Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma

2-Weekly CHOP Chemotherapy With Dose-Dense Rituximab for the Treatment of Patients Aged 61 to 80 Years With Aggressive CD-20 Positive B-Cell Lymphomas: A Phase-II/Pharmacokinetic Study (CHOP-R-ESC)

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with previously untreated B-cell lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclophosphamide; Other: pharmacological study; Radiation: radiation therapy; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: rituximab; Biological: pegfilgrastim

Detailed Description

OBJECTIVES:

Primary

• Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive B-cell lymphoma.
• To determine whether increased single-doses of rituximab for males can compensate their lower serum levels.
• Evaluate the safety and toxicity profile of this regimen in male patients.

Secondary

• Determine the rate of complete responses, primary progressions under therapy, event-free survival, progression-free survival, and overall survival in patients treated with this regimen.
• Determine the rate of primary progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. All patients undergo the following treatment.

• Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral prednisone on days -6 to 0.
• Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy proceed to salvage chemotherapy off study.

Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4 weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy proceed to salvage chemotherapy off study.

Patients are then stratified according to center, International Prognostic Index (1-2 vs 3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.

• Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
• Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.

Some patients undergo blood sample collection periodically during and after treatment for pharmacokinetic studies.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year therafter.

• Study Type: Interventional
• Enrollment (Actual): 586
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, CZ-662 63
    • University Hospital Brno
  • Prague 5, Czechia, CZ-150 06
    • Charles University Hospital
• France
  • Lyon, France, 69322
    • Hopital Debrousse
• Germany
  • Aachen, Germany, 52070
    • Haematologisch Onkologische Praxis
  • Aalen, Germany, D-73430
    • Ostalb-Klinikum Aalen
  • Amberg, Germany, D-92224
    • Klinikum St. Marien
  • Ansbach, Germany, 91522
    • Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
  • Aschaffenburg, Germany, RG 63739
    • II. Medizinische Klinik
  • Aschaffenburg, Germany, 63739
    • Specialist Practice for Oncology
  • Augsburg, Germany, DOH-86156
    • Klinikum Augsburg
  • Augsburg, Germany, 86150
    • Haematologische Praxis
  • Augsburg, Germany, 86150
    • Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
  • Aurich, Germany, 26603
    • Kreiskrankenhaus Aurich
  • Bad Hersfeld, Germany, 36251
    • Regional Hospital Bad Hersfeld
  • Bad Saarow, Germany, 15526
    • HELIOS Klinikum Bad Saarow
  • Bad Salzuflen, Germany, 32105
    • Internistische Praxis - Bad Salzuflen
  • Bad Soden, Germany, 65812
    • Onkologische Schwerpunktpraxis und Tagesklinik Dres
  • Bad Säckingen, Germany, 79704
    • Kreiskrankenhaus Bad Saeckingen
  • Bad Urach, Germany, D-72574
    • Ermstalklinik Bad Urach
  • Bamberg, Germany, 96049
    • Klinikum am Bamberg
  • Bayreuth, Germany, D-95445
    • Klinikum Bayreuth
  • Bayreuth, Germany, 95445
    • Krankenhaus Hohe Warte Mediziniche Klinik
  • Bergisch Gladbach, Germany, D-51429
    • Praxis Dr. med. Stefan Korsten
  • Berlin, Germany, D-10117
    • Charité - Campus Charité Mitte
  • Berlin, Germany, D-12200
    • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Berlin, Germany, 13347
    • Internistische Gemeinschaftspraxis - Berlin
  • Berlin, Germany, 13357
    • Haematologisch-Onkologische Schwerpunktpraxis
  • Berlin, Germany, 14195
    • Internistische Gemeinschaftspraxis - Berlin
  • Berlin, Germany, 13589
    • Evang. Waldkrankenhaus Spandau
  • Berlin, Germany, D-13125
    • Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
  • Berlin, Germany, D-10559
    • Onkolog - Haematolog Schwerpunktpraxis
  • Berlin, Germany, 10249
    • Onkologisches Versorgungszentrum Friedrichshain
  • Berlin, Germany, 12559
    • DRK Kliniken Berlin - Koepenick
