BMS_PD-L1_onco : Assessment of the PD-L1 Protein as a Biomarker in Oncology and Hematology
Conditions
Diffuse Large B-cell Lymphoma - Hodgkin Lymphoma - Metastatic Breast Cancer. - Non-small Cell Lung Cancer
Conditions: official terms
Carcinoma, Non-Small-Cell Lung - Hodgkin Disease - Lymphoma - Lymphoma, B-Cell - Lymphoma, Large B-Cell, Diffuse
Conditions: Keywords
diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, metastatic breast cancer., non-small cell lung cancer
Study Type
Observational
Study Phase
N/A
Study Design
Observational Model: Case-Crossover, Time Perspective: Prospective
Overall Status
Recruiting
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).
Detailed Description
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
Criteria for eligibility
Healthy Volunteers: Accepts Healthy Volunteers
Maximum Age: 75 Years
Minimum Age: 18 Years
Gender: Both
Criteria: 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 volunteers :

- Inclusion criteria for blood donation according to the Etablissement Français du Sang (EFS) criteria

Exclusion Criteria:

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
Locations
Rennes EFS
Rennes, Brittanny, France
Status: Recruiting
Contact: Gilbert Semana, MD
Rennes University Hospital
Rennes, Brittanny, France
Status: Recruiting
Contact: Thierry Fest, MD - thierry.fest@chu-rennes.fr
Institut Paoli Calmette
Marseille, France
Status: Recruiting
Contact: Florence Broussais, MD
Montpellier University Hospital
Montpellier, France
Status: Recruiting
Contact: Guillaume Cartron, MD
Start Date
June 2012
Completion Date
June 2017
Sponsors
Rennes University Hospital
Source
Rennes University Hospital
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page