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

NCT ID: NCT01660776

Last Updated: 2019-11-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 105 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-06-07
• Study Completion Date: 2019-10-02

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).

Detailed Description

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

Conditions

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

Study Design

• Observational Model Type: CASE_CROSSOVER
• Study Time Perspective: PROSPECTIVE

Study Groups

DLBCL (diffuse large B-cell lymphoma)

DLBCL (diffuse large B-cell lymphoma)

No interventions assigned to this group

Hodgkin's lymphoma

Hodgkin's lymphoma

No interventions assigned to this group

metastatic breast cancer

metastatic breast cancer or with lymph node involvement

No interventions assigned to this group

immune thrombocytopenia (ITP)

immune thrombocytopenia (ITP)

No interventions assigned to this group

healthy volunteers

healthy volunteers

No interventions assigned to this group

non-small cell lung cancer

non-small cell lung cancer

No interventions assigned to this group

Eligibility Criteria

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

• 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

• 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

• 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

• Central aetiology of the thrombocytopenia

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

National Research Agency, France

OTHER

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thierry Fest, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Locations

Rennes EFS

Rennes, Brittanny, France

Rennes University Hospital

Rennes, Brittanny, France

Institut Paoli Calmette

Marseille, , France

Montpellier University Hospital

Montpellier, , France

Countries

France

Other Identifiers

B111181-40

Identifier Type: OTHER

Identifier Source: secondary_id

11/32-821

Identifier Type: OTHER

Identifier Source: secondary_id

2011-A01163-38

Identifier Type: -

Identifier Source: org_study_id