  • Berlin, Germany, D-12351
    • Vivantes Klinikum Neukoelln
  • Bernburg, Germany, 06406
    • Hospital Complex Bernburg
  • Bielefeld, Germany, D-33615
    • Franziskus Hospital
  • Bietigheim, Germany, 74319
    • Krankenhaus Bietigheim
  • Bocholt, Germany, DOH-463974290
    • Saint Agnes Hospital
  • Bochum, Germany, D-44791
    • Augusta-Kranken-Anstalt gGmbH
  • Bochum, Germany, D-44791
    • St. Josef-Hospital - Bochum
  • Bochum, Germany, D-44892
    • Knappschaftskrankenhaus Bochum-Langendreer
  • Bonn, Germany, D-53105
    • Universitaetsklinikum Bonn
  • Bonn, Germany, 53113
    • Johanniter-Krankenhaus Bonn
  • Bonn, Germany, D-53111
    • Medizinische Poliklinik
  • Borken, Germany, 46325
    • Praxis fuer Haematologie und Internistische Onkologie - Borken
  • Bottrop, Germany, D-46242
    • Knappschaftskrankenhaus Bottrop
  • Brandenburg, Germany, 14770
    • Hamatologische Sprechstunde
  • Braunschweig, Germany, G-38114
    • Staedtisches Klinikum Braunschweig
  • Bremen, Germany, D-28205
    • Klinikum Bremen-Mitte
  • Bremen, Germany, D-28239
    • DIAKO Ev. Diakonie Krankenhaus gGmbH
  • Bremen, Germany, 28209
    • Praxis Dres. F.& G. Doering
  • Bremerhaven, Germany, D-27568
    • St. Joseph Hospital
  • Bremerhaven, Germany, N 27574
    • Zentralkrankenhaus
  • Burgwedel, Germany, 30938
    • Praxis fuer Haematologie und Onkologie - Burgwedel
  • Bünde, Germany, 32257
    • Medizinische Klinik Am Lukas - Krankenhaus
  • Celle, Germany, D-29221
    • Onkologische Schwerpunktpraxis Celle
  • Celle, Germany, 29223
    • General Hospital
  • Chemnitz, Germany, D-09113
    • Hospital Kuchwald Chemnitz
  • Coburg, Germany, 96450
    • Klinikum Coburg
  • Coesfeld, Germany, 48653
    • Internistische Praxis - Coesfeld
  • Cologne, Germany, D-50677
    • Praxis Fuer Haematologie Internistische Onkologie
  • Cologne, Germany, D-50924
    • Medizinische Universitaetsklinik I at the University of Cologne
  • Cologne, Germany, 50674
    • Praxis Internistischer Onkologie und Haematologie - Koeln
  • Cologne, Germany, 51067
    • Kliniken der Stadt Koeln gGmbH - Krankenhaus Holweide
  • Cologne, Germany, 51105
    • Praxis fuer Onkologie - Kalk
  • Cologne-Merheim, Germany, D-51109
    • Lung Clinic Cologne-Merheim
  • Cottbus, Germany, D-03048
    • Carl - Thiem - Klinkum Cottbus
  • Damme, Germany, D-49401
    • Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke
  • Darmstadt, Germany, D-64283
    • Klinikum Darmstadt
  • Dessau, Germany, 06822
    • Staedtisches Klinikum Dessau
  • Detmold, Germany, 32756
    • Internistische Praxis
  • Dortmund, Germany, D-44137
    • Klinikum Dortmund
  • Dortmund, Germany, 44137
    • Saint Johannes Hospital Dortmund
  • Dresden, Germany, D-01307
    • Universitätsklinikum Carl Gustav Carus
  • Duesseldorf, Germany, D-40225
    • Universitaetsklinikum Duesseldorf
  • Duisburg, Germany, D-47166
    • St. Johannes Hospital - Medical Klinik II
  • Duisburg, Germany, 47228
    • Johanniter-Krankenhaus Rheinhausen GmbH
  • Dulmen, Germany, 48249
    • Franz Hospital Dulmen
  • Dusseldorf, Germany, 40489
    • Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth
  • Eberswalde, Germany, 16225
    • Klinikum Barnim GmbH, Werner Forssmann Krankenhaus
  • Ellwangen, Germany, 73479
    • Virngrund-Klinik Ellwangen
  • Emden, Germany, 26721
    • Hans - Susemihl - Krankenhaus
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Erlangen, Germany, D-91054
    • Medizinische Klinik III - Universitaetsklinikum Erlangen
  • Eschweiler, Germany, DOH-52249
    • St. Antonius Hospital
  • Essen, Germany, D-45122
    • Universitaetsklinikum Essen
  • Essen, Germany, D-45239
    • Evangelisches Krankenhaus Essen Werden
  • Esslingen, Germany, D-73730
    • Staedtische Kliniken Esslingen
  • Flensburg, Germany, 24939
    • Schwerpunktpraxis fuer Haematologie und Onkologie - Flensburg
  • Frankenthal, Germany, 67227
    • Gemeinschaftspraxis fuer Internistische - Frankenthal
  • Frankfurt, Germany, D-60590
    • Klinikum der J.W. Goethe Universitaet
  • Frankfurt, Germany, D-60488
    • Krankenhaus Nordwest
  • Frankfurt, Germany, D-60389
    • Onkologie Bethanien
  • Frankfurt (Oder), Germany, D-15236
    • Klinikum Frankfurt (Oder) GmbH
  • Frankfurt am Main, Germany, 60318
    • St. Marienkrankenhaus - Frankfurt am Main
  • Frechen, Germany, 50226
    • Praxis Internistischer Onkologie und Haematologie - Frechen
