ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma

December 17, 2017 updated by: Prof. Dr. M. Dreyling (co-chairman)

Autologous Transplantation After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma - a Randomized European Mcl Network Trial

The primary objective of the the trial is to establish one of three study arms, as future standard based on the comparison of the investigator-assessed failure-free survival.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Objectives and Endpoints

Primary Objective:

To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance experimental arm I) as future standard based on the comparison of the investigator-assessed failure-free survival (FFS).

Secondary Objectives:

  • To compare the efficacy of the three treatment arms in terms of secondary efficacy endpoints
  • To determine the safety and tolerability of ibrutinib during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints

Primary Endpoint:

FFS defined as time from start of treatment to stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause.

Secondary Efficacy Endpoints:

  • Overall survival (OS)
  • Progression-free survival (PFS) from randomization, from end of induction immuno-chemotherapy in patients with CR or PR at end of induction immuno-chemotherapy, and from the staging 6 weeks after end of induction assessment (at month 6)
  • Overall response and complete remission rates at midterm, at end of induction, 3 months after end of induction immunochemotherapy (at month 6)
  • PR to CR conversion rate during follow-up after end of induction immuno-chemotherapy

Secondary Toxicity Endpoints:

  • Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during induction immuno-chemotherapy and during periods of follow-up after response to immune-chemotherapy
  • Cumulative incidence rates of SPMs

Exploratory Objectives:

  • To compare feasibility of ASCT in arm A+I vs. arm A
  • To compare minimal residual disease status between the three treatment groups
  • To determine the impact of ibrutinib during induction immuno-chemotherapy and during maintenance therapy on the minimal residual disease status
  • To determine the prognostic value of minimal residual disease status
  • To determine the prognostic value of positron emission tomography with fluorine 18-fluorodeoxyglucose
  • To determine clinical and biological prognostic and predictive factors
  • To determine the role of total body irradiation (TBI) in ASCT conditioning

Exploratory Endpoints:

  • Rate of successful stem cell mobilisations (success: separation of at least 2x2x10(6) CD34-positive cells, including a back-up)
  • Rate of molecular remissions (MRD-negative patients) at midterm, at end of induction immuno-chemotherapy, and at staging time-points during follow-up in patients with remission after end of induction immuno-chemotherapy
  • Time to molecular remission from start of therapy
  • Time to molecular relapse for patients in clinical and molecular remission after end of induction immunochemotherapy
  • RD in FDG-PET negative or positive patients after induction and ASCT

Exploratory objectives may be evaluated only in a subset of patients according to local standards and resources.

Study Type

Interventional

Enrollment (Anticipated)

