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Assessment of Biomarkers Initially Identified in Whole Blood by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans (BMS-LyTrans)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01287923
First Posted: February 2, 2011
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
French Innovative Leukemia Organisation
National Cancer Institute, France
Information provided by (Responsible Party):
Rennes University Hospital
  Purpose

Diffuse Large B-cell Lymphoma (DLBCL) is the most frequent high grade lymphoma in adults. Although immunotherapy has improved its prognosis, DLBCL is a heterogeneous disease with patients exhibiting a wide range of outcomes with a 5-year overall survival ranging between 55 to 94% depending of the International Prognostic Index factor. Diagnostic and prognostic biomarkers are mandatory to optimize treatment. Transcriptomics has been used to detect such new biomarkers using microarrays analyses applied to RNA collected from total tumor tissues or cell extracts. Molecular prognostic factors have been thoroughly studied in DLBCL tumor tissues. However, it is a big challenge to obtain transcriptomic-qualified tumor samples in a multicentric and prospective clinical trial. We hypothesized that blood may be a deep source of native and secreted analytes and therefore carries transcriptomic signatures related to DLBCL and its prognosis. Our project is organized in the extension of the GOELAMS-075 clinical trial which concerns aggressive DLBCL.

Two complementary approaches will be followed, one at the transcriptomic level for confirmation of diagnostic biomarkers and to assess for predictive biomarkers. The other one concern biologic studies to validate our biomarkers at the tissue level. Our project will be organized around 4 workpackages (WP), each of them includes tasks with a specific schedule & predefined deliverables. The first one concerns the general management, data warehouse, collections and different administrative and preanalytic issues. The 3 other WPs are scientific. We are first going to validate a 30-gene list, candidate diagnostic biomarkers, by qRT-PCR on: *) an independent set of DLBCLs compared to matched healthy blood donors (sensitivity assessment) and, **) on a series of low tumor burden DLBCLs, mantle cell lymphomas and non-malignant inflammatory disease constituted by patients with a septic shock (specificity assessment). All this latter collections are already available and ready to use. Secondly, we will complete our series of 89 hybridized patients on AFFY WholeExon microarrays by 60 supplementary and available samples in order to assess for molecular predictor of patient outcome. This question will be address based on the 3-year and 5-year as well, EFS (Event Free Survivor). All the clinical data are available through the GOELAMS eCRF. Since we dispose of a 31 probesets, 30 single genes, signature for the DLBCL diagnosis that involves 9 genes related to the myeloid compartment including 6 genes involved directly or not to the Myeloid-Derived Cell Suppression (MDSC) process, 20 genes described in the context of the cancer and, 11 genes connected to endothelial cells, we decided to explore by flow cytometry blood circulating cells. We will look for myeloid populations & subpopulations, endothelial cells and microparticles. The goal is the identification of specific MDSC perturbations, angiogenic abnormalities and functional impacts on the immune response in the context of the cancer.

We expect by our work to drive both basic science and clinical implications. On the scientific level, blood carries molecular and cellular components involved in tumor-host interactions. Our project should bring a deeper understanding in the immunological response that takes place in the blood compartment. This immunological response will be characterized on a molecular, cellular and functional level. On a clinical point of view, it may bring a new prognostic model in DLBCL. As blood is easily accessible, we expect it to be easily implemented in clinical practice and to allow the design of new clinical trials stratified on tumor biology features. It may also become a new way to monitor DLBCL's response to treatment. Furthermore, this project will provide a large amount of molecular data that can be easily connected with other ongoing GOELAMS studies. Valorisation of our findings will also be serious issue since our project is highly original and valuable.


Condition
DLBCL

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Other
Official Title: Assessment of Biomarkers Initially Identified in Whole Blood by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Research for cancer-related biomarkers [ Time Frame: 3 years ]
    In this project we propose two complementary approaches with a first one orientated to the continuum of our current findings based on genes differentially expressed in blood between DLBCL patients and healthy people and a second one which takes in account the power and originality of our 075 GOELAMS cohort and will be focused on the research of predictive signatures of the DLBCL. We will go beyond the sole transcriptomic approach and also look for relevant cell biology clues.


