocytosis in immune effector cells is correlated with persistent tumor cells in patients with hematological malignancies.
Our main hypothesis is that, in DLBCL, the level of early trogocytosis, assessed by the aberrant expression of tumor markers on the surface of CAR-T cells and other immune effector cells between D0 and D30 after CAR-T cells infusion, correlates with therapeutic response at M6 and/or the occurrence of immunological or severe hematological CAR-T cells side-effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For patients
- •Patient who has given free and informed consent in writing for inclusion in the non-interventional CART-BANK protocol, and orally for the CARTROG protocol,
- •Patients over 18 years of age at the time of inclusion,
- •Diagnosis of LDGCB,
- •Decision to treat with anti-CD19 CAR-T cells,
- •Patient affiliated to or benefiting from a social security scheme.
- •For healthy volunteers:
- •Given free and informed oral consent for inclusion in the CARTROG protocol,
- •Donor between 18 and 70 years of age at the time of inclusion,
- •No history of solid cancer or hematological malignancy,
- •No known chronic pathology (e.g. hypertension, diabetes, etc.) and no daily treatment,
- •No surgical treatment within the last 6 months.
排除标准
- •Patients who do not meet all the inclusion criteria,
- •Pregnant or breast-feeding patient,
- •Patient unable to follow the procedures and/or frequency of visits planned in the trial, for psychological, family, social or geographical reasons,
- •Patient unable to consent freely to inclusion, under guardianship, curatorship or safeguard of justice.
研究组 & 干预措施
Patients
Blood sample for Flow cytometry analysis
干预措施: Flow cytometry analysis to determine the level of trogocytosis by effector immune cells in patients (Other)
healthy volunteer donor
Blood sample for Flow cytometry analysis
干预措施: Flow cytometry analysis to determine the level of trogocytosis by effector immune cells in volunteers (Other)
结局指标
主要结局
Identification of a phenotypic "signature" of trogocytosis predictive of failure to achieve a complete metabolic response for patients with diffuse large B-cell lymphoma.
时间窗: During 6 months after CAR-T cells injection
Using flow cytometry to determine the level of trogocytosis, the phenotypic "signature" of trogocytosis will be assessed by the AUC : area under the ROC (Receiver operating characteristic) curve; established on circulating CAR-T cells, T lymphocytes and NK cells of patients, and defined as: the percentage of cells aberrantly expressing different tumor antigens normally expressed on lymphoma cells (CD19, CD20, etc.) at the different analysis times and/or the median florescence intensity (MFI) of the expression of these markers at the different analysis times and/or the evolution of these percentages and the MFI between 2 analysis times. Failure to obtain a complete metabolic response will be defined by: the absence of a complete metabolic response on the PET scans of D30, D90 and M6 in the absence of implementation of a new therapeutic line; or by the absence of complete metabolic response on all PET scans carried out before the implementation of a new therapeutic line.
次要结局
- Identification of a phenotypic "signature" of trogocytosis predictive of the occurrence of grade II or more immunological adverse events(During 60 days after CAR-T cells injection)
- Determination of the trogocytosis level of normal lymphocytes and NK cells in healthy subjects(At enrollment)
- Identification of a phenotypic "signature" of trogocytosis predictive of the occurrence of serious hematological side effects.(Between Day 30 and 6 months after CAR-T cells injection)