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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 de noviembre de 2019 actualizado 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).

Descripción general del estudio

Estado

Terminado

Condiciones

Descripción detallada

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 estudio

De observación

Inscripción (Actual)

105

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • 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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 75 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

Sí

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra de probabilidad

Población de estudio

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

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

Cohortes e Intervenciones

Grupo / Cohorte
voluntarios sanos
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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
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
Periodo de tiempo: 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 resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Rennes University Hospital

Colaboradores

Roche Pharma AG
National Research Agency, France

Investigadores

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

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

7 de junio de 2012

Finalización primaria (Actual)

2 de octubre de 2017

Finalización del estudio (Actual)

2 de octubre de 2019

Fechas de registro del estudio

Enviado por primera vez

31 de julio de 2012

Primero enviado que cumplió con los criterios de control de calidad

6 de agosto de 2012

Publicado por primera vez (Estimar)

9 de agosto de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

6 de noviembre de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

5 de noviembre de 2019

Última verificación

1 de noviembre de 2019

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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