870

Phase

  • Phase 3

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

  • Denmark
      • Aalborg, Denmark, 9000
        • Not yet recruiting
        • Aalborg University Hospital, Dept of Hematology
        • Principal Investigator:
          • Herdis Larsen, Dr.
      • Aarhus C, Denmark, 8000
        • Not yet recruiting
        • Aarhus University Hospital, Dept of Hematology
        • Principal Investigator:
          • Hans Bentzen, Dr.
      • Copenhagen, Denmark, 2100
        • Not yet recruiting
        • Rigshospitalet, Clinic of Hematology
        • Principal Investigator:
          • Martin Hutchings, Dr.
      • Herlev, Denmark, 2730
        • Not yet recruiting
        • Herlev Hospital, Department of Hematology L121
        • Principal Investigator:
          • Pär Lars Josefsson
        • Sub-Investigator:
          • Danny Stoltenberg
      • Odense C, Denmark, 5000
        • Not yet recruiting
        • Odense University Hospital, Dept of Hematology X
        • Principal Investigator:
          • Jacob Haaber Christensen, Dr.
      • Roskilde, Denmark, 4000
        • Not yet recruiting
        • Sjaelland University Hospital, Dept of Hematology
        • Principal Investigator:
          • Christian Bjorn Poulsen, Dr.
  • Germany
      • Augsburg, Germany, 86156
        • Recruiting
        • Zentralklinik Augsburg, II. Med. Klinik, Hämatologie int. Onkologie
        • Principal Investigator:
          • Christian Schmid, PD Dr.
        • Sub-Investigator:
          • Andreas Rank, PD Dr.
      • Aurich, Germany, 26603
        • Recruiting
        • Onkologische Gemeinschaftspraxis Dr. Janssen/Dr. Reichert in der Ubbo-Emmius-Klinik
        • Principal Investigator:
          • Jan Janssen, Dr.
        • Sub-Investigator:
          • Dietmar Reichert, Dr.
      • Bayreuth, Germany, 95445
        • Recruiting
        • Klinikum Bayreuth, Klinik f. Onkologie und Hämatologie
        • Principal Investigator:
          • Alexander Kiani, Prof.
        • Sub-Investigator:
          • Armin Leitner, Dr.
      • Berlin, Germany, 10967
        • Recruiting
        • Vivantes Klinikum Am Urban, Klinik f. Innere Medizin, Hämatologie und Onkologie
        • Principal Investigator:
          • Christian Scholz, PD Dr.
        • Sub-Investigator:
          • Annette Dierig, Dr.
      • Berlin, Germany, 12200
        • Not yet recruiting
        • Charité Univ.-Medizin Berlin, Med. Klinik - Hämatologie, Onkologie und Tumorimmunologie
        • Principal Investigator:
          • Antonio Pezzutto, Prof.
        • Sub-Investigator:
          • Corinna Leng, Dr.
      • Berlin, Germany, 13125
        • Recruiting
        • Helios Klinikum Berlin-Buch, Hämatologie, Onkologie und Tumorimmunologie
        • Sub-Investigator:
          • Stephan Fuhrmann, Dr.
      • Bochum, Germany, 44892
        • Recruiting
        • Knappschaftskrankenhaus Bochum-Langendreer
        • Principal Investigator:
          • Wolff Schmiegel, Prof. Dr.
      • Bonn, Germany, 53127
        • Recruiting
        • Universitätsklinikum Bonn
        • Principal Investigator:
          • Matthias Zipfel, Dr.
        • Sub-Investigator:
          • Johannes Heiders, Dr.
        • Sub-Investigator:
          • Karin Mayer, Dr.
        • Sub-Investigator:
          • Roland Kronenberger, Dr.
      • Bremen, Germany, 28239
        • Recruiting
        • Diako ev. Diakonie-KH gGmbH, Med. Klinik II, Hämatologie und Onkologie
        • Principal Investigator:
          • Ralf U. Trappe, Prof.
        • Sub-Investigator:
          • Christoph Diekmann, Dr.
      • Chemnitz, Germany, 09113
        • Recruiting
        • Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin II
        • Principal Investigator:
          • Mathias Hänel, PD Dr.
        • Sub-Investigator:
          • Andreas Thiel
      • Deggendorf, Germany, 94469
        • Recruiting
        • DONAUISAR Klinikum Deggendorf, Innere Medizin II
        • Principal Investigator:
          • Nicolas Graf, PD Dr.
        • Sub-Investigator:
          • Regine Maier
      • Dortmund, Germany, 44137
        • Recruiting
        • St.-Johannes-Hospital
        • Principal Investigator:
          • Ralf G. Meyer, PD Dr.
        • Sub-Investigator:
          • Heidrun Hindahl, Dr.
        • Sub-Investigator:
          • Darina Kodzhabasheva, Dr.
        • Sub-Investigator:
          • Volker Hagen, Dr.
      • Dresden, Germany, 01307
        • Recruiting
        • Gemeinschaftspraxis Dr. Mohm und Prange-Krex - Fachärzte für Innere Medizin und Hämatologie und Onkologie
        • Principal Investigator:
          • Gabriele Prange-Krex, Dr.
        • Sub-Investigator:
          • Johannes Mohm, Dr.
      • Dresden, Germany, 01307
        • Recruiting
        • Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
        • Principal Investigator:
          • Frank Kroschinsky, Prof. Dr.
        • Sub-Investigator:
          • Rainer Ordemann, Prof. Dr.
        • Sub-Investigator:
          • Nael Alakel, Dr.
      • Düsseldorf, Germany, 40225
        • Recruiting
        • Universitätsklinikum Düsseldorf, Klinik f. Hämatologie, Onkologie und klinische Immunologie
        • Principal Investigator:
          • Guido Kobbe, Prof.
        • Sub-Investigator:
          • Mustafa Kondakci, Dr.
      • Düsseldorf, Germany, 40479
        • Recruiting
        • Marien Hospital Düsseldorf
        • Principal Investigator:
          • Aristoteles Giagounidis, Prof. Dr.
        • Sub-Investigator:
          • Maika Klaiber-Hakimi, Dr.
        • Sub-Investigator:
          • Stefanie Gröpper, Dr.
        • Sub-Investigator:
          • Daniela Fachin, Dr.
      • Erfurt, Germany, 99089
        • Recruiting
        • Helios Klinikum Erfurt GmbH, Zentrum f. Innere Medizin u. internistische Onkologie, Hämostaseologie
        • Principal Investigator:
          • Herbert G. Sayer, PD Dr.
        • Sub-Investigator:
          • Volker Schmidt, Dr.
        • Sub-Investigator:
          • Elke Richter, Dr.
      • Erlangen, Germany, 91054
        • Recruiting
        • Universitätsklinikum Erlangen, Med. Klinik 5, Hämatologie und internistische Onkologie
        • Principal Investigator:
          • Bernd Spriewald, Prof. Dr.
        • Sub-Investigator:
          • Stefan Krause, Prof. Dr.
        • Sub-Investigator:
          • Norbert Meidenbauer, Dr.
        • Sub-Investigator:
          • Katja San Nicoló, Dr.
      • Eschweiler, Germany, 52249
        • Recruiting
        • St.-Antonius-Hospital Eschweiler, Klinik für Hämatologie und Onkologie
        • Principal Investigator:
          • Peter Staib, PD Dr.
        • Sub-Investigator:
          • Frank Schlegel, Dr.
        • Sub-Investigator:
          • Susan Wehle-Ilka, Dr.
      • Essen, Germany, 45147
        • Recruiting
        • Universitätsklinikum Essen, Klinik f. Hämatologie
        • Principal Investigator:
          • Jan Dürig, Prof.
        • Sub-Investigator:
          • Alexander Carpinteiro, Dr.
        • Sub-Investigator:
          • Andreas Hüttmann, PD. Dr.
        • Sub-Investigator:
          • Alexander Röth, Dr.
        • Sub-Investigator:
          • Joachim R. Göthert, Dr.
        • Sub-Investigator:
          • Julia Baum, Dr.
      • Freiburg, Germany, 79106
        • Recruiting
        • Universitätsklinikum Freiburg, Klinik f. Innere Medizin, Hämatologie, Onkologie u. Stammzelltransplantation
        • Principal Investigator:
          • Reinhard Marks, PD Dr.
        • Sub-Investigator:
          • Anna-Lena Illert, Dr.
        • Sub-Investigator:
          • Cornelius Miething, Dr.
        • Sub-Investigator:
          • Stefanie Kreutmair, Dr.
        • Sub-Investigator:
          • Rainer Claus, PD Dr.
      • Greifswald, Germany, 17475
        • Recruiting
        • Universitätsmedizin Greifswald, Klinik u. Poliklinik f. Innere Medizin C, Hämatologie u. Onkologie-, Transplantationszentrum
        • Principal Investigator:
          • Christian Schmidt, Prof.
        • Sub-Investigator:
          • William Krüger, Prof.
        • Sub-Investigator:
          • Christian Späth, Dr.
        • Sub-Investigator:
          • Carsten Hirt, Dr.
      • Göttingen, Germany, 37075
        • Recruiting
        • Universitätsmedizin Göttingen, Zentrum f. Innere Medizin, Klinik f. Hämatologie und Medizinische Onkologie
        • Principal Investigator:
          • Wolfram Jung, Dr.
        • Sub-Investigator:
          • Justin Hasenkamp, Dr.
        • Sub-Investigator:
          • Gerald G. Wulf, Prof. Dr.
        • Sub-Investigator:
          • Friederike Braulke, Dr.
      • Hagen, Germany, 58095
        • Recruiting
        • Katholisches Krankenhaus Hagen gGmbH, St.-Marien-Hospital, Klinik f. Hämatologie und Onkologie
        • Principal Investigator:
          • Hans-Walter Lindemann, Dr.
        • Sub-Investigator:
          • Cordula Maciejewski
      • Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf (UKE), II. Med. Klinik u. Poliklinik, Onkologie, Hämatologie, KMT
        • Principal Investigator:
          • Judith Dierlamm, Prof.
        • Sub-Investigator:
          • Lars Arne Berger, Dr.
        • Sub-Investigator:
          • Carola Reimer, Dr.
        • Sub-Investigator:
          • Anja Coym, Dr.
      • Hamburg, Germany, 22763
        • Recruiting
        • Asklepios Klinik Altona, II. Med.Abt. f. Hämatologie und internistische Onkologie, Stammzelltransplantation
        • Principal Investigator:
          • Hans-Jürgen Salwender, Dr.
        • Sub-Investigator:
          • Murwan Ayoub, Dr.
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitätsklinikum Heidelberg, Med. Klinik - Innere Medizin V - Hämatologie, Onkologie und Rheumatologie
        • Principal Investigator:
          • Mathias Witzens-Harig, Prof.
        • Sub-Investigator:
          • Patrick Wuchter, Dr.
        • Sub-Investigator:
          • Iris Breitkreutz, Dr.
        • Sub-Investigator:
          • Könül Pashayeva, Dr.
        • Sub-Investigator:
          • Katharina Lisenko, Dr.
        • Sub-Investigator:
          • Johann W. Schmier, Dr.
      • Homburg, Germany, 66421
        • Recruiting
        • Universitätsklinikum des Saarlandes, Klinik f. Innere Medizin I Hämatologie & Onkologie
        • Principal Investigator:
          • Michael Pfreundschuh, Prof.
        • Sub-Investigator:
          • Jörg Bittenbring, Dr.
      • Idar-Oberstein, Germany, 55743
        • Recruiting
        • Klinikum Idar-Oberstein GmbH, Medizinische Klinik I
