Rituximab and Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
Conditions
Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, B-Cell
Conditions: Keywords
contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, nodal marginal zone B-cell lymphoma, anaplastic large cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II mantle cell lymphoma, stage I adult Burkitt lymphoma, stage I mantle cell lymphoma, stage III adult Burkitt lymphoma, stage III mantle cell lymphoma, stage IV adult Burkitt lymphoma, stage IV mantle cell lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: filgrastim Type: Biological
Name: rituximab Type: Biological
Name: cyclophosphamide Type: Drug
Name: doxorubicin hydrochloride Type: Drug
Name: prednisone Type: Drug
Name: vincristine sulfate Type: Drug
Name: radiation therapy Type: Radiation
Overall Status
Recruiting
Summary
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 hydrochloride, 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. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving rituximab and combination chemotherapy together with radiation therapy may kill more cancer cells. It is not yet known which schedule of rituximab and combination chemotherapy is more effective when given with or without radiation therapy in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy with or without radiation therapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES:

Primary

- Compare the time to treatment failure in patients with previously untreated, low-risk, aggressive, B-cell non-Hodgkin's lymphoma treated with 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone with vs without radiotherapy.

Secondary

- Compare the time to progression in patients treated with these regimens.

- Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.

- Compare the complete response rate in patients treated with these regimens.

- Compare the tumor control in patients treated with these regimens.

- Compare the safety of these regimens in these patients.

- Compare the pharmacoeconomics of these regimens.

- Compare patient adherence to these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to study center, serum lactic dehydrogenase level (≤ upper limit of normal [ULN] vs > ULN), disease stage (I or II vs III or IV), ECOG performance status (0-1 vs 2-3), bulky disease, and extranodal involvement. Patients with initial bulky disease and/or qualifying extranodal involvement are randomized to 1 of 4 treatment arms. Patients with non-bulky disease are randomized to treatment arms I or III.

All patients will be given the option of receiving a 1-week course of pretreatment therapy comprising vincristine IV once on day -6 and oral prednisone once daily on days -6 to 0.

- Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

- Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.

- Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

- Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.

Patients in all arms undergo restaging of their disease after courses 3 and 6 of R-CHOP. Patients with stable disease after 6 courses or disease progression after courses 3 or 6 proceed to salvage chemotherapy off study. Patients achieving a partial remission or an unconfirmed CR after 6 courses undergo additional restaging 4 weeks later. Patients with disease progression proceed to salvage chemotherapy off study. Patients who achieve CR after 6 courses of R-CHOP or have a confirmed CR after the additional restaging undergo radiotherapy according to randomization (as above).

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,072 patients will be accrued for this study.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 60 Years
Minimum Age: 18 Years
Gender: Both
Criteria: DISEASE CHARACTERISTICS:

- Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma, including the following subtypes:

- Grade 3 follicular lymphoma

- Diffuse B-cell lymphoma, including diffuse large cell lymphoma with the following variants:

- Centroblastic

- Immunoblastic

- Plasmablastic

- Anaplastic large cell

- T-cell-rich B-cell lymphoma

- Primary effusion lymphoma

- Intravascular B-cell lymphoma

- Primary mediastinal B-cell lymphoma

- Burkitt's or Burkitt-like lymphoma

- Mantle cell lymphoma (blastoid)

- Aggressive marginal zone lymphoma (monocytoid)

- Previously untreated disease

- CD20-positive disease

- International prognostic index (IPI) score 0 or 1 (age-adjusted)

- Only patients with bulky disease, as defined by largest single or conglomerate tumor ≥ 7.5 cm in diameter, are allowed to have an IPI score of 0

- No mucosa-associated lymphoid tissue (MALT) lymphoma

- No CNS involvement of lymphoma (intracerebral, meningeal, or intraspinal)

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Platelet count ≥ 100,000/mm³

- WBC ≥ 2,500/mm³

- No known hypersensitivity to the study medications

- No known HIV-positivity

- No active hepatitis infection

- Not pregnant or lactating

- Negative pregnancy test

- No other malignancy within the past 5 years except carcinoma in situ or basal cell skin cancer

