- ICH GCP
- US-Register für klinische Studien
- Klinische Studie 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).
Studienübersicht
Status
Detaillierte Beschreibung
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
Studientyp
Einschreibung (Tatsächlich)
Kontakte und Standorte
Studienorte
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Marseille, Frankreich, 13000
- Institut Paoli Calmette
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Montpellier, Frankreich, 34000
- Montpellier University Hospital
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Brittanny
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Rennes, Brittanny, Frankreich, 35000
- Rennes EFS
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Rennes, Brittanny, Frankreich, 35000
- Rennes University Hospital
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
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Gesunde Freiwillige
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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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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
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
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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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Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Thierry Fest, MD, Rennes University Hospital
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Hautkrankheiten
- Erkrankungen der Atemwege
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Lymphatische Erkrankungen
- Immunproliferative Erkrankungen
- Lymphom, Non-Hodgkin
- Lungenkrankheit
- Neubildungen nach Standort
- Brusterkrankungen
- Neubildungen der Atemwege
- Thoraxneoplasmen
- Karzinom, bronchogen
- Bronchiale Neubildungen
- Lungentumoren
- Lymphom
- Lymphom, B-Zell
- Lymphom, große B-Zelle, diffus
- Neoplasien der Brust
- Karzinom, nicht-kleinzellige Lunge
- Hodgkin-Krankheit
Andere Studien-ID-Nummern
- 2011-A01163-38
- B111181-40 (Andere Kennung: AFSSAPS)
- 11/32-821 (Andere Kennung: CPP OUest V)
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