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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Rennes University Hospital
Sponsor:
Collaborators:
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
National Cancer Institute, France
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01287923
First received: January 31, 2011
Last updated: August 5, 2014
Last verified: August 2014
  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
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Identify a prognostic whole blood RNA signature related to aggressive DLBCL [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Proportion and phenotypic characteristics of circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Immune functions of these circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL [ Time Frame: 3 years ] [ Designated as safety issue: No ]

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.


Estimated Enrollment: 400
Study Start Date: February 2010
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287923

Contacts
Contact: Thierry Fest, MD 02.99.28.42.72 thierry.fest@chu-rennes.fr
Contact: Delphine Rossille, PhD 02.99.28.43.21 ext 89938 delphine.rossille@chu-rennes.fr

Locations
France
Amiens University Hospital Recruiting
Amiens, France, 80054
Contact: Ghandi Damaj, MD    03.22.45.59.15    damaj.ghandi@chu-amiens.fr   
Principal Investigator: Ghandi Damaj, MD         
Angers University Hospital Recruiting
Angers, France, MD
Contact: Charles Foussard, MD    02.41.35.45.24    chfoussard@chu-angers.fr   
Principal Investigator: Charles Foussard, MD         
Victor Dupouy Hospital Recruiting
Argenteuil, France, 95100
Contact: Ahmad Al Jijakli, MD    01.34.23.20.19    ahmad.aljijakli@ch-argenteuil.fr   
Principal Investigator: Ahmad Al Jijakli, MD         
Cesson-Sévigné Clinic Recruiting
Cesson-Sévigné, France, 35576
Contact: Benoît Bareau, MD       benoit.bareau@gmail.com   
Principal Investigator: Benoît Bareau, MD         
La Roche-sur-Yon Hospital Recruiting
La Roche-sur-Yon, France, 85025
Contact: Hervé Maisonneuve, MD    02.51.44.61.73    oncohemato@chd-vendee.fr   
Principal Investigator: Hervé Maisonneuve, MD         
Lille University Hospital Recruiting
Lille, France, 59037
Contact: Franck Morschhauser, MD       franck.morschhauser@chru-lille.fr   
Principal Investigator: Franck Morschhauser, MD         
Lorient Hospital Recruiting
Lorient, France, 56100
Contact: Philippe Moreau, MD    02.97.64.91.85    p.moreau@ch-bretagne-sud.fr   
Principal Investigator: Philippe Moreau, MD         
Nantes University Hospital (Hôtel-Dieu) Recruiting
Nantes, France, 44093
Contact: Steven Le Gouill, MD    02.40.08.32.63    steven.legouill@chu-nantes.fr   
Principal Investigator: Steven Le Gouill, MD         
Bordeaux University Hospital ( Haut-Lévêque Hospital) Recruiting
Pessac, France, 33604
Contact: Noël Milpied, MD    05.57.65.66.57    noel.milpied@chu-bordeaux.fr   
Contact: Kamal Bouabdallah, MD    05.57.65.66.57    krimo.boubdallah@chu-bordeaux.fr   
Principal Investigator: Noël Milpied, MD         
Sub-Investigator: Kamal Bouabdallah, MD         
Poitiers University Hospital Recruiting
Poitiers, France, MD
Contact: Vincent Delwail, MD    05.49.44.44.72    v.delwail@chu-poitiers.fr   
Principal Investigator: Vincent Delwail, MD         
Rennes University Hospital Recruiting
Rennes, France, 35000
Contact: Thierry Lamy, MD    02.99.28.42.91    thierry.lamy@chu-rennes.fr   
Contact: Xavier Cahu, MD    02.99.28.42.91    xavier.cahu@chu-rennes.fr   
Principal Investigator: Thierry Lamy, MD         
Sub-Investigator: Xavier Cahu, MD         
Principal Investigator: Yves le Tulzo, MD         
Rennes EFS Recruiting
Rennes, France, 35000
Contact: Gilbert Semana, MD    02.99.54.42.22    gilbert.semana@univ-rennes1.fr   
Principal Investigator: Gilbert Semana, MD         
Saint-Brieuc Hospital Recruiting
Saint-Brieuc, France, 22000
Contact: Olivier Allangba, MD    02.96.01.70.84    olivier.allangba@ch-stbrieuc.fr   
Principal Investigator: Olivier Allangba, MD         
Saint-Malo Hospital Recruiting
Saint-Malo, France, 35400
Contact: Isabelle Grulois, MD    02.99.21.29.23    i.grulois@ch-stmalo.fr   
Principal Investigator: Isabelle Grulois, MD         
Loire Cancer Institute Recruiting
Saint-Priez-en-Jarez, France, 42271
Contact: Jérôme Cornillon, MD    04.77.91.70.60    jerome.cornillon@icloire.fr   
Principal Investigator: Jérôme Cornillon, MD         
Toulouse University Hospital Recruiting
Toulouse, France, 35059
Contact: Loïc Ysebaert, md       ysebaert@chu-toulouse.fr   
Principal Investigator: Loïc Ysebaert, MD         
Vannes Hospital Recruiting
Vannes, France, 56000
Contact: Henry Jardel, MD    02.97.01.47.79    henry.jardel@ch-bretagne-atlantique.fr   
Principal Investigator: Henry Jardel, MD         
Sponsors and Collaborators
Rennes University Hospital
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
National Cancer Institute, France
Investigators
Principal Investigator: Thierry Fest, MD Rennes University Hospital
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01287923     History of Changes
Other Study ID Numbers: 2010-A00812-37, TRANS/10-01, B101038-10
Study First Received: January 31, 2011
Last Updated: August 5, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
Hematology
Secondary lymphoid organs

ClinicalTrials.gov processed this record on October 22, 2014