        • Sub-Investigator:
          • Eva Roemer, Dr.
        • Sub-Investigator:
          • Marina Bischoff, Dr.
        • Sub-Investigator:
          • Maritza Lar-Valverde, Dr.
        • Principal Investigator:
          • Johannes Schneider, Dr.
      • Jena, Germany, 07747
        • Recruiting
        • Universitätsmedizin Jena, Klinik f. Innere Medizin II, Abteilung Hämatologie u. Internistische Onkologie
        • Principal Investigator:
          • Sebastian Scholl, PD Dr.
        • Sub-Investigator:
          • Thomas Ernst, PD Dr.
      • Karlsruhe, Germany, 76133
        • Recruiting
        • Städtisches Klinikum Karlsruhe, Med. Klinik III, Hämatologie und Onkologie
        • Principal Investigator:
          • Martin Bentz, Prof.
        • Sub-Investigator:
          • Joy Dickinson, Dr.
      • Kiel, Germany, 24105
        • Recruiting
        • Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik f. Innere Medizin II - Hämatologie und Onkologie
        • Principal Investigator:
          • Christiane Pott, Prof. Dr.
        • Sub-Investigator:
          • Michael Kneba, Prof. Dr.
        • Sub-Investigator:
          • Sebastian Böttcher, PD Dr.
        • Sub-Investigator:
          • Matthias Ritgen, Dr.
      • Koblenz, Germany, 56068
        • Recruiting
        • Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Klinik f. Innere Medizin
        • Principal Investigator:
          • Dirk Niemann, Dr.
        • Sub-Investigator:
          • Ralph Naumann, Prof.
        • Sub-Investigator:
          • Christian Breitbarth-Girmscheid, Dr.
        • Sub-Investigator:
          • Elisabeth Fritz, Dr.
      • Koblenz, Germany, 56068
        • Recruiting
        • Praxisklinik f. Hämatologie und Onkologie Koblenz
        • Principal Investigator:
          • Jörg Thomalla, Dr.
        • Sub-Investigator:
          • Christoph von Roye, Dr.
        • Sub-Investigator:
          • Rudolf Weide, Prof. Dr.
        • Sub-Investigator:
          • Geothy Chakupurakal, Dr.
        • Sub-Investigator:
          • Jochen Heymanns, Dr.
        • Sub-Investigator:
          • Florence Klose, Dr.
      • Köln, Germany, 50937
        • Recruiting
        • Uniklinik Köln, Klinik I für Innere Medizin
        • Principal Investigator:
          • Kai Hübel, Prof.
        • Sub-Investigator:
          • Peter Borchmann, Prof.
        • Sub-Investigator:
          • Bastian von Tresckow, Dr.
        • Sub-Investigator:
          • Christian Pallasch, Dr.
        • Sub-Investigator:
          • Armin Tuchscherer, Dr.
        • Sub-Investigator:
          • Thomas Zander, PD Dr.
        • Sub-Investigator:
          • Stephanie Sasse, Dr.
      • Landshut, Germany, 84028
        • Recruiting
        • Onkologisch-Hämatologische Praxis Dr. Vehling-Kaiser
        • Principal Investigator:
          • Ursula Vehling-Kaiser, Dr.
        • Sub-Investigator:
          • Mike Haberkorn
        • Sub-Investigator:
          • Chrysantha Langer, Dr.
        • Sub-Investigator:
          • Franziskus Finsterwalder, Dr.
        • Sub-Investigator:
          • Michael Sohm, Dr.
      • Landshut, Germany, 84034
        • Recruiting
        • Klinikum Landshut gGmbH, Med. Klinik III, Hämatologie/Internistische Onkologie
        • Principal Investigator:
          • Barbara Kempf
        • Sub-Investigator:
          • Heiko Merkle, Dr.
        • Sub-Investigator:
          • Gabriela Totok, Dr.
        • Sub-Investigator:
          • Adrian Schembor
      • Lebach, Germany, 66822
        • Recruiting
        • Caritas-KHLebach, Gemeinschaftspraxis f. Hämatologie und Onkologie, Onkologisches Zentrum Lebach
        • Principal Investigator:
          • Stephan Kremers, Dr.
        • Sub-Investigator:
          • Stefan Bauer, PD Dr.
        • Sub-Investigator:
          • Alessandro Falgiatore, Dr.
        • Sub-Investigator:
          • Celine Szysnik, Dr.
        • Sub-Investigator:
          • Hauke Täger, Dr.
      • Leipzig, Germany, 04103
        • Recruiting
        • Universitätsklinikum Leipzig AöR, selbständige Abteilung f. Hämatologie und Internistische Onkologie, Hämostaseologische Ambulanz
        • Principal Investigator:
          • Dietger Niederwieser, Prof.
        • Sub-Investigator:
          • Gerhard Behre, Prof. Dr.
        • Sub-Investigator:
          • Vladan Vucinic, Dr.
        • Sub-Investigator:
          • Song-Yau Wang, Dr.
        • Sub-Investigator:
          • Sebastian Schwind
        • Sub-Investigator:
          • Christine Döhring
      • Lemgo, Germany, 32657
        • Recruiting
        • Klinikum Lippe GmbH, Onkologie und Hämatologie
        • Principal Investigator:
          • Frank Hartmann, Prof. Dr.
        • Sub-Investigator:
          • Tanja Hesse, Dr.
        • Sub-Investigator:
          • Susanne Horstmeyer, Dr.
      • Ludwigshafen, Germany, 67063
        • Recruiting
        • Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Med. Klinik A
        • Principal Investigator:
          • Martin Hoffmann, Dr.
        • Sub-Investigator:
          • Michael Uppenkamp, Prof.
      • Magdeburg, Germany, 39120
        • Recruiting
        • Universitätsklinikum Magdeburg AöR, Klinik f. Hämatologie und Onkologie
