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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Primary central nervous system lymphoma (PCNSL)

Cooperative Study Group

Study Group Freiburg

Scientific focus

Established in 1998, the German Cooperative Primary Central Nervous System Lymphoma (PCNSL) Study Group has conducted various clinical trials covering important questions in PCNSL treatment; be it in newly diagnosed, relapsed disease as well as elderly PCNSL patients. In each of these indications, the group has demonstrated a continuous track record - from early pilot studies investigating several immuno-chemotherapy protocols, which were subsequently improved and validated in large international multicenter studies and published in high-impact journals.

The German Cooperative PCNSL Study Group, located in Freiburg and Stuttgart, is currently conducting the  world’s largest randomized phase III MATRix/IELSG43 trial (330 patients from 35 centers) and has completed recruitment targets and challenges in consolidating high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) with conventionally dosed chemotherapy. A subsequent randomized phase III trial has already been designed with recruitment beginning early 2021. Another investigator-initiated pilot trial explored an elderly adapted approach with HCT-ASCT after short induction. The subsequent phase II MARTA trial has recently completed recruitment. The concept development phase of a subsequent randomized phase III trial is currently funded by the German Ministry of Research and Education. In addition to the described chemoimmunotherapy approaches, the group is currently running a bicentric phase IB trial investigating a chemotherapy-free regimen with venetoclax and obinutuzumab in relapsed and refractory PCNSL.

All PCNSL trials are accompanied by translational research programs (PI: Dr. F. Scherer). The major goal of these scientific projects is to establish molecular biomarkers that predict clinical outcomes and help understand the underlying biology of treatment response and treatment failure in PCNSL patients.

Trials- recruiting

VENOBI CNS- Chemotherapy free treatment with venetoclax and obinutuzumab for relapsed / refractory primary CNS lymphoma patients (VENOBI-CNS study) - A phase IB study to assess the pharmacokinetics in the cerebrospinal fluid-


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VENOBI-CNS Synopsis

Contact:

Trials in follow up

MATRix/IELSG43- High dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma - randomized phase III trial

Recruitment was finished August 2019


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MATRix / IELSG43 Synopsis

Contact:

  • Coordinating Principal Investigator: Prof. Dr. med. Gerald Illerhaus
  • Medical Trial Coordinator: Dr. med. Elisabeth Schorb (Freiburg)
  • Project management: Elvira Burger (ZKS, Freiburg)

MARTA - Age-adjusted high-dose chemotherapy and autologous stem cell transplant in elderly and fit primary CNS lymphoma patients

Recruitment was finished September 2020


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MARTA Synopsis

Contact:

  • Coordinating Principal Investigator: Dr. med. Elisabeth Schorb (Freiburg)
  • Deputy Principal Investigator: Prof. Dr. med. Gerald Illerhaus (Stuttgart)
  • Project management: Elvira Burger (ZKS, Freiburg)

Planned Trials

OptiMATe - Optimising MATRix: De-escalated induction treatment in newly diagnosed primary CNS lymphoma- a randomized phase III trial.

Start of recruitment: approximately Q2/2021


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OptiMATe Synopsis

Contact:

  • Coordinating Principal Investigator: Prof. Dr. med. Gerald Illerhaus (Stuttgart)
  • Deputy Principal Investigator: Dr. med. Elisabeth Schorb (Freiburg)
  • Project management: Elvira Burger (ZKS, Freiburg)
     

PRIMA-CNS - Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly CNS lymphoma patients - a randomized phase III trial

Start of recruitment: approximately Q3/2021


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PRIMA-CNS Synopsis

Contact:

  • Coordinating Principal Investigator: Dr. med. Elisabeth Schorb (Freiburg)
  • Deputy Principal Investigator: Prof. Dr. med. Gerald Illerhaus (Stuttgart)
  • Project management: Elvira Burger (ZKS, Freiburg)
     

FIORELLA - A randomized Phase II trial on comorbidity- and fitness-tailored treatment in elderly patients with newly diagnosed PCNSL (in cooperation with IELSG)

Start of recruitment: trial is already recruiting abroad, in Germany start of recruitment approximately Q2/2021


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FIORELLA Trial / IELSG45 Synopsis

Contact:

  • Coordinating Principal Investigator: Andrés J. Ferreri (Milano, Italy)
  • Study committee, Principal Investigator: Prof. Dr. med. Gerald Illerhaus (Stuttgart)
  • Project management: Elvira Burger (ZKS, Freiburg)
Principal Investigator

PD Dr. med. Elisabeth Schorb

Phone: +49 761 270 35360
Fax: +49 761 270 73570

E-Mail: elisabeth.schorb@uniklinik-freiburg.de

Prof. Dr. Jürgen Finke

E-Mail: juergen.finke@uniklinik-freiburg.de

Dr. med. Lisa Isbell
Clinician Scientist

Phone: +49 761 270 34020
E-Mail: lisa.isbell@uniklinik-freiburg.de

Heidi Fricker
Monitoring

Phone: +49 761 270 77390
Fax: +49 761 270 73570
E-Mail: heidi.fricker@uniklinik-freiburg.de