Secondary Outcome Measures:
  • Sensitivity & specificity of the identified molecular signature in the DLBCL diagnosis context [ Time Frame: 3 years ]
    Sensitivity & specificity of the identified molecular signature in the DLBCL

  • Identify a prognostic whole blood RNA signature related to aggressive DLBCL [ Time Frame: 3 years ]
    Identify a prognostic whole blood RNA signature related to aggressive DLBCL

  • Proportion and phenotypic characteristics of circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL [ Time Frame: 3 years ]
    Proportion and phenotypic characteristics of circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL

  • Immune functions of these circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL [ Time Frame: 3 years ]
    Immune functions of these circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL


Biospecimen Retention:   Samples With DNA

For this study, 4 newly included cohorts are necesseray :

  • 100 new DLBCL patients are necessary. The blood will be taken at the diagnosis for DLBCL patients included 075-GOELAMS trial or 075-like patient.
  • 100 healthy blood donors. This cohort of matched for sex & gender will be constituted at the EFS (French Blood Bank) of Rennes.
  • 100 septic patients included at the Rennes University Hospital.
  • 100 075-like DLBCL patients in completed remission.

This project will also used already available blood collections: 2) Mantle cell lymphoma, 3) localized DLBCL and septic shock. Paraffin blocks of patient 075-trial DLBCLs are in the GOELAMSthèque bank localized in the Pathology Department Hôtel Dieu, Paris supervised by Pr Diane Damotte. Tissue Microarrays and complete paraffin blocks as well as some -80° tumors are already available.


Enrollment: 326
Actual Study Start Date: February 21, 2011
Study Completion Date: September 1, 2017
Primary Completion Date: June 8, 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
DLBCL
DLBCL patients included 075-GOELAMS trial or 075-like patient.
Healthy controls
Blood donors from the EFS (French Blood Bank) of Rennes.
Septic patients
septic patients included at the Rennes University Hospital.
DLBCL in completed remission
DLBCL patients from the 075 GOELAMS study in completed remission.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
DLBCL or Healthy blood donors or septic patient or GOELAMS 075 patients in completed remission
Criteria

Inclusion Criteria:

  • DLBCL or Healthy blood donors or septic patient or GOELAMS 075 patients in completed remission
  • Written informed consent

Exclusion Criteria:

  • Age < 18 or > 70
  • Not written informed consent
  • Not affiliated with social security
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01287923


Locations
France
Amiens University Hospital
Amiens, France, 80054
Angers University Hospital
Angers, France, MD
Victor Dupouy Hospital
Argenteuil, France, 95100
Cesson-Sévigné Clinic
Cesson-Sévigné, France, 35576
La Roche-sur-Yon Hospital
La Roche-sur-Yon, France, 85025
Lille University Hospital
Lille, France, 59037
Lorient Hospital
Lorient, France, 56100
Nantes University Hospital (Hôtel-Dieu)
Nantes, France, 44093
Bordeaux University Hospital ( Haut-Lévêque Hospital)
Pessac, France, 33604
Poitiers University Hospital
Poitiers, France, MD
Rennes EFS
Rennes, France, 35000
Rennes University Hospital
Rennes, France, 35000
Saint-Brieuc Hospital
Saint-Brieuc, France, 22000
Saint-Malo Hospital
Saint-Malo, France, 35400
Loire Cancer Institute
Saint-Priest-en-Jarez, France, 42271
Toulouse University Hospital
Toulouse, France, 35059
Vannes Hospital
Vannes, France, 56000
Sponsors and Collaborators
Rennes University Hospital
French Innovative Leukemia Organisation
National Cancer Institute, France
Investigators
Principal Investigator: Thierry Fest, MD Rennes University Hospital
  More Information

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01287923     History of Changes
Other Study ID Numbers: 2010-A00812-37
TRANS/10-01 ( Other Identifier: Sponsor : Rennes University Hospital )
B101038-10 ( Other Identifier: AFSSAPS References )
First Submitted: January 31, 2011
First Posted: February 2, 2011
Last Update Posted: October 17, 2017
Last Verified: October 2017

Keywords provided by Rennes University Hospital:
Hematology
Secondary lymphoid organs