- No impaired left ventricular function

- No severe cardiac arrhythmias

- No other impaired organ function

- No other serious disorder

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiotherapy

- No prior immunosuppressive treatment with cytostatics

- No concurrent participation in other treatment studies
Locations
Klinikum St. Marien
Amberg, Germany
Status: Recruiting
Contact: Ludwig Fischer von Weikersthal, MD - 49-96-2138-1637 - weikersthal.ludwig@gesundheitszentrum-klinikum.amberg.de
Klinikum Augsburg
Augsburg, Germany
Status: Recruiting
Contact: Gunter Schlimok, MD - 49-821-400-2353 - schlimok@klinikum-augsburg.de
Kreiskrankenhaus Aurich
Aurich, Germany
Status: Recruiting
Contact: Langer, MD - 49-4941-94-5000 - langer@kkh-aurich.de
Klinikum Bayreuth
Bayreuth, Germany
Status: Recruiting
Contact: Contact Person - 49-921-400-00
Charite - Campus Charite Mitte
Berlin, Germany
Status: Recruiting
Contact: Kurt Possinger, MD - 49-304-5051-3135 - kurt.possinger@charite.de
Charite University Hospital - Campus Virchow Klinikum
Berlin, Germany
Status: Recruiting
Contact: B Doerken, MD - 49-30-450-553-111
Franziskus Hospital
Bielefeld, Germany
Status: Recruiting
Contact: H.J. Weh, MD - 49-521-5897-1200
Augusta-Kranken-Anstalt gGmbH
Bochum, Germany
Status: Recruiting
Contact: Contact Person - 49-234-517-2430
Staedtisches Klinikum Braunschweig
Braunschweig, Germany
Status: Recruiting
Contact: Bernhard Woermann, MD - 49-531-595-3224 - b.woermann@klinikum-braunschweig.de
Klinikum Bremen-Mitte
Bremen, Germany
Status: Recruiting
Contact: Bernd Hertenstein, MD - 49-421-491-5240
Onkologische Schwerpunktpraxis Celle
Celle, Germany
Status: Recruiting
Contact: Felix Marquard, MD - 49-51- 41-95-16-16
Hospital Kuchwald Chemnitz
Chemnitz, Germany
Status: Recruiting
Contact: Contact Person - 49-371-333-0
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, Germany
Status: Recruiting
Contact: Marcel Reiser, MD - 49-221-478-4408 - marcel.reiser@uni-koeln.de
Praxis Fuer Haematologie Internistische Onkologie
Cologne, Germany
Status: Recruiting
Contact: C. Gabor, MD - 49-221-931-8220
Carl - Thiem - Klinkum Cottbus
Cottbus, Germany
Status: Recruiting
Contact: H. B. Steinhauer, MD - 49-355-46-2223
Klinikum Dortmund
Dortmund, Germany
Status: Recruiting
Contact: Michael Heike, MD - 49-231-9532-1770 - michael.heike@klinikumdo.de
Virngrund-Klinik Ellwangen
Ellwangen, Germany
Status: Recruiting
Contact: Johannes Zundler, MD - 49-7961-881-2301
Hans - Susemihl - Krankenhaus
Emden, Germany
Status: Recruiting
Contact: H. Becker, MD - 49-4921-98-1295 - h.becker@hsk-emden.de
St. Antonius Hospital
Eschweiler, Germany
Status: Recruiting
Contact: Contact Person - 49-240-376-1280
Universitaetsklinikum Essen
Essen, Germany
Status: Recruiting
Contact: Ulrich Duehrsen, MD - 49-201-723-2734 - ulrich.duehrsen@uk-essen.de
Klinikum Frankfurt (Oder) GmbH
Frankfurt (Oder), Germany
Status: Recruiting
Contact: Michael G. Kiehl, MD, PhD - 49-335-548-4601 - m.kiehl.km@klinikumffo.de
Klinikum der J.W. Goethe Universitaet
Frankfurt, Germany
Status: Recruiting
Contact: Lothar Bergmann, MD - 49-941-944-5501 - l.bergmann@em.uni-frankfurt.de
Krankenhaus Nordwest
Frankfurt, Germany
Status: Recruiting
Contact: Elke Jaeger, MD - 49-69-7601-3380
Universitaetsklinikum Freiburg
Freiburg, Germany
Status: Recruiting
Contact: Roland H. Mertelsmann, MD, PhD - 49-761-270-3541 - mertelsmann@mmll.ukl.uni-freiburg.de
Klinikum Garmisch - Partenkirchen GmbH
Garmisch-Partenkirchen, Germany
Status: Recruiting
Contact: L. Schulz, MD - 49-8821-77-1520 - lothar.schulz@klinikum-gap.de
Saint Josef Hospital
Gelsenkirchen, Germany
Status: Recruiting
Contact: G. Meckenstock, MD - 49-209-504-0 - gmeckenstock@kkel.de
Wilhelm-Anton-Hospital gGmbH, Goch
Goch, Germany
Status: Recruiting
Contact: Volker Runde, MD, PhD - 49-2823-891-115
Universitaetsklinikum Goettingen
Goettingen, Germany
Status: Recruiting
Contact: Lorenz H. Truemper, MD, PhD - 49-551-398-583 - lorenz.truemper@med.uni-goettingen.de
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
Greifswald, Germany
Status: Recruiting
Contact: Gottfried Doelken, MD - 49-3834-866-698 - doelken@uni-greifswald.de
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
Hagen, Germany
Status: Recruiting
Contact: Hartmut Eimermacher, MD - 49-2331-1290
Krankenhaus Martha-Maria Halle-Doelau gGmbH
Halle, Germany
Status: Recruiting
Contact: Contact Person - 49-345-559-1440
Asklepios Klinik St. Georg
Hamburg, Germany
Status: Recruiting
Contact: Norbert Schmitz, MD, PhD - 49-40-1818-85-2005 - Norbert.Schmitz@ak-stgeorg.lbk.hh.de
University Medical Center Hamburg - Eppendorf
Hamburg, Germany
Status: Recruiting
Contact: Liliana Daukaeva, MD - 49-40-7410-52-921
Klinikum Stadt Hanau
Hanau, Germany
Status: Recruiting
Contact: M. Burk, MD - 49-6181-296-4348
Krankenhaus Siloah - Medizinische Klinik II
Hannover, Germany
Status: Recruiting
Contact: Contact Person - 49-7231-498-3701
Medizinische Hochschule Hannover
Hannover, Germany
Status: Recruiting
Contact: Arnold Ganser, PhD, MD - 49-511-927-2802 - ganser.arnold@mh-hannover.de
Medizinische Universitaetsklinik und Poliklinik
Heidelberg, Germany
Status: Recruiting
Contact: Anthony D. Ho, MD, PhD - 49-6221-56-8001 - anthony_ho@med.uni-heidelberg.de
Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
Herrsching, Germany
Status: Recruiting
Contact: Hermann Dietzfelbinger, MD - 49-8152-29-260 - h.dietzfelbinger@klinik-schindlbeck.de
St. Bernward Krankenhaus
Hildesheim, Germany
Status: Recruiting
Contact: Ulrich Kaiser, MD - 49-5-121-90-12-73 - u.kaiser@bernward-khs.de
Haematologie und Internistische Onkologie Praxis
Homberg, Germany
Status: Recruiting
Contact: Wolfgang Weber, MD - 49-568-160-9950
Universitaetsklinikum des Saarlandes
Homburg, Germany
Status: Recruiting
Contact: Michael G.M. Pfreundschuh, MD - 49-6841-162-3084 - michael.pfreundschuh@uniklinik-saarland.de
Clinic for Bone Marrow Transplantation and Hematology and Oncology
Idar-Oberstein, Germany
Status: Recruiting
Contact: Axel A. Fauser, MD, PhD - 49-6781-66-1590 - office@bmt-center-io.com
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, Germany
Status: Recruiting
Contact: Martin Bentz - 49-721-974-3001
Internistische Gemeinschaftspraxis - Kassel
Kassel, Germany
Status: Recruiting
Contact: U. Soeling - 49-561-739-3372 - dr@soeling.de
Klinikum Kempten Oberallgaeu
Kempten, Germany
Status: Recruiting
Contact: Otto Pruemmer, MD - 49-831-530-2226 - otto.pruemmer@klinikum-kempten.de
Staedtisches Krankenhaus Kiel
Kiel, Germany
Status: Recruiting
Contact: Michael Kneba - 49-431-1697-120 - m.kneba@med2.uni-kiel.de
University Hospital Schleswig-Holstein - Kiel Campus
Kiel, Germany
Status: Recruiting
Contact: Michael Kneba - 49-431-1697-1201
Internistische Praxis - Landshut
Landshut, Germany
Status: Recruiting
Contact: Ursula Vehling-Kaiser - 49-871-275-381
Klinikum der Stadt Ludwigshafen am Rhein
Ludwigshafen am Rhein, Germany
Status: Recruiting
Contact: Michael J. Uppenkamp, MD - 49-621-503-3901 - UppenKamM@klilu.de
Kreiskrankenhaus Luedenscheid
Luedenscheid, Germany
Status: Recruiting
Contact: Gerhard Heil, MD - 49-235-1460
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, Germany
Status: Recruiting
Contact: Astrid Franke, MD - 49-391-671-3266
III Medizinische Klinik Mannheim
Mannheim, Germany
Status: Recruiting
Contact: Ruediger Hehlmann, MD - 49-621-383-4115 - Ruediger.Hehlmann@med3.ma.uni-heidelberg.de
Klinikum Minden
Minden, Germany
Status: Recruiting
