Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma

Randomised Study Comparing 6 And 8 Cycles Of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine And Prednisone) At 14-Day Intervals (CHOP-14), Both With Or Without The Monoclonal Anti-CD20 Antibody Rituximab In Patients Aged 61 To 80 Years With Aggressive Non-Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide, doxorubicin, vincristine, and prednisone together with or without rituximab works in treating older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer randomized as of 6/2005).

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Biological: rituximab; Drug: CHOP regimen; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma.
• Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens.
• Compare the rate of complete remission, rate of primary progression, tumor control, disease-free survival, overall survival, and relapse after radiotherapy in patients treated with these regimens.
• Compare the safety and side effects of these regimens in these patients.

Secondary

• Compare short-term and long-term side effects of these regimens in these patients.
• Compare quality of life of patients treated with these regimens.
• Compare the cost of these regimens in these patients.
• Determine relapse in patients treated with these regimens who received involved-field radiotherapy.

OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label, multicenter study. Patients are stratified according to participating center, value for serum lactic dehydrogenase (no greater than upper limit of normal [ULN] vs greater than ULN), bulky disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0 or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms. Patients with CD20-negative lymphoma are randomized to arms I or II only.

• Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to day 0 before initiating CHOP chemotherapy.
• Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses.
• Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm I for a total of 8 courses.
• Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.
• Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery of bone marrow, and after complete remision of mucositis, patients with sites of initial bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.

• Study Type: Interventional
• Enrollment (Actual): 1506
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52070
    • Haematologisch Onkologische Praxis
  • Amberg, Germany, D-92224
    • Klinikum St. Marien
  • Ansbach, Germany, 91522
    • Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
  • Aschaffenburg, Germany, 63739
    • Specialist Practice for Oncology
  • Aschaffenburg, Germany, 63739
    • II. Medizinische Klinik
  • Augsburg, Germany, D-86156
    • Klinikum Augsburg
  • Augsburg, Germany, 86150
    • Haematologische Praxis
  • Augsburg, Germany, 86150
    • Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
  • Aurich, Germany, D-26603
    • Kreiskrankenhaus Aurich
  • Bad Hersfeld, Germany, 36251
    • Regional Hospital Bad Hersfeld
  • Bad Saarow, Germany, 15523
    • Humaine - Clinic
  • Bayreuth, Germany, D-95445
    • Krankenhaus Hohe Warte Mediziniche Klinik
  • Berlin, Germany, 13357
    • Haematologisch-Onkologische Schwerpunktpraxis
  • Berlin, Germany, 13125
    • Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
  • Bernburg, Germany, 06406
    • Hospital Complex Bernburg
  • Bietigheim, Germany, D-74321
    • Krankenhaus Bietigheim
  • Bocholt, Germany, 46397
    • Saint Agnes Hospital
  • Bochum, Germany, 44791
    • Saint Josef Hospital
  • Bochum, Germany, D-44892
    • Knappschaft Krankenhaus
  • Bonn, Germany, D-53111
    • Medizinische Poliklinik
  • Bonn, Germany, D-53113
    • Rheinische Friedrich-Wilhelms-Universitat
  • Bremen, Germany, 28239
    • DIAKO Ev. Diakonie Krankenhaus gGmbH
  • Bunde, Germany, D-32257
    • Medizinische Klinik Am Lukas - Krankenhaus
  • Celle, Germany, 29223
    • General Hospital
  • Chemnitz, Germany, 09113
    • Hospital Kuchwald Chemnitz
  • Cologne, Germany, D-50677
    • Praxis Fuer Haematologie Internistische Onkologie
  • Cologne, Germany, D-50924
    • Medizinische Universitaetsklinik I at the University of Cologne
  • Cologne-Kalk, Germany, D-51105
  • Cologne-Merheim, Germany, D-51109
    • Lung Clinic Cologne-Merheim
  • Cottbus, Germany, 03048
    • Carl - Thiem - Klinkum Cottbus
  • Darmstadt, Germany, D-64283
    • Klinikum Darmstadt
  • Dortmund, Germany, 44137
    • Saint Johannes Hospital Dortmund
  • Dresden, Germany, D-01307
    • Universitätsklinikum Carl Gustav Carus
  • Duisburg, Germany, 47166
    • St. Johannes Hospital - Medical Klinik II
  • Dulmen, Germany, 48249
    • Franz Hospital Dulmen
  • Dusseldorf, Germany, 40489
    • Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth
  • Emden, Germany, 26721
    • Hans - Susemihl - Krankenhaus
  • Erfurt, Germany, D-99089
    • Klinikum Erfurt
  • Eschweiler, Germany, 52249
    • St. Antonius Hospital
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Frankfurt, Germany, D-60488
    • Krankenhaus Nordwest
  • Frankfurt/Oder, Germany, D-15236
    • Klinikum Frankfurt (Oder) GmbH
  • Freiburg, Germany, 79110
    • Evang. Deaconess Hospital Freiburg
  • Fulda, Germany, D-36043
    • Municipal Hospital Complex
  • Gehrden, Germany, 30989
    • Robert - Koch Hospital
  • Gießen, Germany, 35392
    • Centre for Internal Medicine Gieben
  • Greifswald, Germany, 17489
    • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
  • Gutersloh, Germany, 33332
    • Staedtisches Klinikum Guetersloh
  • Göttingen, Germany, 37075
    • Universitaetsklinikum Goettingen
  • Hagen, Germany, 58095
    • Allgemeines Krankenhaus Hagen
  • Hagen, Germany, 58095
    • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
  • Halle, Germany, 06120
    • Krankenhaus Martha-Maria Halle-Doelau gGmbH
  • Halle, Germany, D-06120
    • Universitaetsklinikum Halle
  • Halle/Saale, Germany, 06110
    • Krankenhaus St. Elisabeth und St. Barbara
  • Hamburg, Germany, 20095
  • Hamburg, Germany, D-22767
    • Haematologisch-Onkologische Praxis Altona
  • Hamburg, Germany, 22763
    • Allgemeines Krankenhaus Altona
  • Hamburg, Germany, 20251
    • University Medical Center Hamburg - Eppendorf
  • Hamburg, Germany, 22413
    • Asklepios Klinik Nord Heidberg
  • Hamm, Germany, 59063
    • Evangelische Krankenhaus Hamm
  • Hannover, Germany, D-30625
    • Medizinische Hochschule Hannover
  • Hannover, Germany, 30159
  • Hannover, Germany, D-30449
    • Krankenhaus Siloah - Medizinische Klinik II
  • Hannover, Germany, 30559
    • Henriettenstiftung Krankenhaus
  • Harrislee, Germany, D-24955
    • Oncology Specialists Clinic
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg
  • Heidelberg, Germany, D-69115
    • Medizinische Universitaetsklinik und Poliklinik
  • 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
    • Onkologische Schwerpunktpraxis
  • Holzminden, Germany, 37603
    • Evang. Hospital
  • Homburg, Germany, D-66421
    • Medical University Hospital Homburg
  • Hoyerswerda, Germany, 02977
    • Hospital Complex Hoyerswerda
  • Jena, Germany, D-07743
    • Gemeinschaftspraxis Innere Medizin
  • Jena, Germany, D-07747
    • Klinikum der Friedrich-Schiller Universitaet Jena
  • Kaiserslautern, Germany, D-67655
    • Municipal Hospital Complex of the University
  • Karlsruhe, Germany, 76133
    • Staedtisches Klinikum Karlsruhe gGmbH
  • Kassel, Germany, 34121
    • Red Cross Hospital Kassel
  • Kiel, Germany, 23116
    • Staedtisches Krankenhaus Kiel
  • Koblenz, Germany, D-56068
    • Praxis fuer Haematologie und Onkologie
  • Koblenz, Germany, 56068
    • Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH
  • Kornwestheim, Germany, D-70806
    • Leonardis Clinic
  • Krefeld, Germany, D-47805
    • Klinikum Krefeld GmbH
  • Kronach, Germany, 96317
    • Frankenwald Klinik
  • Lebach, Germany, 66822
    • Caritas - Krakenhaus Lebach
