Genomic and Proteomic Study of Richter Syndrome (CGPSR) (CGPSR)

March 23, 2023 updated by: Central Hospital, Nancy, France

Genomic and Proteomic Study of Richter Syndrome

Biological study on Richter Syndrome (RS), an agressive lymphoma that arises from Chronic Lymphocytice Leukemia (CLL). RS presents with the same histological aspect as primitive Diffuse Large B-Cell Lymphoma (DLBCL), but is associated with a poor prognosis, due to chemorefractoriness.

This study aims at understanding the biological determinants of chemotherapy resistance in Richter Syndrome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

With the help of the French National Research Group on CLL (FILO / French Innovative Leukemia Organization), the investigators are currently gathering fresh frozen cell pellets at CLL stage, and lymph node biopsies at Richter stage. The investigators also gathered lymph node biopsies from DLBCL, as a reference group.

The investigators will perform genomic and proteomic comparative studies between CLL and Richter, as well as between Richter and primitive DLBCL, to understand the biological determinants of clonal evolution and chemorefractoriness of Richter Syndrom.

Study Type

Observational

Enrollment (Anticipated)

170

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Nancy, France, 54035
        • Recruiting
        • CHRU de Nancy
        • Contact:
        • Principal Investigator:
          • Julien Broséus, MD, PhD
        • Sub-Investigator:
          • Pierre Feugier, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

  • Diagnosis of Diffuse Large B-Cell Lymphoma arising in the context of a Chronic Lymphocytic Leukemia (group 1).
  • Diagnosis of Diffuse Large B-Cell Lymphoma de novo (group 2).
  • Diagnosis of Diffuse Large B-Cell Lymphoma arising in a context of small cells lymphoma, excluding CLL (group 3).
  • Patients who benefited from a diagnostic lymph node biopsy that did not reveal any tumor involvment (primitive or metastatic) (group 4).

Description

Inclusion Criteria:

  • Diagnosis of a Diffuse Large B-Cell Lymphoma arising in the context of a Chronic Lymphocytic Leukemia (group 1) or diagnosis of a primitive Diffuse Large B-Cell Lymphoma (group 2), or diagnosis of a Diffuse Large B-Cell Lymphoma arising in a context of small cells lymphoma, excluding CLL (group 3), or benefit from a diagnostic lymph node biopsy that did not reveal any tumor involvment (primitive or metastatic) (group 4).
  • Patients must benefit from a lymph node biopsy at diagnosis.
  • Patients must be followed by a FILO (French Innovative Leukemia Organization) member
  • Histology of Diffuse Large B-Cell Lymphoma or Hodgkin histology.
  • Suitable clinical data available.
  • Samples must meet the following requirement :RIN (RNA Integrity Number) > 5 et DIN (DNA Integrity Number) > 6.5.

Exclusion Criteria:

• Samples that do not meet the inclusion criteria (insufficient clinical data, analysis impossible due to insufficient sample quality).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Richter Syndrom at diagnosis
patients diagnosed with Richter Syndrom, for whom a suitable lymph node biopsy at diagnosis is available.
Genetic: Whole exome sequencing.
Retrospective biological exploration of the samples, including tumoral DNA exploration.
Genetic: RNA sequencing
Characterization of tumor transcriptomic profile.
Other: Mass spectrometry
Characterization of tumor proteomic profiles.
Primitive Diffuse Large B-Cell Lymphoma
patients diagnosed with a primitive Large B-Cell Lymphoma, for whom a suitable lymph node biopsy at diagnosis is available.
Genetic: Whole exome sequencing.
Retrospective biological exploration of the samples, including tumoral DNA exploration.
Genetic: RNA sequencing
Characterization of tumor transcriptomic profile.
Other: Mass spectrometry
Characterization of tumor proteomic profiles.
Other secundary Diffuse Large B-Cell Lymphoma
patients diagnosed with a secundary Large B-Cell Lymphoma (different from Richter Syndrom), for whom a suitable lymph node biopsy at diagnosis is available.
Genetic: Whole exome sequencing.
Retrospective biological exploration of the samples, including tumoral DNA exploration.
Genetic: RNA sequencing
Characterization of tumor transcriptomic profile.
Other: Mass spectrometry
Characterization of tumor proteomic profiles.
Control group with no tumor involvment of lymph nodes
patients for whom a diagnostic lymph node biopsy has been performed, which did not conclude to any tumoral lymph node involvment.
Genetic: Whole exome sequencing.
Retrospective biological exploration of the samples, including tumoral DNA exploration.
Genetic: RNA sequencing
Characterization of tumor transcriptomic profile.
Other: Mass spectrometry
Characterization of tumor proteomic profiles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Whole exome sequencing data using next generation sequencing method
Time Frame: 3 years

Comparison between the DNA sequences from Richter syndrome samples and DNA sequences from primitive DLBCL samples to identify a set of mutations that are specific to Richter syndrome.

For each position, the result is "mutated" or "unmutated".
3 years
RNA sequencing data using next generation sequencing method
Time Frame: 3 years

Measurment of gene expression for all genes. Comparison of these expression levels between Richter samples, primitive DLBCL samples and normal lymph nodes to identifiy a set of genes which expression levels are different in Richter samples compared primitive DLBCL and normal lymph nodes.

Gene expression is a quatitative value. This set of genes forms a specific "transcriptomic signature" of Richter syndrome.
3 years
Proteomic analysis using mass spectrometry
Time Frame: 3 years

Mass spectrometry allows identification and measurment of the expression level of the 5,000 most expressed proteins in a sample. The investigators want to compare the protein expression levels between Richter samples, primitive DLBCL samples and normal lymph nodes to identifiy a set of proteins that are highly expressed in Richter samples (but not in primitive DLBCL or normal lymph nodes). This set of proteins forms a specific "proteomic signature" of Richter.

Protein expression is a quatitative value expressed as an absolute number of copies in a cell.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Central Hospital, Nancy, France

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
French Innovative Leukemia Organization (FILO)

Investigators

  • Principal Investigator: Julien Broseus, MD, PhD, Central Hospital, Nancy, France
  • Study Director: Pierre Feugier, MD, PhD, Central Hospital, Nancy, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 6, 2017

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

September 5, 2024

Study Registration Dates

First Submitted

July 19, 2018

First Submitted That Met QC Criteria

August 2, 2018

First Posted (Actual)

August 8, 2018

Study Record Updates

Last Update Posted (Actual)

March 24, 2023

Last Update Submitted That Met QC Criteria

March 23, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-A01978-45
  • PSS2017/CGPSR-BROSÉUS/VS (Other Identifier: CHRU Nancy)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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