Clinical trial NCT01287923: Assessment of Blood Biomarkers by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans
Official title: Assessment of Biomarkers Initially Identified in Whole Blood by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: DLBCL
Keywords: Hematology
Secondary lymphoid organs
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: French Innovative Leukemia Organisation
name: National Cancer Institute, France
First posted: 2011-02-02
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: DLBCL or Healthy blood donors or septic patient or GOELAMS 075 patients in completed remission

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Research for cancer-related biomarkers
timeFrame: 3 years
Secondary outcomes:
measure: Sensitivity & specificity of the identified molecular signature in the DLBCL diagnosis context
timeFrame: 3 years
measure: Identify a prognostic whole blood RNA signature related to aggressive DLBCL
timeFrame: 3 years
measure: Proportion and phenotypic characteristics of circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL
timeFrame: 3 years
measure: Immune functions of these circulating cells expressing the previously identified biomarkers at the time of diagnosis of DLBCL
timeFrame: 3 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Amiens University Hospital
city: Angers
country: France
facility: Angers University Hospital
city: Argenteuil
country: France
facility: Victor Dupouy Hospital
city: Cesson-Sévigné
country: France
facility: Cesson-Sévigné Clinic
city: La Roche-sur-Yon
country: France
facility: La Roche-sur-Yon Hospital
city: Lille
country: France
facility: Lille University Hospital
city: Lorient
country: France
facility: Lorient Hospital
city: Nantes
country: France
facility: Nantes University Hospital (Hôtel-Dieu)
city: Pessac
country: France
facility: Bordeaux University Hospital ( Haut-Lévêque Hospital)
city: Poitiers
country: France
facility: Poitiers University Hospital
city: Rennes
country: France
facility: Rennes EFS
city: Rennes
country: France
facility: Rennes University Hospital
city: Saint-Brieuc
country: France
facility: Saint-Brieuc Hospital
city: Saint-Malo
country: France
facility: Saint-Malo Hospital
city: Saint-Priest-en-Jarez
country: France
facility: Loire Cancer Institute
city: Toulouse
country: France
facility: Toulouse University Hospital
city: Vannes
country: France
facility: Vannes Hospital
Study officials:
affiliation: Rennes University Hospital
name: Thierry Fest, MD
role: PRINCIPAL_INVESTIGATOR
References: