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

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 to 60 Other DSHNHL-2004-3 EUDRACT-2005-005218-19, EU-205111, NCT00278408

Objectives

Primary

1. 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

1. Compare the time to progression in patients treated with these regimens.
2. Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.
3. Compare the complete response rate in patients treated with these regimens.
4. Compare the tumor control in patients treated with these regimens.
5. Compare the safety of these regimens in these patients.
6. Compare the pharmacoeconomics of these regimens.
7. 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

A total of 1,072 patients will be accrued for this study.

Outcomes

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

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		Ph: 49-6841-162-3084 Email: michael.pfreundschuh@uniklinik-saarland.de

Germany
	Amberg
	Klinikum St. Marien
		Ludwig Fischer von Weikersthal, MD	Ph:  49-96-2138-1637
			Email: weikersthal.ludwig@gesundheitszentrum-klinikum.amberg.de
	Augsburg
	Klinikum Augsburg
		Gunter Schlimok, MD	Ph:  49-821-400-2353
			Email: schlimok@klinikum-augsburg.de
	Aurich
	Kreiskrankenhaus Aurich
		Langer, MD	Ph:  49-4941-94-5000
			Email: langer@kkh-aurich.de
	Bayreuth
	Klinikum Bayreuth
		Contact Person	Ph:  49-921-400-00
	Berlin
	Charite - Campus Charite Mitte
		Kurt Possinger, MD	Ph:  49-304-5051-3135
			Email: kurt.possinger@charite.de
	Charite University Hospital - Campus Virchow Klinikum
		B Doerken, MD	Ph:  49-30-450-553-111
	Bielefeld
	Franziskus Hospital
		H.J. Weh, MD	Ph:  49-521-5897-1200
	Bochum
	Augusta-Kranken-Anstalt gGmbH
		Contact Person	Ph:  49-234-517-2430
	Braunschweig
	Staedtisches Klinikum Braunschweig
		Bernhard Woermann, MD	Ph:  49-531-595-3224
			Email: b.woermann@klinikum-braunschweig.de
	Bremen
	Klinikum Bremen-Mitte
		Bernd Hertenstein, MD	Ph:  49-421-491-5240
	Celle
	Onkologische Schwerpunktpraxis Celle
		Felix Marquard, MD	Ph:  49-51- 41-95-16-16
	Chemnitz
	Hospital Kuchwald Chemnitz
		Contact Person	Ph:  49-371-333-0
	Cologne
	Medizinische Universitaetsklinik I at the University of Cologne
		Marcel Reiser, MD	Ph:  49-221-478-4408
			Email: marcel.reiser@uni-koeln.de
	Praxis Fuer Haematologie Internistische Onkologie
		C. Gabor, MD	Ph:  49-221-931-8220
	Cottbus
	Carl - Thiem - Klinkum Cottbus
		H. B. Steinhauer, MD	Ph:  49-355-46-2223
	Dortmund
	Klinikum Dortmund
		Michael Heike, MD	Ph:  49-231-9532-1770
			Email: michael.heike@klinikumdo.de
	Ellwangen
	Virngrund-Klinik Ellwangen
		Johannes Zundler, MD	Ph:  49-7961-881-2301
	Emden
	Hans - Susemihl - Krankenhaus
		H. Becker, MD	Ph:  49-4921-98-1295
			Email: h.becker@hsk-emden.de
	Eschweiler
	St. Antonius Hospital
		Contact Person	Ph:  49-240-376-1280
	Essen
	Universitaetsklinikum Essen
		Ulrich Duehrsen, MD	Ph:  49-201-723-2734
			Email: ulrich.duehrsen@uk-essen.de
	Frankfurt
	Klinikum der J.W. Goethe Universitaet
		Lothar Bergmann, MD	Ph:  49-941-944-5501
			Email: l.bergmann@em.uni-frankfurt.de
	Krankenhaus Nordwest
		Elke Jaeger, MD	Ph:  49-69-7601-3380
	Frankfurt (Oder)
	Klinikum Frankfurt (Oder) GmbH
		Michael Kiehl, MD, PhD	Ph:  49-335-548-4601
			Email: m.kiehl.km@klinikumffo.de
	Freiburg
	Universitaetsklinikum Freiburg
		Roland Mertelsmann, MD, PhD	Ph:  49-761-270-3541