  • Leipzig, Germany, 04103
    • University Leipzig Clinic of Internal Medicine
  • Leipzig, Germany, 04129
    • Klinikum "St. Georg" Leipzig
  • Leipzig, Germany, D-04103
  • Lemgo, Germany, D-32657
    • Klinikum Lippe - Lemgo
  • Limburg, Germany, 65549
    • St. Vincenz Hospital Limburg
  • Lingen, Germany, 49808
    • St. Bonifatius Hospital Lingen
  • Lippstadt, Germany, 59555
    • Dreifaltigkeits Hospital
  • Ludwigsburg, Germany, D-71640
    • Klinikum Ludwigsburg
  • Ludwigshafen, Germany, 67067
    • St. Marien Hospital Ludwighafen
  • Ludwigshafen, Germany, D-67063
    • Municipal Complex of Ludwigshafen
  • Luebeck, Germany, D-23538
    • Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
  • Magdeburg, Germany, 39104
    • Staedtisches Klinikum Magdeburg - Altstadt
  • Magdeburg, Germany, 39120
    • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
  • Mainz, Germany, 55131
    • Johannes Gutenberg University
  • Mannheim, Germany, D-68305
    • III Medizinische Klinik Mannheim
  • Marburg, Germany, D-35043
    • Universitaetsklinikum Giessen und Marburg GmbH - Marburg
  • Marburg, Germany, D-35037
  • Mayen, Germany, 56727
    • Regional Hospital Mayen
  • Minden, Germany, D-32423
    • Klinikum Minden
  • Minden, Germany, D-32427
  • Monchengladbach, Germany, 41061
    • Ev. Hospital Bethesda
  • Monchengladbach, Germany, 41063
    • Hospital Maria-Hilf II
  • Monchenglasbach/Rheydt, Germany, D-41239
  • Mulheim/Ruhr, Germany, 45466
    • Evangelisches Krankenhaus - Mülheim
  • Mulheim/Ruhr, Germany, 45468
    • St. Marien Hospital - Muelheim an der Ruhr
  • Munchberg, Germany, 95213
    • Kreiskrankenhaus Muenchberg
  • Munich, Germany, D-81377
    • Klinikum der Universitaet Muenchen - Grosshadern Campus
  • Munich, Germany, D-80335
    • Munich Oncologic Practice at Elisenhof
  • Munich, Germany, D-81737
    • Municipal Hospital Munich
  • Munich, Germany, D-80336
    • Klinikum der Universitaet Muenchen - Innenstadt Campus
  • Munich, Germany, D-80804
    • Krankenhaus Muenchen Schwabing
  • Munster, Germany, D-48129
    • Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
  • Neumarkt, Germany, 92318
    • Regional Hospital Neumarkt
  • Neunkirchen, Germany, 66538
    • Staedtisches Klinikum Neunkirchen gGmbH
  • Neuss, Germany, D-41464
    • Lukaskrankenhaus Neuss
  • Nuremberg, Germany, D-90340
    • Klinikum Nuernberg - Klinikum Nord
  • Offenburg, Germany, D-77654
    • Klinikum Offenburg
  • Oldenburg, Germany, D-26133
    • Klinikum Oldenburg
  • Oldenburg, Germany, 26121
    • Hematologische Praxis
  • Oldenburg, Germany, 26122
    • Ev. Hospital Oldenburg
  • Osnabrück, Germany, D-49076
    • Paracelsus - Klinik Osnabrueck
  • Pforzheim, Germany, D-75175
    • Municipal Hospital Complex
  • Potsdam, Germany, D-14467
    • Klinikum Ernst von Bergmann
  • Radebeul, Germany, D-01445
    • Kreiskrankenhaus Radebeul
  • Ravensburg, Germany, 88212
    • Krankenhaus St. Elisabeth - Ravensburg
  • Regensburg, Germany, 93047
    • Hematologische Onkologische Praxis
  • Regensburg, Germany, D-93049
    • Krankenhaus Barmherzige Brueder Regensburg
  • Regensburg, Germany, 93042
    • Klinikum der Universitaet Regensburg
  • Rheine, Germany, 48431
    • Jakobi Krankenhaus
  • Rostock, Germany, D-18257
  • Rostock, Germany, 18057
    • Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
  • Rostock, Germany, 18059
    • Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock
  • Saarbrucken, Germany, 66113
    • Caritasklinik St. Theresia
  • Saarbruecken, Germany, D-66113
    • Schwerpunktpraxis fuer Haematologie und Onkologie
  • Saarlouis, Germany, 66713
    • St. Elizabeth-Klinik Saarlouis
  • Schleswig, Germany, D-24837
    • Martin - Luther Hospital
  • Schwabisch Hall, Germany, 74523
    • Deaconess Hospital
  • Schweinfurt, Germany, D-97422
    • Leopoldina - Krankenhaus
  • Siegen, Germany, 57074
    • Evang. Jung-Stilling Hospital
  • Solingen, Germany, 42697
    • St. Lukas - Clinic Solingen
  • Stuttgart, Germany, 70376
    • Robert-Bosch-Krankenhaus
  • Stuttgart, Germany, 70374
    • Hospital Bad Cannstatt
  • Stuttgart, Germany, 70174
    • Klinik fuer Onkologie - Katharinenhospital Stuttgart
  • Stuttgart, Germany, 70176
    • Diakonie Klinikum Stuttgart
  • Stuttgart, Germany, 70191
    • Klinikum Stuttgart - Buergerhospital
  • Thuine, Germany, 49832
    • St. Elisabeth Hospital Thuine
  • Traunstein, Germany, 83278
    • Regional Hospital Traunstein
  • Trier, Germany, D-54290
    • Krankenanstalt Mutterhaus der Borromaerinnen
  • Trier, Germany, D-54290
  • Trier, Germany, D-54292
    • Krankenhaus Barmherzigen Brueder
  • Tutzing, Germany, 82327
    • Hospital Tutzing
  • Ulm, Germany, 89081
    • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
  • Unna, Germany, 59403
    • Ev. Hospital Unna
  • Vechta, Germany, 49377
    • St. Marienhospital - Vechta
  • Villingen-Schwenningen, Germany, D-78045
    • Municipal Hospital Complex
  • Waldbrol, Germany, 51545
    • Regional Hospital Waldbrol
  • Werden, Germany, 45239
    • Evangelisches Krankenhaus Essen Werden
  • Wetzlar, Germany, 35578
    • Hospital Wetzler
  • Wiesbaden, Germany, 65199
    • Dr. Horst-Schmidt-Kliniken
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik fuer Diagnostik
  • Witten, Germany, 58455
    • Ev. Hospital Witten-Herdecke
  • Wuppertal, Germany, 42283
    • Kliniken St. Antonius
  • Wurzburg, Germany, 97070
    • University Würzburg
  • Zwickau, Germany, D-08060
    • Municipal Hospital Complex Zwickau
• Switzerland
  • Zurich, Switzerland, 8063
    • City Hospital Triemli
  • Zurich, Switzerland, 8091
    • UniversitaetsSpital Zuerich

