このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

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

2019年11月5日 更新者：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).

調査の概要

状態

完了

条件

詳細な説明

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

研究の種類

観察的

入学 (実際)

105

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • フランス
      • Marseille、フランス、13000
        • Institut Paoli Calmette
      • Montpellier、フランス、34000
        • Montpellier University Hospital
    • Brittanny
      • Rennes、Brittanny、フランス、35000
        • Rennes EFS
      • Rennes、Brittanny、フランス、35000
        • Rennes University Hospital

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～75年 (大人、高齢者)

健康ボランティアの受け入れ

はい

受講資格のある性別

全て

サンプリング方法

確率サンプル

調査対象母集団

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

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

コホートと介入

グループ/コホート
健康なボランティア
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

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
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
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
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
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Rennes University Hospital

協力者

Roche Pharma AG
National Research Agency, France

捜査官

  • 主任研究者：Thierry Fest, MD、Rennes University Hospital

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2012年6月7日

一次修了 (実際)

2017年10月2日

研究の完了 (実際)

2019年10月2日

試験登録日

最初に提出

2012年7月31日

QC基準を満たした最初の提出物

2012年8月6日

最初の投稿 (見積もり)

2012年8月9日

学習記録の更新

投稿された最後の更新 (実際)

2019年11月6日

QC基準を満たした最後の更新が送信されました

2019年11月5日

最終確認日

2019年11月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • 2011-A01163-38
  • B111181-40 (その他の識別子：AFSSAPS)
  • 11/32-821 (その他の識別子：CPP OUest V)

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

購読する