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Phase III Randomized Study of Immunochemotherapy Comprising Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) With Versus Without Radiotherapy in Patients With Previously Untreated, Low-Risk, Aggressive, B-Cell Non-Hodgkin's Lymphoma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Rituximab and Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
Basic Trial Information
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Protocol IDs
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Phase III
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Treatment
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Active
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18 to 60
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Other
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DSHNHL-2004-3 EUDRACT-2005-005218-19, EU-205111, NCT00278408
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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.
Entry 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)
Prior/Concurrent Therapy:
- No prior chemotherapy or radiotherapy
- No prior immunosuppressive treatment with cytostatics
- No concurrent participation in other treatment studies
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
Expected Enrollment 1072A total of 1,072 patients will be accrued for this study. Outcomes Primary Outcome(s)Time to treatment failure (TTF) measured from day 1 of course 1 of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy up to 3 years on study with life-long follow-up
Secondary Outcome(s)Complete response (CR) rate until first relapse Progression rate during treatment Survival Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored) Disease-free survival measured from day 1 of course 1 of CHOP therapy Relapse-free survival of patients with complete response (CR) or unconfirmed complete response (CRu) following complete immunochemotherapy Safety (adverse events, serious adverse events) assessed at 3 months after completion of study treatment Consolidating radiotherapy
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.
Trial Contact Information
Trial Lead Organizations German High-Grade Non-Hodgkin's Lymphoma Study Group | | | Michael Pfreundschuh, MD, Protocol chair | | | | Trial Sites
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Germany |
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Amberg |
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| | | Klinikum St. Marien |
| | Ludwig Fischer von Weikersthal, MD | |
| Email:
weikersthal.ludwig@gesundheitszentrum-klinikum.amberg.de |
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Augsburg |
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| | Klinikum Augsburg |
| | Gunter Schlimok, MD | |
| Email:
schlimok@klinikum-augsburg.de |
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Aurich |
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| | Kreiskrankenhaus Aurich |
| | Langer, MD | |
| Email:
langer@kkh-aurich.de |
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Bayreuth |
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| | Klinikum Bayreuth |
| | Contact Person | |
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Berlin |
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| | Charite - Campus Charite Mitte |
| | Kurt Possinger, MD | |
| Email:
kurt.possinger@charite.de |
| | Charite University Hospital - Campus Virchow Klinikum |
| | B Doerken, MD | |
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Bielefeld |
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| | Franziskus Hospital |
| | H.J. Weh, MD | |
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Bochum |
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| | Augusta-Kranken-Anstalt gGmbH |
| | Contact Person | |
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Braunschweig |
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| | Staedtisches Klinikum Braunschweig |
| | Bernhard Woermann, MD | |
| Email:
b.woermann@klinikum-braunschweig.de |
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Bremen |
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| | Klinikum Bremen-Mitte |
| | Bernd Hertenstein, MD | |
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Celle |
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| | Onkologische Schwerpunktpraxis Celle |
| | Felix Marquard, MD | |
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Chemnitz |
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| | Hospital Kuchwald Chemnitz |
| | Contact Person | |
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Cologne |
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| | Medizinische Universitaetsklinik I at the University of Cologne |
| | Marcel Reiser, MD | |
| Email:
marcel.reiser@uni-koeln.de |
| | Praxis Fuer Haematologie Internistische Onkologie |
| | C. Gabor, MD | |
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Cottbus |
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| | Carl - Thiem - Klinkum Cottbus |
| | H. B. Steinhauer, MD | |
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Dortmund |
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| | Klinikum Dortmund |
| | Michael Heike, MD | |
| Email:
michael.heike@klinikumdo.de |
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Ellwangen |
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| | Virngrund-Klinik Ellwangen |
| | Johannes Zundler, MD | |
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Emden |
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| | Hans - Susemihl - Krankenhaus |
| | H. Becker, MD | |
| Email:
h.becker@hsk-emden.de |
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Eschweiler |
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| | St. Antonius Hospital |
| | Contact Person | |
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Essen |
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| | Universitaetsklinikum Essen |
| | Ulrich Duehrsen, MD | |
| Email:
ulrich.duehrsen@uk-essen.de |
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Frankfurt |
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| | Klinikum der J.W. Goethe Universitaet |