  • Freiburg, Germany, D-79106
    • Universitaetsklinikum Freiburg
  • Freiburg, Germany, 79098
    • Gemeinschaftspraxis - Freiburg
  • Freiburg, Germany, 79110
    • Evang. Deaconess Hospital Freiburg
  • Freiburg, Germany, D-79106
    • Praxis fur Interdisziplinaere Onkologie
  • Fulda, Germany, 36043
    • Municipal Hospital Complex
  • Garmisch-Partenkirchen, Germany, D-82467
    • Klinikum Garmisch - Partenkirchen GmbH
  • Gehrden, Germany, 30989
    • Robert - Koch Hospital
  • Gelsenkirchen, Germany, D-45899
    • Saint Josef Hospital
  • Germering, Germany, 82110
    • Internistische Praxisgemeinschaft
  • Giessen, Germany, 35392
    • Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
  • Giessen, Germany, 35392
    • Centre for Internal Medicine Gießen
  • Goch, Germany, D-47574
    • Wilhelm-Anton-Hospital gGmbH, Goch
  • Goslar, Germany, 38642
    • DR Herbert - Nieper Krankenhaus Goslar
  • Greifswald, Germany, 17487
    • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
  • Gummersbach, Germany, D-51643
    • Kreiskrankenhaus Gummersbach GmbH
  • Gustrow, Germany, 18273
    • Internistisch-Haematologische Gemeinschaftspraxis - Gustrow
  • Görlitz, Germany, 02828
    • Staedtisches Klinikum Görlitz GmbH
  • Göttingen, Germany, D-37075
    • Universitaetsklinikum Göttingen
  • Gütersloh, Germany, D-33332
    • Staedtisches Klinikum Gütersloh
  • Hagen, Germany, D-58095
    • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
  • Hagen, Germany, D-58095
    • Allgemeines Krankenhaus Hagen
  • Halberstadt, Germany, D 38820
    • St. Salvator Krankenhaus
  • Halle, Germany, D-06120
    • Krankenhaus Martha-Maria Halle-Doelau gGmbH
  • Halle, Germany, 06110
    • Internistische Gemeinschaftspraxis - Halle
  • Halle, Germany, D-06097
    • Universitaetsklinikum Halle
  • Halle, Germany, D-06110
    • Krankenhaus St. Elisabeth und St. Barbara
  • Haltern, Germany, D-45721
    • St. Sixtus Hospital
  • Hamburg, Germany, D-20246
    • University Medical Center Hamburg - Eppendorf
  • Hamburg, Germany, 22087
    • Marienkrankenhaus
  • Hamburg, Germany, D-20099
    • Asklepios Klinik St. Georg
  • Hamburg, Germany, D-22767
    • Haematologisch-Onkologische Praxis Altona
  • Hamburg, Germany, 22763
    • Allgemeines Krankenhaus Altona
  • Hamburg, Germany, 21029
    • Praxis fuer Innere Medizin - Bergedorf
  • Hamburg, Germany, D-20095
    • Onkologische Schwerpunktpraxis Dr. med. Verpoort, PD Dr. med. Zeller and Dr. med. Wierecky
  • Hamburg, Germany, D-22417
    • Asklepios Klinik Nord Heidberg
  • Hamm, Germany, 59065
    • St. Marien Hospital
  • Hamm, Germany, D-59063
    • Evangelische Krankenhaus Hamm
  • Hanau, Germany, 63450
    • Klinikum Stadt Hanau
  • Hannover, Germany, D-30625
    • Medizinische Hochschule Hannover
  • Hannover, Germany, D-30449
    • Krankenhaus Siloah - Medizinische Klinik II
  • Hannover, Germany, 30169
    • Schwerpunktpraxis Haematologie/Onkologie - Hannover
  • Hannover, Germany, D-30559
    • Henriettenstiftung Frauenklinik
  • Harrislee, Germany, D-24955
    • Oncology Specialists Clinic
  • Heidelberg, Germany, D-69126
    • Thoraxklinik Heidelberg
  • Heidelberg, Germany, D-69117
    • Ruprecht - Karls - Universitaet Heidelberg
  • Heidenheim, Germany, 89522
    • Regional Hospital Heidenheim
  • Heilbronn, Germany, 74177
    • Regional Hospital Am Plattenwald Bad Friedrichshall
  • Herford, Germany, D-32049
    • Klinikum Herford
  • Herne, Germany, D-44625
    • Marienhospital at Ruhr University Bochum
  • Herrsching Am Ammersee, Germany, D-82211
    • Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
  • Hildesheim, Germany, D-31134
    • St. Bernward Krankenhaus
  • Hildesheim, Germany, D-31134
    • Onkologische Schwerpunktpraxis
  • Hildesheim, Germany, D-31134
    • Staedtisches Krankenhaus Hildesheim
  • Holzminden, Germany, 37603
    • Evang. Hospital
  • Homberg, Germany, D-34576
    • Haematologie und Internistische Onkologie Praxis
  • Homburg, Germany, D-66424
    • Universitaetsklinikum des Saarlandes
  • Hoyerswerda, Germany, 02977
    • Hospital Complex Hoyerswerda
  • Idar-Oberstein, Germany, D-55743
    • Clinic for Bone Marrow Transplantation and Hematology and Oncology
  • Jena, Germany, 07743
    • Internistische Gemeinschaftspraxis - Jena
  • Jena, Germany, 07747
    • Klinikum der Friedrich-Schiller Universitaet Jena
  • Kaiserslautern, Germany, D-67653