        • Principal Investigator:
          • Enrico Schalk, Dr.
        • Sub-Investigator:
          • Christian Krogel, Dr.
        • Sub-Investigator:
          • Denise Wolleschak, Dr.
      • Mainz, Germany, 55131
        • Recruiting
        • Universitätsmedizin der Univ. Mainz, III. Med. Klinik u. Poliklinik
        • Principal Investigator:
          • Georg Heß, PD Dr.
        • Sub-Investigator:
          • Hans-Joachim Beck, Dr.
        • Sub-Investigator:
          • Eva-Maria Wagner, Dr.
        • Sub-Investigator:
          • Oliver Kriege
      • Minden, Germany, 32429
        • Recruiting
        • Johannes Wiesling Klinikum Minden, Klinik f. Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin
        • Principal Investigator:
          • Hans-Heinrich Wöltjen, Dr.
        • Sub-Investigator:
          • Kai Wille, Dr.
        • Sub-Investigator:
          • Philip Dargatz, Dr.
      • München, Germany, 81377
        • Recruiting
        • Klinikum der Universität München, Med. Klinik und Poliklinik III
        • Contact:
        • Principal Investigator:
          • Martin Dreyling, Prof.
        • Sub-Investigator:
          • Christian Schmidt, Dr.
      • München, Germany, 81675
        • Recruiting
        • Klinikum Rechts der Isar, III. Med. Klinik - Hämatologie und Onkologie
        • Principal Investigator:
          • Ulrich Keller, Prof.
        • Sub-Investigator:
          • Christian Bogner, Dr.
        • Sub-Investigator:
          • Irina Kerle, Dr.
      • Münster, Germany, 48149
        • Recruiting
        • Universitätsklinikum Münster, Med. Klinik A, Translationale Onkologie / Lymphome
        • Principal Investigator:
          • Georg Lenz, Prof.
        • Sub-Investigator:
          • Christoph Schliemann, PD Dr.
        • Sub-Investigator:
          • Andrea Kerkhoff, Dr.
        • Sub-Investigator:
          • Arik Schulze, Dr.
        • Sub-Investigator:
          • Julia Reusch, Dr.
        • Sub-Investigator:
          • Ursula Stalmann
      • Nürnberg, Germany, 90419
        • Recruiting
        • Klinikum Nürnberg,5. Medizinische Klinik, Onkologie / Hämatologie
        • Principal Investigator:
          • Kerstin Schäfer-Eckart, Dr.
        • Sub-Investigator:
          • Knut Wendelin, Dr.
        • Sub-Investigator:
          • Josef Birkmann, PD Dr.
      • Oldenburg, Germany, 26133
        • Recruiting
        • Klinikum Oldenburg gGmbH, Med. Klinik II
        • Principal Investigator:
          • Bernd Metzner, PD Dr.
        • Sub-Investigator:
          • Ruth Thole, Dr.
        • Sub-Investigator:
          • Andreas Voß, Dr.
      • Potsdam, Germany, 14467
        • Recruiting
        • Klinikum Ernst von Bergmann Potsdam gGmbH, Zentrum f. Innere Medizin, Klinik f. Hämatologie und Onkologie
        • Principal Investigator:
          • Georg Maschmeyer-Krull, Prof.
        • Sub-Investigator:
          • Frank Breywisch, Dr,
      • Regensburg, Germany, 93049
        • Recruiting
        • KH Barmherzige Brüder, Klinik f. Onkologie und Hämatologie
        • Principal Investigator:
          • Bernhard Heilmeier, Dr.
        • Sub-Investigator:
          • Anke Schlenska-Lange, Dr.
        • Sub-Investigator:
          • Veronika Berberich, Dr.
        • Sub-Investigator:
          • Jan Braess, Prof. Dr.
        • Sub-Investigator:
          • Nicolas Moosmann, Dr.
      • Rostock, Germany, 18057
        • Recruiting
        • Universitätsmedizin Rostock, Abt. f. Hämatologie und Onkologie, Klinik und Poliklinik für Innere Medizin
        • Principal Investigator:
          • Christian Junghanß, Prof.
        • Sub-Investigator:
          • Christina Große-Thie, Dr.
        • Sub-Investigator:
          • Larissa Henze, Dr.
        • Sub-Investigator:
          • Brigitte Kragl, Dr.
      • Stuttgart, Germany, 70174
        • Recruiting
        • Klinikum Stuttgart - Katharinenhospital, Klinik f. Hämatologie und Onkologie
        • Principal Investigator:
          • Gerald Illerhaus, Prof.
        • Sub-Investigator:
          • Dennis Hahn, Dr.
        • Sub-Investigator:
          • Philippe Nono, Dr.
        • Sub-Investigator:
          • Kristina Hadler-Mikesch, Dr.
      • Stuttgart, Germany, 70376
        • Recruiting
        • Robert-Bosch-Krankenhaus, Abt.f. Hämatologie und Onkologie
        • Principal Investigator:
          • Matthias Vöhringer, Dr.
        • Sub-Investigator:
          • Sonja Martin, Dr.
        • Sub-Investigator:
          • Liza Bacchus, Dr.
      • Traunstein, Germany, 83278
        • Recruiting
        • Klinikum Traunstein, Hämatologie - Onkologie- Palliativmedizin
        • Principal Investigator:
          • Thomas W. Kubin, Dr.
        • Sub-Investigator:
          • Florian Zettl, Dr.
        • Sub-Investigator:
          • Elke Hagenreiner, Dr.
        • Sub-Investigator:
          • Elisabeth Dietl, Dr.
        • Sub-Investigator:
          • Klaus Eberl, Dr.
      • Trier, Germany, 54290
        • Recruiting
        • Klinikum Mutterhaus der Borromäerinnen gGmbH, Okologisches Zentrum
        • Principal Investigator:
          • Rolf Mahlberg, Dr.
        • Sub-Investigator:
          • Stefan Heidel, Dr.
      • Tübingen, Germany, 72026
        • Recruiting
