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Richter SyndromeCGPSRNCT03619512

Genomic and Proteomic Study of Richter Syndrome (CGPSR)

An observational study of Richter Syndrome, run by Central Hospital, Nancy, France at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Any ageHealthy volunteers can take part
Conditions the study is for
Richter Syndrome
What is being tested?
Whole exome sequencing., RNA sequencing and Mass spectrometry
How many people
170 participants
Where
1 siteFrance
Study dates
6 Sep 2017to 5 Sep 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

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).

Who may be able to join

  • 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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Julien Broseus, MD, PhD contact

+ 33 (0)3 83 15 49 14

j.broseus@chru-nancy.fr

Véronique Saunier contact

+ 33 (0)3 83 15 54 58

v.saunier@chru-nancy.fr

France1 site, 1 recruiting

  • CHRU de Nancy

    Nancy, 54035

    Véronique SAUNIER, +33 (0)3 83 15 54 58, v.saunier@chru-nancy.fr

    Julien Broséus, MD, PhD

    Recruiting

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
Whole exome sequencing., RNA sequencing, Mass spectrometry
Keywords
Richter Syndrome, Genomics, Proteomics, Chemotherapy resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Whole exome sequencing.Genetic

    Retrospective biological exploration of the samples, including tumoral DNA exploration.

  • RNA sequencingGenetic

    Characterization of tumor transcriptomic profile.

  • Mass spectrometryOther

    Characterization of tumor proteomic profiles.

Study groups in NCT03619512
Study groupRoleWhat they receive
Richter Syndrom at diagnosispatients diagnosed with Richter Syndrom, for whom a suitable lymph node biopsy at diagnosis is available.
Receives: Genetic: Whole exome sequencing.; Genetic: RNA sequencing; Other: Mass spectrometry
Primitive Diffuse Large B-Cell Lymphomapatients diagnosed with a primitive Large B-Cell Lymphoma, for whom a suitable lymph node biopsy at diagnosis is available.
Receives: Genetic: Whole exome sequencing.; Genetic: RNA sequencing; Other: Mass spectrometry
Other secundary Diffuse Large B-Cell Lymphomapatients diagnosed with a secundary Large B-Cell Lymphoma (different from Richter Syndrom), for whom a suitable lymph node biopsy at diagnosis is available.
Receives: Genetic: Whole exome sequencing.; Genetic: RNA sequencing; Other: Mass spectrometry
Control group with no tumor involvment of lymph nodespatients for whom a diagnostic lymph node biopsy has been performed, which did not conclude to any tumoral lymph node involvment.
Receives: Genetic: Whole exome sequencing.; Genetic: RNA sequencing; Other: Mass spectrometry

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Whole exome sequencing data using next generation sequencing method

    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".

    Measured: 3 years

  2. RNA sequencing data using next generation sequencing method

    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.

    Measured: 3 years

  3. Proteomic analysis using mass spectrometry

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2018
  2. Study start6 Sep 2017
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion5 Sep 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03619512
Sponsor's protocol ID
2017-A01978-45
Other IDs
PSS2017/CGPSR-BROSÉUS/VS
Acronym
CGPSR
Status last verified
Mar 2023
First submitted
19 Jul 2018
Last updated
24 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rossi D, Spina V, Forconi F, Capello D, Fangazio M, Rasi S, Martini M, Gattei V, Ramponi A, Larocca LM, Bertoni F, Gaidano G. Molecular history of Richter syndrome: origin from a cell already present at the time of chronic lymphocytic leukemia diagnosis. Int J Cancer. 2012 Jun 15;130(12):3006-10. doi: 10.1002/ijc.26322. Epub 2011 Aug 25.

    PubMed 21796624

  • Ferreira PG, Jares P, Rico D, Gomez-Lopez G, Martinez-Trillos A, Villamor N, Ecker S, Gonzalez-Perez A, Knowles DG, Monlong J, Johnson R, Quesada V, Djebali S, Papasaikas P, Lopez-Guerra M, Colomer D, Royo C, Cazorla M, Pinyol M, Clot G, Aymerich M, Rozman M, Kulis M, Tamborero D, Gouin A, Blanc J, Gut M, Gut I, Puente XS, Pisano DG, Martin-Subero JI, Lopez-Bigas N, Lopez-Guillermo A, Valencia A, Lopez-Otin C, Campo E, Guigo R. Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia. Genome Res. 2014 Feb;24(2):212-26. doi: 10.1101/gr.152132.112. Epub 2013 Nov 21.

    PubMed 24265505

  • Rossi D, Cerri M, Capello D, Deambrogi C, Rossi FM, Zucchetto A, De Paoli L, Cresta S, Rasi S, Spina V, Franceschetti S, Lunghi M, Vendramin C, Bomben R, Ramponi A, Monga G, Conconi A, Magnani C, Gattei V, Gaidano G. Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. Br J Haematol. 2008 Jun;142(2):202-15. doi: 10.1111/j.1365-2141.2008.07166.x. Epub 2008 May 19.