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:

• Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) by an excisional biopsy of a lymph node or an extensive biopsy of an extranodal involvement (if there is no lymph node involvement)
• CD20^+ B-cell lymphoma or CD20^- B-cell and T-cell lymphoma allowed

• B-cell NHL including the following:

  • Stage III follicular lymphoma
  • Stage III follicular lymphoma and diffuse B-cell lymphoma
  • Lymphoblastic precursor B-cell lymphoma

  • Diffuse large cell B-cell lymphoma

    • Centroblastic
    • Immunoblastic
    • Plasmablastic
    • Anaplastic large cell
    • T-cell-rich B-cell lymphoma
    • Primary effusion lymphoma
    • Intravasal B-cell lymphoma
    • Primary mediastinal B-cell lymphoma
  • Mantle zone lymphoma, blastoid
  • Burkitt's lymphoma
  • Burkitt-like lymphoma
  • Aggressive marginal zone lymphoma (monocytoid)

• T-cell NHL including the following:

  • Lymphoblastic precursor T-cell lymphoma

  • Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS)

    • Lennert's lymphoma
    • T-zone lymphoma
  • T-cell lymphoma of the angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) type

  • Anaplastic large cell lymphoma

    • ALK^+
    • ALK^-
  • Extranodal NK/T-cell lymphoma, nasal type

  • Intestinal T/NK-cell lymphoma (with or without enteropathy)

    • Hepatosplenic gamma-delta lymphoma
    • Subcutaneous panniculitis-like PTCL
    • Aggressive T/NK PTCL
  • Anaplastic large-cell NHL, NOS
• Bone marrow involvement no more than 25%
• No lymphoma that is clearly restricted to the CNS or originating from the gastrointestinal tract

PATIENT CHARACTERISTICS:

Age

• 61 to 80

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• No active hepatitis infection

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• No Canadian Cardiovascular Society class III or IV angina pectoris
• No New York Heart Association class III or IV cardiac failure
• Ejection fraction at least 50%
• Fractional shortenings at least 25% by echocardiography or nuclear medicine examination