Contact: Heinrich Bodenstein, MD - 49-571-801-4810 - heinrich.bodenstein@klinikum.minden.de
Krankenhaus Maria Hilf GmbH
Moenchengladbach, Germany
Status: Recruiting
Contact: Ullrich Graeven, MD, PhD - 49-2161-892-2201 - innere@mariahilf.de
Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
Muenster, Germany
Status: Recruiting
Contact: Christian Lerchenmueller, MD - 49-251-620-080
Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
Muenster, Germany
Status: Recruiting
Contact: Wolfgang E. Berdel, MD - 49-251-834-7587 - berdel@uni-muenster.de
Klinikum der Universitaet Muenchen - Grosshadern Campus
Munich, Germany
Status: Recruiting
Contact: Wolfgang Hiddemann, MD, PhD - 49-89-7095-2551
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany
Status: Recruiting
Contact: Ulrich Keller, MD - 49-89-4140-7435 - ulrich.keller@lrz.tum.de
Onkologische Schwerwpunktpraxis Dr. Ladda
Neumarkt, Germany
Status: Recruiting
Contact: Ekkehart Ladda, MD - 49-91-8146-4526 - ekkehart.ladda@gmx.de
Klinikum Oldenburg
Oldenburg, Germany
Status: Recruiting
Contact: Bernd Metzner, MD - 49-441-403-2614 - metzner.bernd@klinikum-oldenburg.de
Bruederkrankenhaus St. Josef Paderborn
Paderborn, Germany
Status: Recruiting
Contact: Thomas Wolff, MD - 49-5251-702-1425 - t.wolff@bk-paderborn.de
Klinikum der Universitaet Regensburg
Regensburg, Germany
Status: Recruiting
Contact: Reinhard Andreesen, MD - 49-941-944-5501 - reinhard.andreesen@klinik.uni-regensburg.de
Klinikum Suedstadt Rostock
Rostock, Germany
Status: Recruiting
Contact: B. Krammer-Steiner, MD - 49-381-4401-6100
Leopoldina - Krankenhaus
Schwienfurt, Germany
Status: Recruiting
Contact: Hans Reinel, MD - 49-9721-720-627 - hreinel@leopoldina.de
St. Marien - Krankenhaus Siegen GMBH
Siegen, Germany
Status: Recruiting
Contact: Contact Person - 49-271-231-0
Onkologische Schwerpunktpraxis - Straubing
Straubing, Germany
Status: Recruiting
Contact: Matthias Demandt, MD - 49-9421-90777
Diakonie Klinikum Stuttgart
Stuttgart, Germany
Status: Recruiting
Contact: Else G. Heidemann, MD - 49-711-991-3500
Klinik fuer Onkologie - Katharinenhospital Stuttgart
Stuttgart, Germany
Status: Recruiting
Contact: Hans-Guenther Mergenthaler, MD - 49-711-278-5601 - h.mergenthaler@katharinehospital.de
Krankenanstalt Mutterhaus der Borromaerinnen
Trier, Germany
Status: Recruiting
Contact: Michael Clemens, MD - 49-651-947-2571 - clemens@uni-trier.de
Krankenhaus Der Barmherzigen Brueder
Trier, Germany
Status: Recruiting
Contact: Koelbel, MD - 49-651-208-0
Praxis Fuer Internistische Haematologie / Onkologie
Troisdorf, Germany
Status: Recruiting
Contact: Helmut Forstbauer, MD - 49-2241-975-422
Praxis fuer Haematologie und Onkologie
Twistringen, Germany
Status: Recruiting
Contact: Georg Weissenborn, MD - 49-4243-602-714
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, Germany
Status: Recruiting
Contact: Hartmut Doehner, MD - 49-731-5002-4400 - hartmut.doehner@uniklinik-ulm.de
St. Marienhospital - Vechta
Vechta, Germany
Status: Recruiting
Contact: J. Diers, MD - 49-4441-99-0
Regional Hospital Waldbrol
Waldbrol, Germany
Status: Recruiting
Contact: Contact Person - 49-11-82-1313
Dr. Horst-Schmidt-Kliniken
Wiesbaden, Germany
Status: Recruiting
Contact: Norbert Frickhofen, MD - 49-611-433-018 - norbert.frickhofen@hsk-wiesbaden.de
Kliniken St. Antonius
Wuppertal 2, Germany
Status: Recruiting
Contact: Contact Person - 49-202-299-2591
Heinrich-Braun-Krankenhaus Zwickau
Zwickau, Germany
Status: Recruiting
Contact: Ute Kreibich, MD - 49-375-51-2331
Rabin Medical Center - Beilinson Campus
Petah-Tikva, Israel
Status: Recruiting
Contact: Contact Person - 972-3-937-7377
Start Date
November 2005
Sponsors
German High-Grade Non-Hodgkin's Lymphoma Study Group
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page