        • Universitätsklinikum Tübingen, Med Klinik I, Innere Medizin II
        • Principal Investigator:
          • Martin Sökler, Dr.
        • Sub-Investigator:
          • Martin Müller, PD Dr.
      • Ulm, Germany, 89081
        • Recruiting
        • Universitätsklinikum Ulm, Klinik für Innere Medizin III
        • Principal Investigator:
          • Stephan Stilgenbauer, Prof.
        • Sub-Investigator:
          • Johannes Bloehdorn, Dr.
      • Wolfsburg, Germany, 38440
        • Recruiting
        • Klinikum Wolfsburg, Med. Klinik II
        • Principal Investigator:
          • Steffen Neumann, Dr.
        • Sub-Investigator:
          • Nils Homann, Prof.
      • Würzburg, Germany, 97080
        • Not yet recruiting
        • Universitätsklinikum Würzburg, Med. Klinik u. Poliklinik II /ZIM
        • Principal Investigator:
          • Max S. Topp, Prof.
        • Sub-Investigator:
          • Johannes Düll, Dr.
  • Italy
      • Alessandria, Italy, 15121
        • Recruiting
        • Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo, SC Ematologia
        • Principal Investigator:
          • Marco Ladetto, Dr.
        • Sub-Investigator:
          • Manuela Zanni, Dr.
        • Sub-Investigator:
          • Anna Baraldi, Dr.
        • Sub-Investigator:
          • Federico Monaco, Dr.
      • Bologna, Italy, 40138
        • Not yet recruiting
        • Policlinico S. Orsola Malpighi, Istituto di Ematologia e Oncologia Medica Seragnoli
        • Principal Investigator:
          • Vittorio Stefoni, Dr.
      • Bolzano, Italy, 39100
        • Not yet recruiting
        • Comprensorio Sanitario di Bolzano, Ematologia e trapianto di midollo osseo
        • Principal Investigator:
          • Michael Mian, Dr.
      • Brescia, Italy, 25123
        • Not yet recruiting
        • Spedali Civili, Struttura Complessa di Ematologia
        • Principal Investigator:
          • Alessandro Re, Dr.
      • Cagliari, Italy, 09121
        • Not yet recruiting
        • Ospedale Businco, UO Ematologia - CTMO
        • Principal Investigator:
          • Maria Giuseppina Cabras, Dr.
      • Cuneo, Italy, 12100
        • Not yet recruiting
        • ASO S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
        • Principal Investigator:
          • Claudia Castellino, Dr.
      • Firenze, Italy, 50134
        • Not yet recruiting
        • AOU Policlinico Careggi, Unità Funzionale di Ematologia
        • Principal Investigator:
          • Luigi Rigacci, Dr.
      • Genova, Italy, 16132
        • Not yet recruiting
        • IRCCS AOU S. Martino - IST, Clinica Ematologia
        • Principal Investigator:
          • Marco Gobbi, Prof.
      • Genova, Italy, 16132
        • Not yet recruiting
        • IRCCS AOU S. Martino - IST, Ematologia
        • Principal Investigator:
          • Angela Congiu, Dr.
      • Meldola (FC), Italy, 47014
        • Not yet recruiting
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Ematologia
        • Principal Investigator:
          • Gerardo Musuraca, Dr.
      • Milano, Italy, 20132
        • Not yet recruiting
        • Istituto Scientifico San Raffaele, Unità Ricerca Clinica Linfomi
        • Principal Investigator:
          • Andres Ferreri, Dr.
      • Milano, Italy, 20162
        • Not yet recruiting
        • Ospedale Niguarda, Struttura Complessa di Ematologia
        • Principal Investigator:
          • Chiara Rusconi, Dr.
      • Modena, Italy, 41124
        • Not yet recruiting
        • Università di Modena e Reggio Emilia Policlinico - COM Centro Oncologico Modenese, Dipartimento di Oncologia ed Ematologia
        • Principal Investigator:
          • Franco Narni, Prof.
      • Monza, Italy, 20052
        • Not yet recruiting
        • Ospedale S. Gerardo, Divisione di Ematologia
        • Principal Investigator:
          • Silvia Bolis, Dr.
      • Napoli, Italy, 80131
        • Recruiting
        • "IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale", Ematologia Oncologica
        • Principal Investigator:
          • Antonello Pinto, Dr.
      • Novara, Italy, 28100
        • Not yet recruiting
        • AOU Maggiore della Carità - Università del Piemonte Orientale, S.C.D.U Ematologia
        • Principal Investigator:
          • Gianluca Gaidano, Prof.
      • Palermo, Italy, 90146
        • Not yet recruiting
        • AO Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
        • Principal Investigator:
          • Caterina Patti, Dr.
      • Pavia, Italy, 27100
        • Not yet recruiting
        • IRCCS Fondazione Policlinico San Matteo, Clinica Ematologia
        • Principal Investigator:
          • Luca Arcaini, Prof.
      • Pisa, Italy, 56126
        • Not yet recruiting
        • Azienda Ospedaliera Pisana Ospedale "S.Chiara", Dipartimento di Oncologia Divisione di Ematologia
      • Ravenna, Italy, 48121
        • Not yet recruiting
        • Ospedale S. Maria delle Croci, U.O di Ematologia
        • Principal Investigator:
          • Monica Tani, Dr.
      • Reggio Calabria, Italy, 89125
        • Not yet recruiting
        • Azienda Ospedaliera Bianchi, Melacrino, Morelli, Divisione di Ematologia
        • Principal Investigator:
          • Caterina Stelitano, Dr.
