Diffuse Large B-cell LymphomaBMS_PD-L1NCT01660776
BMS_PD-L1_onco : Assessment of the PD-L1 Protein as a Biomarker in Oncology and Hematology
An observational study of Diffuse Large B-cell Lymphoma and Hodgkin Lymphoma, run by Rennes University Hospital at 4 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, Hodgkin Lymphoma, Metastatic Breastcancer
- How many people
- 105 participants
- Where
- 4 sitesFrance
- Study dates
- 7 Jun 2012to 2 Oct 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- 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),
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- 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)
- 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
- 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 blood donation according to the Etablissement Français du Sang (EFS) criteria
Who cannot join
- 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,
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- 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
Trial locations and contacts
4 sites in 1 country.
France4 sites
Institut Paoli Calmette
Marseille, 13000
Montpellier University Hospital
Montpellier, 34000
Rennes EFS
Rennes, Brittanny, 35000
Rennes University Hospital
Rennes, Brittanny, 35000
About this study
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).
Read the 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
- Keywords
- diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, metastatic breast cancer., non-small cell lung cancer
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Hodgkin Disease, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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
Measured: 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)
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)
Measured: 4 years
Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts
Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts
Measured: 4 years
Development of an ELISPOT technique to detect soluble PD-L1 in the supernatants of sorted primary cells (subpart ended mid 2013)
Development of an ELISPOT technique to detect soluble PD-L1 in the supernatants of sorted primary cells (subpart ended mid 2013)
Measured: 4 years
Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
Measured: 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
Correlation between the PD-L1 expression *) in the plasma, ) in the tumor and *) in the bronchoalveolar liquid in non-small cell lung cancer
Measured: 4 years
Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer
Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer
Measured: 4 years
Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer
Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study start7 Jun 2012
- Primary completion2 Oct 2017
- Study completion2 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG, National Research Agency, France
- Responsible party
- Sponsor
- Investigators
- Thierry Fest, MD, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01660776
- Sponsor's protocol ID
- 2011-A01163-38
- Other IDs
- B111181-40, 11/32-821
- Acronym
- BMS_PD-L1
- Status last verified
- Nov 2019
- First submitted
- 31 Jul 2012
- Last updated
- 6 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BMS_PD-L1_onco : Assessment of the PD-L1 Protein as a Biomarker in Oncology and Hematology
- ClinicalTrials.gov ID
- NCT01660776
- Acronym / sponsor ID
- BMS_PD-L1 / 2011-A01163-38
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Collaborators
- Roche Pharma AG, National Research Agency, France
- Study start
- 7 Jun 2012 (actual)
- Primary completion
- 2 Oct 2017 (actual)
- Study completion
- 2 Oct 2019 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (20 listed)
- 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),
Key exclusion criteria (29 listed)
- Age < 18 years et > 75 years,
- Pregnant women,
- Person legally involved in a case
- No social security affiliation
- Signed informed consent not obtained,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Time frame: 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
8 secondary outcomes
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
Time frame: 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)
Time frame: 4 years
Analysis of PD-L1 membrane protein expression on monocytes, B and T lymphocytes in all cohorts
Time frame: 4 years
Development of an ELISPOT technique to detect soluble PD-L1 in the supernatants of sorted primary cells (subpart ended mid 2013)
Time frame: 4 years
Evaluation of the techniques (by immunomagnetic or cell-sorting) used to separate circulating tumor cells expressing PD-L1
Time frame: 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
Time frame: 4 years
Evaluation of the response to treatment according to soluble PD-L1 expression in non-small cell lung cancer
Time frame: 4 years
Evaluation of the susceptibility to develop a disease according to PD-L1 gene SNP in DLBCL and non-small cell lung cancer
Time frame: 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thierry Fest, MD principal investigator
Rennes University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diffuse Large B-cell Lymphoma and Hodgkin Lymphoma, run by Rennes University Hospital at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2019.