    • Westpfalz-Klinikum GmbH
  • Kaiserslautern, Germany, 67655
    • Onkologische Gemeinschaftspraxis - Kaiserslautern
  • Karlsruhe, Germany, 76133
    • Staedtisches Klinikum Karlsruhe gGmbH
  • Karlsruhe, Germany, D-76137
    • St. Vincentius - Kliniken
  • Kassel, Germany, D-34117
    • Internistische Gemeinschaftspraxis - Kassel
  • Kassel, Germany, 34121
    • Red Cross Hospital Kassel
  • Kempten, Germany, D-87439
    • Klinikum Kempten Oberallgaeu
  • Kiel, Germany, 23116
    • Staedtisches Krankenhaus Kiel
  • Koblenz, Germany, D-56068
    • Praxis fuer Haematologie und Onkologie
  • Koblenz, Germany, D-56068
    • Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH
  • Kornwestheim, Germany, D-70806
    • Leonardis Clinic
  • Krefeld, Germany, D-47805
    • Klinikum Krefeld GmbH
  • Krefeld, Germany, 47798
    • Haematologische / Onkologische Schwerpunktpraxis
  • Kronach, Germany, 96317
    • Internistische Onkologische Praxis - Kronach
  • Kronach, Germany, D-96317
    • Frankenwald Klinik
  • Landshut, Germany, 84028
    • Internistische Praxis - Landshut
  • Landshut, Germany, 84034
    • Klinikum Landshut
  • Lebach, Germany, 66822
    • Caritas - Krakenhaus Lebach
  • Leer, Germany, D-26789
    • Onkologische Schwerpunktpraxis - Leer
  • Leipzig, Germany, 04179
    • Praxis fuer Onkologie am Diakonissenhaus
  • Leipzig, Germany, 04289
    • Forschungsgesellschaft mbH
  • Leipzig, Germany, 04289
    • Gemeinschaftspraxis fuer Dres. Aldaoud und Schwarzer
  • Leipzig, Germany, D-04103
    • University Leipzig Clinic of Internal Medicine
  • Leipzig, Germany, D-04129
    • Klinikum "St. Georg" Leipzig
  • Lemgo, Germany, D-32657
    • Klinikum Lippe - Lemgo
  • Limburg, Germany, D-65549
    • St. Vincenz Hospital Limburg
  • Lingen, Germany, D-49808
    • St. Bonifatius Hospital Lingen
  • Lippstadt, Germany, D-59555
    • Dreifaltigkeits Hospital
  • Loerrach, Germany, 79539
    • Kreiskrankenhaus Loerrach
  • Loerrach, Germany, D-79539
    • Onkologische Schwerpunktpraxis
  • Ludwigsburg, Germany, D-71640
    • Klinikum Ludwigsburg
  • Ludwigshafen, Germany, D-67067
    • St. Marien Hospital Ludwighafen
  • Ludwigshafen am Rhein, Germany, D-67063
    • Klinikum der Stadt Ludwigshafen am Rhein
  • Luebeck, Germany, D-23538
    • Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
  • Luebeck, Germany, D-23560
    • Sana Kliniken Luebeck
  • Luebeck, Germany, 23562
    • Schwerpunktpraxis fuer Haematologie und Onkologie - Luebeck
  • Luedenscheid, Germany, 58515
    • Kreiskrankenhaus Luedenscheid
  • Magdeburg, Germany, 39120
    • Universitatsklinikum der MA
  • Magdeburg, Germany, D-39002
    • Staedtisches Klinikum Magdeburg - Altstadt
  • Magdeburg, Germany, D-39104
    • Internistische Gemeinschaftspraxis - Magdeburg
  • Mainz, Germany, D-55101
    • Johannes Gutenberg University
  • Mainz, Germany, 55131
    • St. Vincenz und Elisabeth Hospital
  • Mannheim, Germany, D-68305
    • III Medizinische Klinik Mannheim
  • Mannheim, Germany, D-68161
    • Gemeinschaftspraxis
  • Marburg, Germany, D-35043
    • Universitaetsklinikum Giessen und Marburg GmbH - Marburg
  • Marburg, Germany, 35057
    • Schwerpunktpraxis Internist Onkologie - Marburg
  • Mayen, Germany, D-56727
    • Regional Hospital Mayen
  • Memmingen, Germany, 87700
    • Gemeinschaftspraxis Dres. med. Ellbrueck/Goeller/Kraenzle/Niedermeier/Jocham
  • Meppen, Germany, 49716
    • Krankenhaus Ludmillenstift
  • Minden, Germany, D-32423
    • Klinikum Minden
  • Minden, Germany, 32427
    • Gemeinschaftspraxis - Minden
  • Moenchengladbach, Germany, D-41063
    • Krankenhaus Maria Hilf GmbH
  • Moenchengladbach, Germany, D-41239
    • Haematologische Praxis - Moenchengladbach
  • Monchengladbach, Germany, D-41061
    • Ev. Hospital Bethesda
  • Muelheim An Der Ruhr, Germany, D-45468
    • St. Marien Hospital - Muelheim an der Ruhr
  • Muelheim an der Ruhr, Germany, 45466
    • Evangelisches Krankenhaus - Muelheim
  • Muenster, Germany, D-48149
    • Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster
  • Muenster, Germany, D-48149
    • Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
  • Muenster, Germany, 48145
    • Gemeinschaftspraxis - Muenster
  • Munich, Germany, D-81377
    • Klinikum der Universitaet Muenchen - Grosshadern Campus
  • Munich, Germany, 80804
    • Krankenhaus Muenchen Schwabing
  • Munich, Germany, D-81675
