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

NCT01660776 | Completed

• 3 other identifiers: 2011-A01163-38B111181-4011/32-821
• Study Type: observational
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Diffuse Large B-cell Lymphoma; Hodgkin Lymphoma; Metastatic Breastcancer; Non-small Cell Lung Cancer

Keywords

diffuse large B-cell lymphoma (DLBCL); Hodgkin lymphoma; metastatic breast cancer.; non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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

Secondary Outcomes (8)

• 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)

  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)

  4 years

• Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1

  4 years

Study Arms (6)

DLBCL (diffuse large B-cell lymphoma)

DLBCL (diffuse large B-cell lymphoma)

Hodgkin's lymphoma

Hodgkin's lymphoma

metastatic breast cancer

metastatic breast cancer or with lymph node involvement

immune thrombocytopenia (ITP)

immune thrombocytopenia (ITP)

healthy volunteers

healthy volunteers

non-small cell lung cancer

non-small cell lung cancer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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
• 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)
• A biopsy proven diagnosis of de novo non-small cell lung cancer (all stages) according to the current WHO criteria
• A biopsy proven diagnosis of Hodgkin's lymphoma according to the current WHO criteria
• A biopsy proven diagnosis infiltrating lobular or ductal breast carcinoma
• with lymph node involvement or metastasis
• 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

You may not qualify if:

• 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
• 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 Hodgkin's lymphoma

Sponsors & Collaborators

• Rennes University Hospital: lead
• Roche Pharma AG: collaborator
• National Research Agency, France: collaborator

Study Sites (4)

Rennes EFS

Rennes, Brittanny, 35000, France

Location

Rennes University Hospital

Rennes, Brittanny, 35000, France

Location

Institut Paoli Calmette

Marseille, 13000, France

Location

Montpellier University Hospital

Montpellier, 34000, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biomedical research on total blood at diagnosis.

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Hodgkin Disease; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Thierry Fest, MD

  Rennes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2012
• First Posted: August 9, 2012
• Study Start: June 7, 2012
• Primary Completion: October 2, 2017
• Study Completion: October 2, 2019
• Last Updated: November 6, 2019

Record last verified: 2019-11

Locations

FR (4)