Genomic and Proteomic Study of Richter Syndrome (CGPSR)

NCT ID: NCT03619512

Last Updated: 2023-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

170 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-06

Study Completion Date

2024-09-05

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Richter Syndrome

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Richter Syndrom at diagnosis

patients diagnosed with Richter Syndrom, for whom a suitable lymph node biopsy at diagnosis is available.

Whole exome sequencing.

Intervention Type GENETIC

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

RNA sequencing

Intervention Type GENETIC

Characterization of tumor transcriptomic profile.

Mass spectrometry

Intervention Type OTHER

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.

Whole exome sequencing.

Intervention Type GENETIC

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

RNA sequencing

Intervention Type GENETIC

Characterization of tumor transcriptomic profile.

Mass spectrometry

Intervention Type OTHER

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.

Whole exome sequencing.

Intervention Type GENETIC

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

RNA sequencing

Intervention Type GENETIC

Characterization of tumor transcriptomic profile.

Mass spectrometry

Intervention Type OTHER

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.

Whole exome sequencing.

Intervention Type GENETIC

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

RNA sequencing

Intervention Type GENETIC

Characterization of tumor transcriptomic profile.

Mass spectrometry

Intervention Type OTHER

Characterization of tumor proteomic profiles.

Interventions

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Whole exome sequencing.

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

Intervention Type GENETIC

RNA sequencing

Characterization of tumor transcriptomic profile.

Intervention Type GENETIC

Mass spectrometry

Characterization of tumor proteomic profiles.

Intervention Type OTHER

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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French Innovative Leukemia Organization (FILO)

UNKNOWN

Sponsor Role collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julien Broseus, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Central Hospital, Nancy, France

Pierre Feugier, MD, PhD

Role: STUDY_DIRECTOR

Central Hospital, Nancy, France

Locations

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CHRU de Nancy

Nancy, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Julien Broseus, MD, PhD

Role: CONTACT

+ 33 (0)3 83 15 49 14

Véronique Saunier

Role: CONTACT

+ 33 (0)3 83 15 54 58

Facility Contacts

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Véronique SAUNIER

Role: primary

+33 (0)3 83 15 54 58

References

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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.

Reference Type BACKGROUND
PMID: 21796624 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24265505 (View on PubMed)

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.

Reference Type RESULT
PMID: 18492108 (View on PubMed)

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.

Reference Type RESULT
PMID: 23841899 (View on PubMed)

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.

Reference Type RESULT
PMID: 21266718 (View on PubMed)

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.

Reference Type RESULT
PMID: 21417856 (View on PubMed)

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.

Reference Type RESULT
PMID: 22571487 (View on PubMed)

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.

Reference Type RESULT
PMID: 21670202 (View on PubMed)

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.

Reference Type RESULT
PMID: 24004666 (View on PubMed)

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.

Reference Type RESULT
PMID: 20014148 (View on PubMed)

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.

Reference Type RESULT
PMID: 24127483 (View on PubMed)

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.

Reference Type RESULT
PMID: 10676951 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34000073 (View on PubMed)

Other Identifiers

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PSS2017/CGPSR-BROSÉUS/VS

Identifier Type: OTHER

Identifier Source: secondary_id

2017-A01978-45

Identifier Type: -

Identifier Source: org_study_id

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