BMS_PD-L1_onco : Assessment of the PD-L1 Protein as a Biomarker in Oncology and Hematology
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 105
- 试验地点
- 4
- 主要终点
- Description of one or several blood cell types producing soluble PD-L1 in DLBCL, metastatic breast cancer, Hodgkin's lymphoma and non-small cell lung cancer
研究概览
简要总结
Diffuse large B-cell lymphomas (DLBCLs) represent 25 to 30% of adult non-Hodgkin lymphomas in western countries. DLBCLs are aggressive cancer but potentially curable with multi-agent chemotherapy. Whereas R-CHOP regimen has led to a marked improvement in survival, this disease remains a biologically heterogeneous entity. New therapeutic strategies are required including identification of patients' subgroups with different prognostic.
This project is based on BMS_LyTrans and Goelams 075 clinical trial. A study of whole blood transcriptome in 75 DLBCL patients and in 87 controls showed that PD-L1 (CD274) gene was overexpressed in DLBCL patients. Preliminary results demonstrated that PD-L1 is detected in plasma of DLBCL patients with a significantly higher concentration than in controls. This protein was selected as a potential biomarker because of its established role in anti-tumoral immunity. Interaction between PD-L1 and its receptor PD-1 is known to inhibit activation of immune responses by inducing T-lymphocytes anergy and/or apoptosis. Moreover, a direct involvement of PD-L1 in the protection of cancer cells from lysis by activated T lymphocytes has been demonstrated. PD-L1 expression has been described in several solid tumours, including ovary cancer, breast cancer, colon cancer, renal cell carcinoma, non-small cell lung carcinoma and in hematological malignancies such as T-NHL, MM and Hodgkin's lymphoma. Furthermore the expression of PD-L1 by tumour cells is associated with poor prognosis. The blockade of PD-L1/PD-1 axis may represent a novel therapeutic approach in aggressive cancers. These first results incite to identify the cells releasing soluble PD-L1 and to investigate its role in the anti-tumoral immunity in DLBCL patients.
The aim of this study is to identify cells producing soluble PD-L1 in DLBCL patients at diagnosis in comparison to others tumours known to express PD-L1 (metastatic breast cancer, Hodgkin's lymphoma, non-small cell lung cancer).
详细描述
Secondary purposes are :
- To confirm the presence of plasma soluble form of PD-L1 in others malignancies
- To study surface expression of PD-L1 on circulating tumour cells with multiparameter fow cytometry and Veridex® technology in DLBCL and metastatic breast cancer patients
- To study surface expression of PD-L1 on circulating endothelial cells in DLBCL, Hodgkin lymphoma and metastatic breast cancer patients (subpart ended in late 2012)
- To study surface expression of PD-L1 on different types of leukocytes (monocytes, B and T lymphocytes)
- To separate circulating tumour cells expressing PD-L1 by immunomagnetic or Cell-sorting method
- To develop ELISPOT technique to study the release of soluble PD-L1 in culture supernatants of selected cells (subpart ended mid 2013)
- to evaluate the correlation between the expression of PD-L1 in the plasma and *) the expression of PD-L1 in the tumor, **) the expression of PD-L1 and other molecules in the bronchoalveolar liquid (whenever available from routine) in non-small cell lung cancer
- to evaluate the response to treatment according to plasma PD-L1 expression in non-small cell lung cancer
- to evaluate the susceptibility to develop a disease according to the single nucleotide polymorphisms of the PD-L1 gene in DLBCL and non-small cell lung cancer
- Constitution of the different cohorts and collection of samples Main cohort : de novo DLBCL at diagnosis Secondary cohorts: Hodgkin's lymphoma, metastatic breast cancer, non small cell lung cancer Control cohorts : healthy volunteers (blood donors), patients with immune thrombocytopenia (ITP)
- Quantification of plasma soluble PD-L1 in the different cohorts
研究设计
- 研究类型
- Observational
- 观察模型
- Case Crossover
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General inclusion criteria :
- •Age ≥ 18 years and ≤ 75 years,
- •Life expectancy more than 4 months
- •Signed informed consent obtained
- •Social security affiliation is mandatory
- •Non previously treated (even by corticotherapy),
- •HIV negative, HBs negative, HCV negative
- •Inclusion criteria for DLBCL patients :
- •A biopsy proven diagnosis of de novo DLBCL according to the current WHO criteria,
- •Immunohistochemistry for GCB/nonGC classification according to Hans' algorithm
- •Patients with advanced-stage disease defined as Ann Arbor stages III or IV, or stages I or II with bulky disease (>7cm)
- •Inclusion criteria for non-small cell lung cancer patients :
- •A biopsy proven diagnosis of de novo non-small cell lung cancer (all stages) according to the current WHO criteria
- •Inclusion criteria for Hodgkin's lymphoma patients :
- •A biopsy proven diagnosis of Hodgkin's lymphoma according to the current WHO criteria
- •Inclusion criteria for metastatic breast cancer or with lymph node involvement :
- •A biopsy proven diagnosis infiltrating lobular or ductal breast carcinoma
- •with lymph node involvement or metastasis
- •Inclusion criteria for patients with immune thrombocytopenia (ITP) :
- •Primary ITP was defined by the IWG as a platelet count less than 100 G/L in the absence of other causes or disorders that may be associated with thrombocytopenia.