    • Klinikum Rechts der Isar - Technische Universitaet Muenchen
  • Munich, Germany, D-80335
    • Munich Oncologic Practice at Elisenhof
  • Munich, Germany, D-81545
    • Staedtisches Krankenhaus Muenchen - Harlaching
  • Munich, Germany, 80336
    • Universitaets - Kinderpoliklinik
  • Munich, Germany, D-81737
    • Municipal Hospital Munich
  • Mutlangen, Germany, D-73557
    • Klinikum Schwaebisch Gmuend Stauferklinik
  • Münchberg, Germany, D-95213
    • Kreiskrankenhaus Muenchberg
  • Nettetal, Germany, 41334
    • Staedtisches Krankenhaus Nettetal GmbH
  • Neubrandenburg, Germany, 17036
    • Klinikum Neubrandenburg
  • Neumarkt, Germany, D-92318
    • Onkologische Schwerwpunktpraxis Dr. Ladda
  • Neumarkt, Germany, D-92318
    • Regional Hospital Neumarkt
  • Neunkirchen, Germany, D-66538
    • Onkologische Schwerpunktpraxis Dr. Schmidt
  • Neunkirchen, Germany, D-66538
    • Staedtisches Klinikum Neunkirchen gGmbH
  • Neuss, Germany, 41460
    • Internistische Praxis - Neuss
  • Neuss, Germany, D-41464
    • Lukaskrankenhaus Neuss
  • Neuwied, Germany, 56564
    • DRK Krankenhaus Neuwied
  • Norderstedt, Germany, 22844
    • Praxis fuer Haematologie und Interne Onkologie
  • Nordhorn, Germany, 48527
    • Gemeinschaftspraxis fuer Onkologie - Nordhorn
  • Northeim, Germany, 37154
    • Gemeinschaftspraxis fuer Haematologie - Northeim
  • Nuremberg, Germany, D-90419
    • Klinikum Nuernberg - Klinikum Nord
  • Nuremberg, Germany, 90449
    • Praxisklinik fuer Innere Medizin - Nuernberg
  • Oberstaufen, Germany, D-87534
    • Schlossbergkliniken Oberstaufen
  • Offenbach, Germany, D-63065
    • Internistische Gemeinschaftspraxis - Offenbach
  • Offenburg, Germany, D-77654
    • Klinikum Offenburg
  • Oldenburg, Germany, D-26133
    • Klinikum Oldenburg
  • Oldenburg, Germany, 26121
    • Pius Hospital - Oldenburg
  • Oldenburg, Germany, D-26121
    • Internistische Gemeinschaftspraxis - Oldenburg
  • Oldenburg, Germany, D-26122
    • Ev. Hospital Oldenburg
  • Olpe, Germany, 57462
    • St. Martinus Hospital - Olpe
  • Osnabrück, Germany, D-49074
    • Marien Hospital
  • Osnabrück, Germany, D-49076
    • Klinikum Osnabrück GmbH
  • Osnabrück, Germany, D-49076
    • Paracelsus - Klinik Osnabrück
  • Paderborn, Germany, D-33098
    • Bruederkrankenhaus St. Josef Paderborn
  • Parchim, Germany, 19370
    • Asklepios Klinik - Parchim
  • Pforzheim, Germany, 75175
    • Staedtisches Krankenhaus
  • Pforzheim, Germany, 75179
    • Krankenhaus Siloah - Pforzheim
  • Pforzheim, Germany, 75179
    • Praxis fuer Innere Medizin am Krankenhaus Siloah - Pforzheim
  • Pinneberg, Germany, 25421
    • Gemeinschaftspraxis - Pinneberg
  • Potsdam, Germany, D-14467
    • Klinikum Ernst von Bergmann
  • Radebeul, Germany, D-01445
    • Kreiskrankenhaus Radebeul
  • Ravensburg, Germany, D-88212
    • Krankenhaus St. Elisabeth - Ravensburg
  • Ravensburg, Germany, 88212
    • Gemeinschaftspraxis - Ravensburg
  • Recklinghausen, Germany, 45661
    • Elisabeth Krankenhaus
  • Recklinghausen, Germany, DOH-45659
    • Prosper-Hospital Recklinghausen
  • Regensburg, Germany, 93047
    • Hematologische Onkologische Praxis
  • Regensburg, Germany, D-93049
    • Krankenhaus Barmherzige Brueder Regensburg
  • Regensburg, Germany, D-93042
    • Klinikum der Universitaet Regensburg
  • Rehling, Germany, 86508
    • Internistische Praxis Dres. Hempel und Hochdorfer
  • Remscheid, Germany, D-42859
    • Klinikum Remscheid GmbH
  • Rheine, Germany, 48431
    • Jakobi Krankenhaus
  • Rostock, Germany, D-18059
    • Klinikum Suedstadt Rostock
  • Rostock, Germany, 18057
    • Haematologische/Onkologische Schwerpunktpraxis - Rostock
  • Rostock, Germany, D-18055
    • Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
  • Rotenburg, Germany, DOH-27356
    • Diakonie - Krankenhaus
  • Russelsheim, Germany, 65428
    • Internistische Schwerpunktpraxis
  • Saarbrucken, Germany, D-66113
    • Caritasklinik St. Theresia
  • Saarbruecken, Germany, 66113
    • Gemeinschaftspraxis - Saarbruecken
  • Saarlouis, Germany, D-66713
    • St. Elizabeth-Klinik Saarlouis
  • Schleswig, Germany, D-24837
    • Martin - Luther Hospital
  • Schmiedeberg, Germany, 01762
    • Praxis fur Innere Medizin - Schmiedeberg
  • Schwabisch Hall, Germany, D-74523
    • Deaconess Hospital
  • Schweinfurt, Germany, 97421
    • Gemeinschaftspraxis fuer Haematologie und Internist - Schweinfurt
