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- Klinische proef NCT01660776
BMS_PD-L1_onco : Assessment of the PD-L1 Protein as a Biomarker in Oncology and Hematology (BMS_PD-L1)
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).
Studie Overzicht
Toestand
Gedetailleerde beschrijving
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
Studietype
Inschrijving (Werkelijk)
Contacten en locaties
Studie Locaties
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Marseille, Frankrijk, 13000
- Institut Paoli Calmette
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Montpellier, Frankrijk, 34000
- Montpellier University Hospital
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Brittanny
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Rennes, Brittanny, Frankrijk, 35000
- Rennes EFS
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Rennes, Brittanny, Frankrijk, 35000
- Rennes University Hospital
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Bemonsteringsmethode
Studie Bevolking
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
Cohorten en interventies
Groep / Cohort |
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gezonde vrijwilligers
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DLBCL (diffuse large B-cell lymphoma)
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Hodgkin's lymphoma
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metastatic breast cancer
metastatic breast cancer or with lymph node involvement
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immune thrombocytopenia (ITP)
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non-small cell lung cancer
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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
Tijdsspanne: 4 years
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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
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4 years
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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
Tijdsspanne: 4 years
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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
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4 years
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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)
Tijdsspanne: 4 years
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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)
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4 years
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Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts
Tijdsspanne: 4 years
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Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts
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4 years
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Development of an ELISPOT technique to detect soluble PD-L1 in the supernatants of sorted primary cells (subpart ended mid 2013)
Tijdsspanne: 4 years
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Development of an ELISPOT technique to detect soluble PD-L1 in the supernatants of sorted primary cells (subpart ended mid 2013)
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4 years
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Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
Tijdsspanne: 4 years
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Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
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4 years
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Correlation between the PD-L1 expression *) in the plasma, **) in the tumor and ***) in the bronchoalveolar liquid in non-small cell lung cancer
Tijdsspanne: 4 years
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Correlation between the PD-L1 expression *) in the plasma, **) in the tumor and ***) in the bronchoalveolar liquid in non-small cell lung cancer
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4 years
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Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer
Tijdsspanne: 4 years
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Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer
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4 years
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Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer
Tijdsspanne: 4 years
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Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer
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4 years
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Thierry Fest, MD, Rennes University Hospital
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Huidziektes
- Ziekten van de luchtwegen
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Lymfatische ziekten
- Immunoproliferatieve aandoeningen
- Lymfoom, non-Hodgkin
- Longziekten
- Neoplasmata per site
- Borst ziekten
- Neoplasmata van de luchtwegen
- Thoracale neoplasmata
- Carcinoom, bronchogeen
- Bronchiale neoplasmata
- Longneoplasmata
- Lymfoom
- Lymfoom, B-cel
- Lymfoom, grote B-cel, diffuus
- Borstneoplasmata
- Carcinoom, niet-kleincellige long
- Ziekte van Hodgkin
Andere studie-ID-nummers
- 2011-A01163-38
- B111181-40 (Andere identificatie: AFSSAPS)
- 11/32-821 (Andere identificatie: CPP OUest V)
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