Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

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

5 de novembro de 2019 atualizado por: 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).

Visão geral do estudo

Status

Concluído

Condições

Descrição detalhada

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 de estudo

Observacional

Inscrição (Real)

105

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 75 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Sim

Gêneros Elegíveis para o Estudo

Tudo

Método de amostragem

Amostra de Probabilidade

População do estudo

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

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Coortes e Intervenções

Grupo / Coorte
voluntários saudáveis
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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
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
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
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
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Rennes University Hospital

Colaboradores

Roche Pharma AG
National Research Agency, France

Investigadores

  • Investigador principal: Thierry Fest, MD, Rennes University hospital

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

7 de junho de 2012

Conclusão Primária (Real)

2 de outubro de 2017

Conclusão do estudo (Real)

2 de outubro de 2019

Datas de inscrição no estudo

Enviado pela primeira vez

31 de julho de 2012

Enviado pela primeira vez que atendeu aos critérios de CQ

6 de agosto de 2012

Primeira postagem (Estimativa)

9 de agosto de 2012

Atualizações de registro de estudo

Última Atualização Postada (Real)

6 de novembro de 2019

Última atualização enviada que atendeu aos critérios de controle de qualidade

5 de novembro de 2019

Última verificação

1 de novembro de 2019

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Ensaios clínicos em Linfoma de Hodgkin

Pesquisar ensaios semelhantes

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

CROs by country

CROs in Uzbekistan

Condições

Doenças Raras

Intervenções de drogas

Suplementos Alimentares

Patrocinador / Colaboradores

Localizações

3
Se inscrever