Natalie Malenica
Study Nurse

Phone: +49 761 270 72140
Fax: +49 761 270 73570
E-Mail: natalie.malenica@uniklinik-freiburg.de

Annika Vreden
Med. Doktorandin

E-Mail: annika.vreden@uniklinik-freiburg.de

Principal Investigator

Prof. Dr. Gerald Illerhaus

Phone: +49 711 278-30401
Fax: +49 711 278-30409
E-Mail: g.illerhaus@klinikum-stuttgart.de

Dr. med. Julia Wendler
Clinician Scientist

E-Mail:  j.wendler@klinikum-stuttgart.de

Dr. med. Stefan Trefz 
Clinician Scientist

E-Mail:  s.trefz@klinikum-stuttgart.de

Simone Neumaier
Clinician Scientist

E-Mail: s.neumaier@klinikum-stuttgart.de

Dr. Elke Valk
Project Coordinator

Phone: +49 711 278-30414
Telefax: +49 711 278-35649
E-Mail: e.valk@klinikum-stuttgart.de

Cora Steinheber
Study Nurse and Monitoring

Phone: +49 711 278-54720
Fax: +49 711 278-35649
E-Mail: c.steinheber@klinikum-stuttgart.de

Present and previous funding:

  • Bundesministerium für Bildung und Forschung (BMBF)
  • Else Kröner-Fresenius-Stiftung (EKFS)
  • Medizinische Fakultät – Albert-Ludwigs-Universität Freiburg

Internal collaborations:

  • Dr. Florian Scherer, Klinik für Innere Medizin I (coordination translational research program)
  • Zentrum für Klinische Studien (ZKS) Freiburg
  • Prof. Dr. Joachim Weis, CCCF, Selbsthilfeforschung
  • Dr. Christiane Schmucker, Institut für Evidenz in der Medizin (für Cochrane Deutschland Stiftung)

 

External collaborations:

  • Participating trial centers in Germany (n ~ 40)
  • International Extranodal Lymphom Study Group (IELSG) with all international trial sites
  • Dr. Kate Cwynarski (London, UK)
  • Dr. Andres Ferreri (Milano, Italy)
  • Dr. Christopher Fox (Nottingham, UK)
  • Prof. Dr. Matthias Backenstraß, Institut für Klinische Psychologie, Klinikum Stuttgart
  • Dr. Alexander Friedl, Geriatrisches Zentrum Stuttgart
  • Dr. Elina Henkes, Abteilung für Neuroradiologie, Klinikum Stuttgart
  • Prof. Dr. Martina Deckert, Institut für Neuropathologie, Universitätsklinikum Köln
  • Prof. Dr. Falko Fend, Institut für Pathologie, Universitätsklinikum Tübingen

Original research

*equal contribution

  1. High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study.
    Schorb E, Kasenda B, Ihorst G, Scherer F, Wendler J, Isbell L, Fricker H, Finke J, Illerhaus G
    Blood Advances 2020
     
  2. Ibrutinib in patients with relapsed/refractory central nervous system lymphoma: A retrospective single-centre analysis.
    Lauer EM, Waterhouse M, Braig M, Mutter J, Bleul S, Duque-Afonso J, Duyster J, Marks R, Reinacher PC, Prinz M, Illerhaus G, Finke J, Schorb E, Scherer F.
    Br J Haematol. 2020
     
  3. Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice.
    Schorb E, Fox CP, Kasenda B, Linton K, Martinez-Calle N, Calimeri T, Ninkovic S, Eyre TA, Cummin T, Smith J, Yallop D, De Marco B, Krampera M, Trefz S, Orsucci L, Fabbri A, Illerhaus G, Cwynarski K, Ferreri AJM
    Br J Haematol. 2020
     
  4. Age-adjusted high-dose chemotherapy and autologous stem cell transplant in elderly and fit primary CNS lymphoma patients
    Schorb E, Finke J, Ihorst G, Kasenda B, Fricker H, Illerhaus G
    BMC Cancer. 2019
     
  5. Rituximab in primary central nervous system lymphoma - A systematic review and meta-analysis.
    Schmitt AM, Herbrand AK, Fox CP, Bakunina K, Bromberg JEC, Cwynarski K, Doorduijn JK, Ferreri AJM, Illerhaus G, Issa S, Schorb E, Zucca E, Hemkens LG, Schandelmaier S, Kasenda B.
    Hematol Oncol. 2019
     
  6. The MRZ reaction and a quantitative intrathecal IgG synthesis may be helpful to differentiate between primary central nervous system lymphoma and multiple sclerosis.
    Hottenrott T*, Schorb E*, Fritsch K, Dersch R, Berger B, Huzly D, Rauer S, Tebartz van Elst L, Endres D, Stich O.
    J Neurol. 2018
     
  7. Hyper N-glycosylated SAMD14 and neurabin-I as driver CNS autoantigens of PCNSL.
    Thurner L, Preuss KD, Bewarder M, Kemele M, Fadle N, Regitz E, Altmeyer S, Schormann C, Poeschel V, Ziepert M, Walter S, Roth P, Weller M, Szczepanowski M, Klapper W, Monoranu C, Rosenwald A, Möller P, Hartmann S, Hansmann ML, Mackensen A, Schäfer H, Schorb E, Illerhaus G, Buslei R, Bohle RM, Stilgenbauer S, Kim YJ, Pfreundschuh M.
    Blood. 2018
     