  • Schweinfurt, Germany, D-97422
    • Leopoldina - Krankenhaus
  • Schwelm, Germany, 58332
    • HELIOS Klinikum - Schwelm
  • Schwerin, Germany, D-19049
    • Klinikum Schwerin
  • Siegen, Germany, D-57072
    • St. Marien - Krankenhaus Siegen GMBH
  • Siegen, Germany, D-57074
    • Evang. Jung-Stilling Hospital
  • Solingen, Germany, D-42697
    • St. Lukas - Clinic Solingen
  • Stadtlohn, Germany, 48703
    • Krankenhaus Maria-Hilf - Stadtlohn
  • Straubing, Germany, 94315
    • Onkologische Schwerpunktpraxis - Straubing
  • Stuttgart, Germany, D-70174
    • Klinik fuer Onkologie - Katharinenhospital Stuttgart
  • Stuttgart, Germany, D-70176
    • Diakonie Klinikum Stuttgart
  • Stuttgart, Germany, D-70173
    • Haematologische Praxis
  • Stuttgart, Germany, 70374
    • Hospital Bad Cannstatt
  • Stuttgart, Germany, D-70176
    • Gastroenterologische und Haematologisch-Onkologische Praxis E. M. Dr. Hoering von Ehr Respondek
  • Stuttgart, Germany, D-70191
    • Klinikum Stuttgart - Buergerhospital
  • Stuttgart, Germany, D-70376
    • Robert-Bosch-Krankenhaus
  • Thuine, Germany, D-49832
    • St. Elisabeth Hospital Thuine
  • Traunstein, Germany, D-83278
    • Regional Hospital Traunstein
  • Trier, Germany, D-54219
    • Krankenanstalt Mutterhaus der Borromaerinnen
  • Trier, Germany, D-54292
    • Krankenhaus Der Barmherzigen Brueder
  • Trier, Germany, 54290
    • Onkologische Gemeinschaftspraxis - Trier
  • Troisdorf, Germany, 53840
    • Praxis Fuer Internistische Haematologie / Onkologie
  • Tuebingen, Germany, D-72076
    • Universitaetsklinikum Tuebingen
  • Tutzing, Germany, D-82327
    • Hospital Tutzing
  • Twistringen, Germany, D-27239
    • Praxis fuer Haematologie und Onkologie
  • Ulm, Germany, D-89081
    • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
  • Unna, Germany, D-59403
    • Ev. Hospital Unna
  • Vechta, Germany, D-49377
    • St. Marienhospital - Vechta
  • Villingen, Germany, 78050
    • Onkologische Schwerpunktpraxis - Villingen
  • Villingen-Schwenningen, Germany, D-78050
    • Municipal Hospital Complex
  • Waldbrol, Germany, D-51545
    • Regional Hospital Waldbrol
  • Weiden, Germany, D-92637
    • Haematologische Praxis
  • Weilheim, Germany, 82362
    • Gemeinschaftspraxis feur Haemotologie und Onkologie - Weilheim
  • Weimar, Germany, 99425
    • Sophien - und Hufeland - Klinikum Weimar gGmbH
  • Wendlingen, Germany, 73240
    • Onkologische Schwerpunktpraxis
  • Wernigerode, Germany, 38855
    • Harz-Klinikum Wernigerode-Blankenburg GmbH
  • Westerland, Germany, 25980
    • Asklepios Nordseeklinik Westerland GmbH
  • Westerstede, Germany, 26655
    • Ammerland-Klinik GmbH
  • Wetzlar, Germany, D-35578
    • Hospital Wetzler
  • Wiesbaden, Germany, D-65199
    • Dr. Horst-Schmidt-Kliniken
  • Wiesbaden, Germany, D-65191
    • Deutsche Klinik fuer Diagnostik
  • Witten, Germany, D-58455
    • Ev. Hospital Witten-Herdecke
  • Wittenberg, Germany, 06886
    • Evangelisches Krankenhaus - Lutherstadt Wittenberg
  • Wolfsburg, Germany, D-38440
    • Klinikum der Stadt Wolfsburg
  • Worms, Germany, 67547
    • Burkhard and Reimann Gemeinschaftspraxis
  • Wuerzburg, Germany, D-97070
    • Medizinische Poliklinik, Universitaet Wuerzburg
  • Wuppertal, Germany, D-42283
    • Helios Kliniken Wuppertal University Hospital
  • Wuppertal 2, Germany, D-42283
    • Kliniken St. Antonius
  • Zwickau, Germany, 08009
    • Heinrich-Braun-Krankenhaus Zwickau
• Italy
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
• Netherlands
  • Rotterdam, Netherlands, 3015 GJ
    • Erasmus MC - Sophia Children's Hospital
• Poland
  • Wroclaw, Poland, 50-367
    • Akademia Medyczna im. Piastow Slaskich
• Sweden
  • Goeteborg, Sweden, S-141685
    • Goeteborg University
• Switzerland
  • Aarau, Switzerland, CH-5001
    • Kantonsspital Aarau
  • Basel, Switzerland, CH-4005
    • Universitaets-Kinderspital beider Basel
  • Locarno, Switzerland, 6600
    • Ospedale "la Carita", Locarno
  • Lucerne 16, Switzerland, CH-6000
    • Kinderspital Luzern
  • St. Gallen, Switzerland, CH-9006
    • Ostschweizer Kinderspital
  • Zurich, Switzerland, CH-8032
    • University Children's Hospital
• United Kingdom
  • England
    • Manchester, England, United Kingdom, M27 4HA
      • Royal Manchester Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histological diagnosis of aggressive B-cell lymphoma

