CompletedNot Applicable

BMS_PD-L1_onco : Assessment of the PD-L1 Protein as a Biomarker in Oncology and Hematology

France105 participantsStarted 2012-06-07

Plain-language summary

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).

Who can participate

Age range18 Years – 75 Years

SexALL

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Inclusion Criteria: 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 volunte…

What they're measuring

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

Timeframe: 4 years

Trial details

NCT IDNCT01660776

SponsorRennes University Hospital

Sponsor typeOTHER

Study typeOBSERVATIONAL

Primary completion2017-10-02