  8. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial.
    Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosée P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sønderskov Gørløv J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG).
    Lancet Haematol. 2017
     
  9. High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study.
    Schorb E, Fox CP, Fritsch K, Isbell L, Neubauer A, Tzalavras A, Witherall R, Choquet S, Kuittinen O, De-Silva D, Cwynarski K, Houillier C, Hoang-Xuan K, Touitou V, Cassoux N, Marolleau JP, Tamburini J, Houot R, Delwail V, Illerhaus G, Soussain C, Kasenda B.
    Bone Marrow Transplant. 2017
     
  10. High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group.
    Kasenda B, Ihorst G, Schroers R, Korfel A, Schmidt-Wolf I, Egerer G, von Baumgarten L, Röth A, Bloehdorn J, Möhle R, Binder M, Keller U, Lamprecht M, Pfreundschuh M, Valk E, Fricker H, Schorb E, Fritsch K, Finke J, Illerhaus G.
    Leukemia. 2017
     
  11. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).
    Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, Löw S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Heß G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Röth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G.
    Leukemia. 2017
     
  12. High-dose chemotherapy and autologous stem cell transplant compared with conventional chemotherapy for consolidation in newly diagnosed primary CNS lymphoma--a randomized phase III trial (MATRix).
    Schorb E, Finke J, Ferreri AJ, Ihorst G, Mikesch K, Kasenda B, Fritsch K, Fricker H, Burger E, Grishina O, Valk E, Zucca E, Illerhaus G.
    BMC Cancer. 2016
     
  13. High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial.
    Illerhaus G, Kasenda B, Ihorst G, Egerer G, Lamprecht M, Keller U, Wolf HH, Hirt C, Stilgenbauer S, Binder M, Hau P, Edinger M, Frickhofen N, Bentz M, Möhle R, Röth A, Pfreundschuh M, von Baumgarten L, Deckert M, Hader C, Fricker H, Valk E, Schorb E, Fritsch K, Finke J.
    Lancet Haematol. 2016
     
  14. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.
    Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG).
    Lancet Haematol. 2016
     
  15. Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation.
    Schorb E, Kasenda B, Atta J, Kaun S, Morgner A, Hess G, Elter T, von Bubnoff N, Dreyling M, Ringhoffer M, Krause SW, Derigs G, Klimm B, Niemann D, Fritsch K, Finke J, Illerhaus G.
    Haematologica. 2013
     
  16. Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma.
    Doolittle ND, Korfel A, Lubow MA, Schorb E, Schlegel U, Rogowski S, Fu R, Dósa E, Illerhaus G, Kraemer DF, Muldoon LL, Calabrese P, Hedrick N, Tyson RM, Jahnke K, Maron LM, Butler RW, Neuwelt EA.
    Neurology. 2013
     
  17. 18F-FDG PET is an independent outcome predictor in primary central nervous system lymphoma.
    Kasenda B, Haug V, Schorb E, Fritsch K, Finke J, Mix M, Hader C, Weber WA, Illerhaus G, Meyer PT.
    J Nucl Med. 2013
     
  18. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study.
    Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G.
    Ann Oncol. 2012
     
  19. The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients.
    Kasenda B, Rehberg M, Thürmann P, Franzem M, Veelken H, Fritsch K, Schorb E, Finke J, Lebiedz D, Illerhaus G.
    Ann Hematol. 2012
     

Case reports

Reviews

  1. Aktuelle Therapiestandards primärer ZNS Lymphome
    Schorb E, Illerhaus G, Finke J
    Dtsch Med Wochenschr 2019
  2. Novel agents for primary central nervous system lymphoma (PCNSL) - evidence and perspectives - Invited review.
    Illerhaus G, Schorb E, Kasenda B
    Blood. 2018

Books

  • Das Primäre ZNS-Lymphom
    Illerhaus G, Kasenda B, Schorb E
    UNI-MED Verlag AG; Auflage 1, 2019

  • Advanced Clinican Scientist Award, Medizinische Fakultät Freiburg
  • Clinical Research Training in Hematology Award, European Hematology Association (EHA)
  • International PCNSL Cooperative Group Travel Scholarship Award
PD Dr. Elisabeth Schorb
Dr. Elisabeth Schorb

Principal Investigator

E-Mail: elisabeth.schorb@uniklinik-freiburg.de

Phone: +49 761 270 35360 oder -34010

Universitätsklinikum Freiburg
Klinik für Innere Medizin I
Hugstetter Straße 55
D-79106 Freiburg

Elvira Burger
Elvira Burger

Project Management

Telefon: +49 761 270-73780
Telefax: +49 761 270-73770
E-Mailelvira.burger@uniklinik-freiburg.de

Universitätsklinikum Freiburg
Studienzentrum (ZKS)
Elsässer Straße 2
79106 Freiburg