| | Lothar Bergmann, MD | |
| Email:
l.bergmann@em.uni-frankfurt.de |
| | Krankenhaus Nordwest |
| | Elke Jaeger, MD | |
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Frankfurt (Oder) |
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| | Klinikum Frankfurt (Oder) GmbH |
| | Michael Kiehl, MD, PhD | |
| Email:
m.kiehl.km@klinikumffo.de |
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Freiburg |
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| | Universitaetsklinikum Freiburg |
| | Roland Mertelsmann, MD, PhD | |
| Email:
mertelsmann@mmll.ukl.uni-freiburg.de |
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Garmisch-Partenkirchen |
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| | Klinikum Garmisch - Partenkirchen GmbH |
| | L. Schulz, MD | |
| Email:
lothar.schulz@klinikum-gap.de |
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Gelsenkirchen |
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| | Saint Josef Hospital |
| | G. Meckenstock, MD | |
| Email:
gmeckenstock@kkel.de |
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Goch |
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| | Wilhelm-Anton-Hospital gGmbH, Goch |
| | Volker Runde, MD, PhD | |
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Goettingen |
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| | Universitaetsklinikum Goettingen |
| | Lorenz Truemper, MD, PhD | |
| Email:
lorenz.truemper@med.uni-goettingen.de |
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Greifswald |
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| | Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet |
| | Gottfried Doelken, MD | |
| Email:
doelken@uni-greifswald.de |
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Hagen |
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| | St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH |
| | Hartmut Eimermacher, MD | |
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Halle |
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| | Krankenhaus Martha-Maria Halle-Doelau gGmbH |
| | Contact Person | |
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Hamburg |
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| | Asklepios Klinik St. Georg |
| | Norbert Schmitz, MD, PhD | |
| Email:
Norbert.Schmitz@ak-stgeorg.lbk.hh.de |
| | University Medical Center Hamburg - Eppendorf |
| | Liliana Daukaeva, MD | |
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Hanau |
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| | Klinikum Stadt Hanau |
| | M. Burk, MD | |
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Hannover |
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| | Krankenhaus Siloah - Medizinische Klinik II |
| | Contact Person | |
| | Medizinische Hochschule Hannover |
| | Arnold Ganser, PhD, MD | |
| Email:
ganser.arnold@mh-hannover.de |
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Heidelberg |
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| | Medizinische Universitaetsklinik und Poliklinik |
| | Anthony Ho, MD, PhD | |
| Email:
anthony_ho@med.uni-heidelberg.de |
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Herrsching |
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| | Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
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| | Hermann Dietzfelbinger, MD | |
| Email:
h.dietzfelbinger@klinik-schindlbeck.de |
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Hildesheim |
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| | St. Bernward Krankenhaus |
| | Ulrich Kaiser, MD | |
| Email:
u.kaiser@bernward-khs.de |
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Homberg |
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| | Haematologie und Internistische Onkologie Praxis |
| | Wolfgang Weber, MD | |
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Homburg |
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| | Universitaetsklinikum des Saarlandes |
| | Michael Pfreundschuh, MD | |
| Email:
michael.pfreundschuh@uniklinik-saarland.de |
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Idar-Oberstein |
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| | Clinic for Bone Marrow Transplantation and Hematology and Oncology |
| | Axel Fauser, MD, PhD | |
| Email:
office@bmt-center-io.com |
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Karlsruhe |
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| | Staedtisches Klinikum Karlsruhe gGmbH |
| | Martin Bentz | |
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Kassel |
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| | Internistische Gemeinschaftspraxis - Kassel |
| | U. Soeling | |
| Email:
dr@soeling.de |
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Kempten |
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| | Klinikum Kempten Oberallgaeu |
| | Otto Pruemmer, MD | |
| Email:
otto.pruemmer@klinikum-kempten.de |
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Kiel |
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| | Staedtisches Krankenhaus Kiel |
| | Michael Kneba | |
| Email:
m.kneba@med2.uni-kiel.de |
| | University Hospital Schleswig-Holstein - Kiel Campus |
| | Michael Kneba | |
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Landshut |
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| | Internistische Praxis - Landshut |
| | Ursula Vehling-Kaiser | |
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Ludwigshafen am Rhein |
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| | Klinikum der Stadt Ludwigshafen am Rhein |
| | Michael Uppenkamp, MD | |
| Email:
UppenKamM@klilu.de |
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Luedenscheid |
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| | Kreiskrankenhaus Luedenscheid |
| | Gerhard Heil, MD | |
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Magdeburg |
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| | Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg |
| | Astrid Franke, MD | |
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Mannheim |
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| | III Medizinische Klinik Mannheim |
| | Ruediger Hehlmann, MD | |