      • Reggio Emilia, Italy, 42123
        • Not yet recruiting
        • Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Ematologia
        • Principal Investigator:
          • Francesco Merli, Dr.
      • Rimini, Italy, 47923
        • Not yet recruiting
        • Ospedale degli Infermi, U.O. Ematologia
        • Principal Investigator:
          • Annalia Molinari, Dr.
      • Roma, Italy, 00133
        • Not yet recruiting
        • Policlinico Tor Vergata, UOC Oncoematologia
        • Principal Investigator:
          • Maria Cantonetti, Prof
      • Roma, Italy, 00161
        • Not yet recruiting
        • Università La Sapienza, Ematologia
        • Principal Investigator:
          • Maurizio Martelli, Prof.
      • San Giovanni Rotondo, Italy, 71013
        • Not yet recruiting
        • Casa Sollievo della Sofferenza, U.O. Ematologia
        • Principal Investigator:
          • Nicola Cascavilla, Dr.
      • Torino, Italy, 10126
        • Not yet recruiting
        • A.O. Città della Salute e della Scienza, SC Ematologia
        • Principal Investigator:
          • Umberto Vitolo, Dr.
      • Torino, Italy, 10126
        • Not yet recruiting
        • A.O. U. Città della Salute e della Scienza, S C Ematologia U
        • Principal Investigator:
          • Federica Cavallo, Dr.
      • Treviso, Italy, 31100
        • Not yet recruiting
        • Ospedale Cà Foncello, U.O.C. Ematologia
        • Principal Investigator:
          • Piero Maria Stefani, Dr.
      • Tricase, Italy, 73054
        • Not yet recruiting
        • Ospedale Cardinale Panico, Divisione di Ematologia
        • Principal Investigator:
          • Vincenzo Pavone, Dr.
      • Udine, Italy, 33100
        • Not yet recruiting
        • ASUI Integrata di Udine, Clinica Ematologia
        • Principal Investigator:
          • Francesco Zaja, Prof.
      • Verona, Italy, 37134
        • Recruiting
        • Ospedale Policlinico G.B. Rossi, "Centro trapianto midollo osseo Ematologia"
        • Principal Investigator:
          • Fabio Benedetti, Dr.
      • Vicenza, Italy, 36100
        • Recruiting
        • Ospedale S. Bortolo, Ematologia
        • Principal Investigator:
          • Carlo Visco, Dr.
        • Sub-Investigator:
          • Maria Chiara Tisi, Dr.
        • Sub-Investigator:
          • Omar Perbellini, Dr.
  • Norway
      • Bergen, Norway, 5021
        • Not yet recruiting
        • Haukeland University Hospital , Dept. of Oncology and Medical Physics
        • Principal Investigator:
          • Anne Turid Bjørnevik, Dr.
      • Oslo, Norway, 0310
        • Not yet recruiting
        • Oslo University Hospital, Dept of Oncology
        • Principal Investigator:
          • Arne Kolstad, Dr.
      • Stavanger, Norway, 4011
        • Not yet recruiting
        • Stavanger University Hospital, Division for Hematology&Oncology
        • Principal Investigator:
          • Peter Meyer, Dr.
      • Tromsø, Norway, 9038
        • Not yet recruiting
        • UNN Tromsø, Oncology Dep
        • Principal Investigator:
          • Fredrik Sund
      • Trondheim, Norway, 7006
        • Not yet recruiting
        • St. Olavs Hospital, Department of Oncology
        • Principal Investigator:
          • Karin Inger Martina Fahl Wader, MD Phd.
  • Sweden
      • Göteborg, Sweden, 413 45
        • Not yet recruiting
        • Sahlgrenska University Hospital, Section of Hematology and Coagulation, Dept of internal medicine
        • Principal Investigator:
          • Catharina Lewerin
      • Linköping, Sweden, 581 85
        • Recruiting
        • University Hospital, Dept of Hematolgy
        • Principal Investigator:
          • Ingemar Lagerlöf, Dr.
        • Sub-Investigator:
          • Ronald Svensson, Dr.
      • Lulea, Sweden, 971 80
        • Not yet recruiting
        • Sunderbyn Hospital, Dept of Medicine
        • Principal Investigator:
          • Lena Brandefors, Dr.
      • Lund, Sweden, 221 85
        • Recruiting
        • Skåne University Hospital
        • Contact:
          • Mats Jerkeman, MD
        • Principal Investigator:
          • Mats Jerkeman, MD
      • Stockholm, Sweden, 141 86
        • Recruiting
        • Karolinska University Hospital, Center of Hematology
        • Principal Investigator:
          • Kristina Sonnevi, Dr.
        • Sub-Investigator:
          • Torsten Dahlen, Dr.
        • Sub-Investigator:
          • Fredrik Celsing, Dr.
        • Sub-Investigator:
          • Maria Ljungqvist, Dr.
      • Umea, Sweden, 901 85
        • Not yet recruiting
        • Norrland University Hospital, Dept of Oncology
        • Principal Investigator:
          • Karin Papworth
        • Sub-Investigator:
          • Sara Sjöström, Dr.
      • Uppsala, Sweden, 751 85
        • Recruiting
        • Academic Hospital, Dept of Oncology
        • Principal Investigator:
          • Anna Laurell, Dr.
        • Sub-Investigator:
          • Ingrid Glimelius, Dr.
      • Örebro, Sweden, 701 85
        • Recruiting
        • Örebro University Hospital, Dept of Oncology
        • Principal Investigator:
          • Karin Nyström, Dr.
        • Sub-Investigator:
          • David Löfgren
        • Sub-Investigator:
          • Urban Jerlström