  • Previously untreated disease
  • Stage I-IV disease
• CD20-positive disease
• Any International Prognostic Index (IPI) score
• No secondary lymphoma after prior chemotherapy or radiotherapy
• No primary CNS lymphoma
• No primary gastrointestinal (MALT) lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• AST and ALT ≤ 3 times normal unless related to lymphoma
• Bilirubin ≤ 2 mg/dL unless related to lymphoma
• Creatinine ≤ 2 times normal unless related to lymphoma
• Fertile patients must use effective contraception
• No known allergic reactions against foreign proteins
• No active infections requiring systemically administered antibiotics or antiviral medications
• No noncompensated heart failure
• No dilatative cardiomyopathy
• No coronary heart disease with ST-segment depression in ECG
• No myocardial infarction during the past 6 months
• No chronic lung disease with hypoxemia
• No severe noncompensated hypertension
• No severe noncompensated diabetes mellitus
• No clinical signs of cerebral dysfunction
• No severe psychiatric disease
• No known HIV infection
• No active chronic hepatitis B or C infection
• No other concurrent diseases that exclude the administration of therapy as outlined by the study protocol

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 12 weeks since prior clinical trial participation
• No prior participation in this study
• No prior therapy, including murine antibody, for this cancer
• No prior organ transplantation
• No concurrent response-adapted radiotherapy ("iceberg radiotherapy")
• No other concurrent anticancer chemotherapy or other study medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interventional: CHOP-14 + 8 x 2-weekly rituximab; Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.	Drug: cyclophosphamide; Other: pharmacological study; Radiation: radiation therapy; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: rituximab; Biological: pegfilgrastim
Active Comparator: Interventional: CHOP-14 + 8 x dose-dense rituximab; Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.	Drug: cyclophosphamide; Other: pharmacological study; Radiation: radiation therapy; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: rituximab; Biological: pegfilgrastim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (in first 20 patients of each cohort with a distinct variation of the rituximab schedule) assessed on days -4, -1, 10, 29, 57, 99, 155, 239, 267, 295, 407, and 491 of treatment	-4 to 491 days of treatment
Safety and treatment related deaths at 3 months after study completion	3 months after study completion
Toxicity assessed by NCI criteria, adverse events, serious adverse events, protocol adherence, and treatment-related deaths at 3 months after study completion	3 months after study completion