| Email:
Ruediger.Hehlmann@med3.ma.uni-heidelberg.de |
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Minden |
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| | Klinikum Minden |
| | Heinrich Bodenstein, MD | |
| Email:
heinrich.bodenstein@klinikum.minden.de |
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Moenchengladbach |
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| | Krankenhaus Maria Hilf GmbH |
| | Ullrich Graeven, MD, PhD | |
| Email:
innere@mariahilf.de |
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Muenster |
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| | Haematologisch - Onkologische Gemeinschaftspraxis - Muenster |
| | Christian Lerchenmueller, MD | |
| | Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster |
| | Wolfgang Berdel, MD | |
| Email:
berdel@uni-muenster.de |
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Munich |
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| | Klinikum der Universitaet Muenchen - Grosshadern Campus |
| | Wolfgang Hiddemann, MD, PhD | |
| | Klinikum Rechts Der Isar - Technische Universitaet Muenchen |
| | Ulrich Keller, MD | |
| Email:
ulrich.keller@lrz.tum.de |
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Neumarkt |
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| | Onkologische Schwerwpunktpraxis Dr. Ladda |
| | Ekkehart Ladda, MD | |
| Email:
ekkehart.ladda@gmx.de |
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Oldenburg |
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| | Klinikum Oldenburg |
| | Bernd Metzner, MD | |
| Email:
metzner.bernd@klinikum-oldenburg.de |
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Paderborn |
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| | Bruederkrankenhaus St. Josef Paderborn |
| | Thomas Wolff, MD | |
| Email:
t.wolff@bk-paderborn.de |
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Regensburg |
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| | Klinikum der Universitaet Regensburg |
| | Reinhard Andreesen, MD | |
| Email:
reinhard.andreesen@klinik.uni-regensburg.de |
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Rostock |
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| | Klinikum Suedstadt Rostock |
| | B. Krammer-Steiner, MD | |
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Schwienfurt |
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| | Leopoldina - Krankenhaus |
| | Hans Reinel, MD | |
| Email:
hreinel@leopoldina.de |
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Siegen |
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| | St. Marien - Krankenhaus Siegen GMBH |
| | Contact Person | |
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Straubing |
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| | Onkologische Schwerpunktpraxis - Straubing |
| | Matthias Demandt, MD | |
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Stuttgart |
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| | Diakonie Klinikum Stuttgart |
| | Else Heidemann, MD | |
| | Klinik fuer Onkologie - Katharinenhospital Stuttgart |
| | Hans-Guenther Mergenthaler, MD | |
| Email:
h.mergenthaler@katharinehospital.de |
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Trier |
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| | Krankenanstalt Mutterhaus der Borromaerinnen |
| | Michael Clemens, MD | |
| Email:
clemens@uni-trier.de |
| | Krankenhaus Der Barmherzigen Brueder |
| | Koelbel, MD | |
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Troisdorf |
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| | Praxis Fuer Internistische Haematologie / Onkologie |
| | Helmut Forstbauer, MD | |
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Twistringen |
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| | Praxis fuer Haematologie und Onkologie |
| | Georg Weissenborn, MD | |
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Ulm |
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| | Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm |
| | Hartmut Dohner, MD | |
| Email:
hartmut.doehner@uniklinik-ulm.de |
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Vechta |
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| | St. Marienhospital - Vechta |
| | J. Diers, MD | |
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Waldbrol |
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| | Regional Hospital Waldbrol |
| | Contact Person | |
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Wiesbaden |
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| | Dr. Horst-Schmidt-Kliniken |
| | Norbert Frickhofen, MD | |
| Email:
norbert.frickhofen@hsk-wiesbaden.de |
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Wuppertal 2 |
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| | Kliniken St. Antonius |
| | Contact Person | |
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Zwickau |
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| | Heinrich-Braun-Krankenhaus Zwickau |
| | Ute Kreibich, MD | |
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Israel |
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Petah-Tikva |
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| | | Rabin Medical Center - Beilinson Campus |
| | Contact Person | |
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Registry Information | | Official Title | | Randomized Study Comparing an Immuno-Chemotherapy with 6 Cycles of the Monoclonal Anti-CD20 Antibody Rituximab in Combination with 6 Cycles of Chemotherapy with CHOP ( Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) at 21-day Intervals or 14-day Intervals, Both With or Without Consolidating Radiotherapy or Large Tumour Masses (≥7.5 cm) and/or Extranodal Involvement in Patients with Aggressive CD20+ B-Cell Lymphoma Aged 18 to 60 Years with Age-Adjusted IPI=1 (all) or IPI=0 with a Large Tumour Mass (≥7.5 cm) [UNFOLDER 21/14 Study] | | Trial Start Date | | 2005-11-01 | | Trial Completion Date | | 2015-04-30 (estimated) | | Registered in ClinicalTrials.gov | | NCT00278408 | | Date Submitted to PDQ | | 2005-11-14 | | Information Last Verified | | 2008-12-07 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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