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

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

All patients must meet the following criteria:

  • Histologically confirmed diagnosis of MCL according to WHO classification
  • suitable for high-dose treatment including high-dose Ara-C
  • Stage II-IV (Ann Arbor)
  • Age ≥ 18 years and ≤ 65 years
  • Previously untreated MCL
  • At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
  • ECOG/WHO performance status ≤ 2

  • The following laboratory values at screening (unless related to MCL):

    • Absolute neutrophil count (ANC) ≥1000 cells/µL
    • Platelets ≥100,000 cells/µL
    • Transaminases (AST and ALT) ≤3 x upper limit of normal (ULN)
    • Total bilirubin ≤2 x ULN unless due to known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome])
    • Creatinine ≤2 mg/dL or calculated creatinine clearance ≥ 50 mL/min
  • Written informed consent form according to ICH/EU GCP and national regulations
  • Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug.

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from participating in the study.

  • Major surgery within 4 weeks prior to randomization.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg phenprocoumon).
  • History of stroke or intracranial hemorrhage within 6 months prior to randomization.
  • Requires treatment with strong CYP3A4/5 inhibitors.
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
  • Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.
  • Known CNS involvement of MCL
  • Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of ibrutinib itself or to the excipients in its formulation)
  • Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
  • Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon except prephase therapy according to trial protocol

  • Serious concomitant disease interfering with a regular therapy according to the study protocol:

    • Cardiac (Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below LLN )
    • Pulmonary (e.g. chronic lung disease with hypoxemia)
    • Endocrinological (e.g. severe, not sufficiently controlled diabetes mellitus)
    • Renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value and/or creatinin clearance < 50 ml/min)
    • Impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2,0 mg/dl unless due to morbus Meulengracht (Gilbert-Meulengracht-Syndrome)
  • Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test)
  • Prior organ, bone marrow or peripheral blood stem cell transplantation
  • Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer or in situ uterine cervix cancer
  • Pregnancy or lactation
  • Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
  • Subjects not able to give consent
  • Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial
  • Participation in another clinical trial within 30 days before randomization in this study.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Arm A

R-CHOP/R-DHAP: Alternating 3 cycles of R-CHOP in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle

Drug: R-CHOP/R-DHAP

ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM
Drug: R-CHOP/R-DHAP
Drug: R-CHOP/DHAP Alternating 3x R-CHOP (Rituximab , Cyclophosphamide ,Doxorubicine ,Vincristine , Prednisone) / 3x R-DHAP (Rituximab , Dexamethasone, Ara-C, Cisplatine, G-CSF)
Other Names:
  • rituximab, CHOP, DHAP
Drug: ASCT conditioning

ASCT conditioning THAM or BEAM, stratified per site before trial activation at site

THAM (TBI (total body irradiation), Ara-C, Melphalan) or

BEAM (BCNU, Etoposide, Cytarabine, Melphalan)

Other Names:
  • THAM or BEAM
Experimental: Experimental Arm A+I

R-CHOP+Ibrutinib/R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days 1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle

Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction)

ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM

2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenace)
Drug: R-CHOP/R-DHAP
Drug: R-CHOP/DHAP Alternating 3x R-CHOP (Rituximab , Cyclophosphamide ,Doxorubicine ,Vincristine , Prednisone) / 3x R-DHAP (Rituximab , Dexamethasone, Ara-C, Cisplatine, G-CSF)
Other Names:
  • rituximab, CHOP, DHAP
Drug: ASCT conditioning

ASCT conditioning THAM or BEAM, stratified per site before trial activation at site

THAM (TBI (total body irradiation), Ara-C, Melphalan) or

BEAM (BCNU, Etoposide, Cytarabine, Melphalan)

Other Names:
  • THAM or BEAM
Drug: Ibrutinib (Induction)
Ibrutinib: only in cycle 1,3,5 on Day 1-19
Other Names:
  • Imbruvica
Drug: Ibrutinib (Maintenance)
Ibrutinib (Maintenance), daily 560 mg for 2 years;
Other Names:
  • Imbruvica
Experimental: Experimental Arm I

R-CHOP+Ibrutinib / R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle

Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction)

2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenance)
Drug: R-CHOP/R-DHAP
Drug: R-CHOP/DHAP Alternating 3x R-CHOP (Rituximab , Cyclophosphamide ,Doxorubicine ,Vincristine , Prednisone) / 3x R-DHAP (Rituximab , Dexamethasone, Ara-C, Cisplatine, G-CSF)
Other Names:
  • rituximab, CHOP, DHAP
Drug: Ibrutinib (Induction)
Ibrutinib: only in cycle 1,3,5 on Day 1-19
Other Names:
  • Imbruvica
Drug: Ibrutinib (Maintenance)
Ibrutinib (Maintenance), daily 560 mg for 2 years;
Other Names:
  • Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Failure Free Survival
Time Frame: From start of treatment until stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause, whichever comes first, assessed up to 120 months.
From start of treatment until stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause, whichever comes first, assessed up to 120 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From start of treatment until the date of first documented progression, assessed up to 120 months.
From start of treatment until the date of first documented progression, assessed up to 120 months.
Number of participants with treatment-related adverse events as assessed by CTC Version 4.03
Time Frame: From start of Ibrutinib treatment during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints. Through study conduction, an average of up to 30 months.
Safety and tolerability
From start of Ibrutinib treatment during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints. Through study conduction, an average of up to 30 months.
Progression-free survival (PFS)
Time Frame: PFS is the time to progression or death from any cause. Assed up to 120 months.
PFS is the time to progression or death from any cause. Assed up to 120 months.
Number of Secondary Primary Malignancies
Time Frame: From start of treatment through the study conduction, up to 120 months.
Toxicity Endpoints
From start of treatment through the study conduction, up to 120 months.
Number of Adverse Events by CTC grade (Version 4.03)
Time Frame: From start of treatment through the study conduction, up to 120 months.
Toxicity Endpoints
From start of treatment through the study conduction, up to 120 months.

Collaborators and Investigators

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

Sponsor

Prof. Dr. M. Dreyling (co-chairman)

Collaborators

LMU Klinikum

Investigators

  • Principal Investigator: Martin Dreyling, Prof., Klinikum der Universität München

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

July 1, 2016

Primary Completion (Anticipated)

May 1, 2021

Study Completion (Anticipated)

May 1, 2026

Study Registration Dates

First Submitted

July 14, 2016

First Submitted That Met QC Criteria

August 3, 2016

First Posted (Estimate)

August 8, 2016

Study Record Updates

Last Update Posted (Actual)

December 19, 2017

Last Update Submitted That Met QC Criteria

December 17, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRIANGLE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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