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to treatment failure assessed at 2 years within the study and periodically thereafter	at 2 years within the study and periodically thereafterlif
Complete response rate assessed at 2 years within the study and periodically thereafter	at 2 years within the study and periodically thereafter
Progression rate	life-long
Survival time	life-long
Progression-free survival	life-long

Collaborators and Investigators

• Sponsor: German High-Grade Non-Hodgkin's Lymphoma Study Group
• Investigators: Study Chair: Norbert Schmitz, MD, PhD, Asklepios Klinik St. Georg

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: February 9, 2006
• First Submitted That Met QC Criteria: February 9, 2006
• First Posted (Estimate): February 13, 2006

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult Burkitt lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult Burkitt lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage I grade 1 follicular lymphoma; stage I grade 2 follicular lymphoma; stage I adult diffuse small cleaved cell lymphoma; contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage I adult Burkitt lymphoma; contiguous stage II adult Burkitt lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; stage I adult immunoblastic large cell lymphoma; contiguous stage II grade 3 follicular lymphoma; stage I grade 3 follicular lymphoma; contiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; stage I adult diffuse large cell lymphoma; stage I adult diffuse mixed cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: CDR0000454505; DSHNHL-2004-1; EU-20536; DSHNHL-CHOP-R-ESC; EUDRACT-2005-00529-68