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

5 novembre 2019 aggiornato da: Rennes University Hospital

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).

Panoramica dello studio

Stato

Completato

Condizioni

Descrizione dettagliata

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

Tipo di studio

Osservativo

Iscrizione (Effettivo)

105

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Francia
      • Marseille, Francia, 13000
        • Institut Paoli Calmette
      • Montpellier, Francia, 34000
        • Montpellier University Hospital
    • Brittanny
      • Rennes, Brittanny, Francia, 35000
        • Rennes EFS
      • Rennes, Brittanny, Francia, 35000
        • Rennes University Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione di probabilità

Popolazione di studio

Number of DLBCL patients : 40 Number of non-small cell lung cancer patients : 100 Number of Hodgkin patients : 20 Number of metastatic breast cancer patients : 20 Number of healthy volunteers : 140 Number of patients with immune thrombocytopenia (ITP) : 5

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Coorti e interventi

Gruppo / Coorte
volontari sani
DLBCL (diffuse large B-cell lymphoma)
Hodgkin's lymphoma
metastatic breast cancer
metastatic breast cancer or with lymph node involvement
immune thrombocytopenia (ITP)
non-small cell lung cancer

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
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
Lasso di tempo: 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
4 years

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
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
Lasso di tempo: 4 years
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 circulating endothelial cells with the Veridex® technology in DLBCL, Hodgkin's lymphoma and metastatic breast cancer (subpart ended in late 2012)
Lasso di tempo: 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
Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts
Lasso di tempo: 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)
Lasso di tempo: 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 techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
Lasso di tempo: 4 years
Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
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
Lasso di tempo: 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
Lasso di tempo: 4 years
Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer
4 years
Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Rennes University Hospital

Collaboratori

Roche Pharma AG
National Research Agency, France

Investigatori

  • Investigatore principale: Thierry Fest, MD, Rennes University Hospital

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

7 giugno 2012

Completamento primario (Effettivo)

2 ottobre 2017

Completamento dello studio (Effettivo)

2 ottobre 2019

Date di iscrizione allo studio

Primo inviato

31 luglio 2012

Primo inviato che soddisfa i criteri di controllo qualità

6 agosto 2012

Primo Inserito (Stima)

9 agosto 2012

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

6 novembre 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

5 novembre 2019

Ultimo verificato

1 novembre 2019

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2011-A01163-38
  • B111181-40 (Altro identificatore: AFSSAPS)
  • 11/32-821 (Altro identificatore: CPP OUest V)

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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