- •Bone marrow examination excluding a central aetiology of thrombocytopenia
- •Inclusion criteria for healthy volunteers :
- •Inclusion criteria for blood donation according to the Etablissement Français du Sang (EFS) criteria
排除标准
- •General non-inclusion criteria :
- •Age < 18 years et > 75 years,
- •Pregnant women,
- •Person legally involved in a case
- •No social security affiliation
- •Signed informed consent not obtained,
- •Preliminary treatment (even corticoid treatment).
- •HIV positive, HBs positive, HCV positive
- •Non-inclusion criteria for DLBCL patients :
- •Lymphoma other than DLBCL,
- •Transformation of a low grade lymphoma to a high grade lymphoma (DLBCL),
- •Extranodal marginal zone lymphoma of MALT lymphoma,
- •Post-transplant lymphoproliferative disorders,
- •Lymphoblastic lymphoma,
- •Burkitt's lymphoma,
- •Carcinoma or history of carcinoma except in situ cervical carcinoma.
- •Non-inclusion criteria for non-small cell lung cancer patients : None
- •Non-inclusion criteria for Hodgkin patients :
- •Non Hodgkin's lymphoma
- •Non-inclusion criteria for metastatic breast cancer or with lymph node involvement :
- •Carcinoma other than infiltrating lobular or ductal breast carcinoma
- •Chemotherapy in 30 days preceding the inclusion
- •Hormonotherapy in 7 days preceding the inclusion
- •Carcinoma or history of carcinoma except in situ cervical carcinoma.
- •Hemoglobin level < 10g/dl
- •Non-inclusion criteria for patients with immune thrombocytopenia (ITP) :
- •Central aetiology of the thrombocytopenia
- •Non-inclusion criteria for healthy volunteers :
- •Exclusion criteria for blood donation according to the Etablissement Français du Sang (EFS) criteria
结局指标
主要结局
Description of one or several blood cell types producing soluble PD-L1 in DLBCL, metastatic breast cancer, Hodgkin's lymphoma and non-small cell lung cancer
时间窗: 4 years
Description of one or several blood cell types producing soluble PD-L1 in DLBCL, metastatic breast cancer, Hodgkin's lymphoma and non-small cell lung cancer
次要结局
- Analysis of PD-L1 membrane protein expression on circulating tumor cells by multiparameter flow cytometry and Veridex® in DLBCL and metastatic breast cancer, and bone marrow tumor cells by flow cytometry in DLBCL(4 years)
- Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts(4 years)
- Development of an ELISPOT technique to detect soluble PD-L1 in the supernatants of sorted primary cells (subpart ended mid 2013)(4 years)
- Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer(4 years)
- Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1(4 years)
- Analysis of PD-L1 membrane protein expression on circulating endothelial cells with the Veridex® technology in DLBCL, Hodgkin's lymphoma and metastatic breast cancer (subpart ended in late 2012)(4 years)
- Correlation between the PD-L1 expression *) in the plasma, **) in the tumor and ***) in the bronchoalveolar liquid in non-small cell lung cancer(4 years)
- Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer(4 years)