Assessment of Blood Biomarkers by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans

DLBCL Clinical Trial

— BMS-LyTrans  

Official title:

Assessment of Biomarkers Initially Identified in Whole Blood by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01287923
• Other study ID #: 2010-A00812-37
• Secondary ID: TRANS/10-01B1010
• Status: Completed
• First received: January 31, 2011
• Last updated: April 6, 2018
• Start date: February 21, 2011
• Est. completion date: September 1, 2017

Study information

• Verified date: April 2018
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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. Coordinating nvestigator hypothesized that blood may be a deep source of native and secreted analytes and therefore carries transcriptomic signatures related to DLBCL and its prognosis. This project is organized in the extension of the GOELAMS-075 clinical trial which concerns aggressive DLBCL.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 326
• Est. completion date: September 1, 2017
• Est. primary completion date: June 8, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• DLBCL

Locations

Country	Name	City	State
France	Amiens University Hospital	Amiens
France	Angers University Hospital	Angers
France	Victor Dupouy Hospital	Argenteuil
France	Cesson-Sévigné Clinic	Cesson-Sévigné
France	La Roche-sur-Yon Hospital	La Roche-sur-Yon
France	Lille University Hospital	Lille
France	Lorient Hospital	Lorient
France	Nantes University Hospital (Hôtel-Dieu)	Nantes
France	Bordeaux University Hospital ( Haut-Lévêque Hospital)	Pessac
France	Poitiers University Hospital	Poitiers
France	Rennes EFS	Rennes
France	Rennes University Hospital	Rennes
France	Saint-Brieuc Hospital	Saint-Brieuc
France	Saint-Malo Hospital	Saint-Malo
France	Loire Cancer Institute	Saint-Priest-en-Jarez
France	Toulouse University Hospital	Toulouse
France	Vannes Hospital	Vannes

Sponsors (3)

Lead Sponsor	Collaborator
Rennes University Hospital	French Innovative Leukemia Organisation, National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Research for cancer-related biomarkers	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.	3 years
Secondary	Sensitivity & specificity of the identified molecular signature in the DLBCL diagnosis context	Sensitivity & specificity of the identified molecular signature in the DLBCL	3 years
Secondary	Identify a prognostic whole blood RNA signature related to aggressive DLBCL	Identify a prognostic whole blood RNA signature related to aggressive DLBCL	3 years
Secondary	Proportion and phenotypic characteristics of circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL	Proportion and phenotypic characteristics of circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL	3 years
Secondary	Immune functions of these 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	3 years