    PubMed 18492108

  • Parikh SA, Rabe KG, Call TG, Zent CS, Habermann TM, Ding W, Leis JF, Schwager SM, Hanson CA, Macon WR, Kay NE, Slager SL, Shanafelt TD. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients. Br J Haematol. 2013 Sep;162(6):774-82. doi: 10.1111/bjh.12458. Epub 2013 Jul 11.

    PubMed 23841899

  • Rossi D, Spina V, Deambrogi C, Rasi S, Laurenti L, Stamatopoulos K, Arcaini L, Lucioni M, Rocque GB, Xu-Monette ZY, Visco C, Chang J, Chigrinova E, Forconi F, Marasca R, Besson C, Papadaki T, Paulli M, Larocca LM, Pileri SA, Gattei V, Bertoni F, Foa R, Young KH, Gaidano G. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood. 2011 Mar 24;117(12):3391-401. doi: 10.1182/blood-2010-09-302174. Epub 2011 Jan 25.

    PubMed 21266718

  • Fangazio M, De Paoli L, Rossi D, Gaidano G. Predictive markers and driving factors behind Richter syndrome development. Expert Rev Anticancer Ther. 2011 Mar;11(3):433-42. doi: 10.1586/era.10.237.

    PubMed 21417856

  • Rossi D, Rasi S, Spina V, Fangazio M, Monti S, Greco M, Ciardullo C, Fama R, Cresta S, Bruscaggin A, Laurenti L, Martini M, Musto P, Forconi F, Marasca R, Larocca LM, Foa R, Gaidano G. Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. Br J Haematol. 2012 Aug;158(3):426-9. doi: 10.1111/j.1365-2141.2012.09155.x. Epub 2012 May 10. No abstract available.

    PubMed 22571487

  • Fabbri G, Rasi S, Rossi D, Trifonov V, Khiabanian H, Ma J, Grunn A, Fangazio M, Capello D, Monti S, Cresta S, Gargiulo E, Forconi F, Guarini A, Arcaini L, Paulli M, Laurenti L, Larocca LM, Marasca R, Gattei V, Oscier D, Bertoni F, Mullighan CG, Foa R, Pasqualucci L, Rabadan R, Dalla-Favera R, Gaidano G. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med. 2011 Jul 4;208(7):1389-401. doi: 10.1084/jem.20110921. Epub 2011 Jun 13.

    PubMed 21670202

  • Chigrinova E, Rinaldi A, Kwee I, Rossi D, Rancoita PM, Strefford JC, Oscier D, Stamatopoulos K, Papadaki T, Berger F, Young KH, Murray F, Rosenquist R, Greiner TC, Chan WC, Orlandi EM, Lucioni M, Marasca R, Inghirami G, Ladetto M, Forconi F, Cogliatti S, Votavova H, Swerdlow SH, Stilgenbauer S, Piris MA, Matolcsy A, Spagnolo D, Nikitin E, Zamo A, Gattei V, Bhagat G, Ott G, Zucca E, Gaidano G, Bertoni F. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood. 2013 Oct 10;122(15):2673-82. doi: 10.1182/blood-2013-03-489518. Epub 2013 Sep 4.

    PubMed 24004666

  • Scandurra M, Rossi D, Deambrogi C, Rancoita PM, Chigrinova E, Mian M, Cerri M, Rasi S, Sozzi E, Forconi F, Ponzoni M, Moreno SM, Piris MA, Inghirami G, Zucca E, Gattei V, Rinaldi A, Kwee I, Gaidano G, Bertoni F. Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas. Hematol Oncol. 2010 Jun;28(2):62-7. doi: 10.1002/hon.932.

    PubMed 20014148

  • Fabbri G, Khiabanian H, Holmes AB, Wang J, Messina M, Mullighan CG, Pasqualucci L, Rabadan R, Dalla-Favera R. Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome. J Exp Med. 2013 Oct 21;210(11):2273-88. doi: 10.1084/jem.20131448. Epub 2013 Oct 14.

    PubMed 24127483

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 Feb 3;403(6769):503-11. doi: 10.1038/35000501.

    PubMed 10676951

  • Moulin C, Guillemin F, Remen T, Bouclet F, Hergalant S, Quinquenel A, Dartigeas C, Tausch E, Lazarian G, Blanchet O, Lomazzi S, Chapiro E, Schneider C, Nguyen-Khac F, Davi F, Hunault M, Tomowiak C, Roos-Weil D, Siebert R, Thieblemont C, Cymbalista F, Laribi K, Bene MC, Stilgenbauer S, Guieze R, Feugier P, Broseus J. Clinical, biological, and molecular genetic features of Richter syndrome and prognostic significance: A study of the French Innovative Leukemia Organization. Am J Hematol. 2021 Sep 1;96(9):E311-E314. doi: 10.1002/ajh.26239. Epub 2021 Jun 2. No abstract available.

    PubMed 34000073

Questions about this trial

What is this clinical trial studying?

An observational study of Richter Syndrome, run by Central Hospital, Nancy, France at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Julien Broseus, MD, PhD (+ 33 (0)3 83 15 49 14, j.broseus@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Whole exome sequencing data using next generation sequencing method (time frame: 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03619512, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.

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