Pulmonary

• FEV1 at least 50%
• Diffusion capacity at least 50%

Other

• No uncontrolled diabetes mellitus
• No known hypersensitivity to any study medications
• No other concurrent malignancy
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• Must not have already initiated lymphoma therapy (except for the prephase treatment specified for this study)
• No other concurrent lymphoma therapy
• No concurrent participation in another treatment study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S6; 6x CHOP-14	Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Drug: CHOP regimen; Radiation: radiation therapy; 36Gy on BULK and extranodal involvement
Experimental: R6; 6x CHOP-14 + 8x Rituximab	Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Biological: rituximab; Drug: CHOP regimen; Radiation: radiation therapy; 36Gy on BULK and extranodal involvement
Experimental: S8; 8x CHOP-14	Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Drug: CHOP regimen; Radiation: radiation therapy; 36Gy on BULK and extranodal involvement
Experimental: R8; 8x CHOP-14 + 8x Rituximab	Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Biological: rituximab; Drug: CHOP regimen; Radiation: radiation therapy; 36Gy on BULK and extranodal involvement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to treatment failure at 3 years within the study and then periodically after study completion	3 years within the study and then periodically after study completion

Secondary Outcome Measures

Outcome Measure	Time Frame
Complete response rate at 3 years within the study and then periodically after study completion	3 years within the study and then periodically after
Progression rate	3 years within the study and then periodically after
Survival	3 years within the study and then periodically after
Tumor control	3 years within the study and then periodically after
Disease-free survival	3 years within the study and then periodically after

Collaborators and Investigators

• Sponsor: German High-Grade Non-Hodgkin's Lymphoma Study Group

Publications and helpful links

General Publications

• Muller C, Murawski N, Wiesen MH, Held G, Poeschel V, Zeynalova S, Wenger M, Nickenig C, Peter N, Lengfelder E, Metzner B, Rixecker T, Zwick C, Pfreundschuh M, Reiser M. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012 Apr 5;119(14):3276-84. doi: 10.1182/blood-2011-09-380949. Epub 2012 Feb 15.
• Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15.
• Kuhnl A, Cunningham D, Counsell N, Hawkes EA, Qian W, Smith P, Chadwick N, Lawrie A, Mouncey P, Jack A, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Rosenwald A, Ott G, Horn H, Ziepert M, Pfreundschuh M, Linch D. Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial. Ann Oncol. 2017 Jul 1;28(7):1540-1546. doi: 10.1093/annonc/mdx128.
• Pfreundschuh M, Poeschel V, Zeynalova S, Hanel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. doi: 10.1200/JCO.2013.54.6861. Epub 2014 Nov 17. Erratum In: J Clin Oncol. 2015 Jun 10;33(17):1991.
• Bittenbring JT, Neumann F, Altmann B, Achenbach M, Reichrath J, Ziepert M, Geisel J, Regitz E, Held G, Pfreundschuh M. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol. 2014 Oct 10;32(29):3242-8. doi: 10.1200/JCO.2013.53.4537. Epub 2014 Aug 18.
• Held G, Murawski N, Ziepert M, Fleckenstein J, Poschel V, Zwick C, Bittenbring J, Hanel M, Wilhelm S, Schubert J, Schmitz N, Loffler M, Rube C, Pfreundschuh M. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1112-8. doi: 10.1200/JCO.2013.51.4505. Epub 2014 Feb 3.
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Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): August 5, 2010
• Study Completion (Actual): August 5, 2010

Study Registration Dates

• First Submitted: January 24, 2003
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

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

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Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage III adult Burkitt lymphoma; stage IV adult diffuse 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 mantle cell lymphoma; stage IV mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; stage I marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; contiguous stage II marginal zone lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; stage III adult T-cell leukemia/lymphoma; stage IV adult T-cell leukemia/lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage I mantle cell lymphoma; stage I adult Burkitt lymphoma; contiguous stage II adult Burkitt lymphoma; contiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma; stage I adult T-cell leukemia/lymphoma; stage II adult T-cell leukemia/lymphoma; contiguous stage II adult lymphoblastic lymphoma; stage I adult lymphoblastic lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; 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: CDR0000269015; DSHNHL-1999-1A (Other Grant/Funding Number: Deutsche Krebshilfe); EU-20243 (Other Identifier: Ethikkommission der Ärztekammer des Saarlandes [85/99])