			Email: mertelsmann@mmll.ukl.uni-freiburg.de
	Garmisch-Partenkirchen
	Klinikum Garmisch - Partenkirchen GmbH
		L. Schulz, MD	Ph:  49-8821-77-1520
			Email: lothar.schulz@klinikum-gap.de
	Gelsenkirchen
	Saint Josef Hospital
		G. Meckenstock, MD	Ph:  49-209-504-0
			Email: gmeckenstock@kkel.de
	Goch
	Wilhelm-Anton-Hospital gGmbH, Goch
		Volker Runde, MD, PhD	Ph:  49-2823-891-115
	Goettingen
	Universitaetsklinikum Goettingen
		Lorenz Truemper, MD, PhD	Ph:  49-551-398-583
			Email: lorenz.truemper@med.uni-goettingen.de
	Greifswald
	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
		Gottfried Doelken, MD	Ph:  49-3834-866-698
			Email: doelken@uni-greifswald.de
	Hagen
	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
		Hartmut Eimermacher, MD	Ph:  49-2331-1290
	Halle
	Krankenhaus Martha-Maria Halle-Doelau gGmbH
		Contact Person	Ph:  49-345-559-1440
	Hamburg
	Asklepios Klinik St. Georg
		Norbert Schmitz, MD, PhD	Ph:  49-40-1818-85-2005
			Email: Norbert.Schmitz@ak-stgeorg.lbk.hh.de
	University Medical Center Hamburg - Eppendorf
		Liliana Daukaeva, MD	Ph:  49-40-7410-52-921
	Hanau
	Klinikum Stadt Hanau
		M. Burk, MD	Ph:  49-6181-296-4348
	Hannover
	Krankenhaus Siloah - Medizinische Klinik II
		Contact Person	Ph:  49-7231-498-3701
	Medizinische Hochschule Hannover
		Arnold Ganser, PhD, MD	Ph:  49-511-927-2802
			Email: ganser.arnold@mh-hannover.de
	Heidelberg
	Medizinische Universitaetsklinik und Poliklinik
		Anthony Ho, MD, PhD	Ph:  49-6221-56-8001
			Email: anthony_ho@med.uni-heidelberg.de
	Herrsching
	Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
		Hermann Dietzfelbinger, MD	Ph:  49-8152-29-260
			Email: h.dietzfelbinger@klinik-schindlbeck.de
	Hildesheim
	St. Bernward Krankenhaus
		Ulrich Kaiser, MD	Ph:  49-5-121-90-12-73
			Email: u.kaiser@bernward-khs.de
	Homberg
	Haematologie und Internistische Onkologie Praxis
		Wolfgang Weber, MD	Ph:  49-568-160-9950
	Homburg
	Universitaetsklinikum des Saarlandes
		Michael Pfreundschuh, MD	Ph:  49-6841-162-3084
			Email: michael.pfreundschuh@uniklinik-saarland.de
	Idar-Oberstein
	Clinic for Bone Marrow Transplantation and Hematology and Oncology
		Axel Fauser, MD, PhD	Ph:  49-6781-66-1590
			Email: office@bmt-center-io.com
	Karlsruhe
	Staedtisches Klinikum Karlsruhe gGmbH
		Martin Bentz	Ph:  49-721-974-3001
	Kassel
	Internistische Gemeinschaftspraxis - Kassel
		U. Soeling	Ph:  49-561-739-3372
			Email: dr@soeling.de
	Kempten
	Klinikum Kempten Oberallgaeu
		Otto Pruemmer, MD	Ph:  49-831-530-2226
			Email: otto.pruemmer@klinikum-kempten.de
	Kiel
	Staedtisches Krankenhaus Kiel
		Michael Kneba	Ph:  49-431-1697-120
			Email: m.kneba@med2.uni-kiel.de
	University Hospital Schleswig-Holstein - Kiel Campus
		Michael Kneba	Ph:  49-431-1697-1201
	Landshut
	Internistische Praxis - Landshut
		Ursula Vehling-Kaiser	Ph:  49-871-275-381
	Ludwigshafen am Rhein
	Klinikum der Stadt Ludwigshafen am Rhein
		Michael Uppenkamp, MD	Ph:  49-621-503-3901
			Email: UppenKamM@klilu.de
	Luedenscheid
	Kreiskrankenhaus Luedenscheid
		Gerhard Heil, MD	Ph:  49-235-1460
	Magdeburg
	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
		Astrid Franke, MD	Ph:  49-391-671-3266
	Mannheim
	III Medizinische Klinik Mannheim
		Ruediger Hehlmann, MD	Ph:  49-621-383-4115
			Email: Ruediger.Hehlmann@med3.ma.uni-heidelberg.de
	Minden
	Klinikum Minden
		Heinrich Bodenstein, MD	Ph:  49-571-801-4810
			Email: heinrich.bodenstein@klinikum.minden.de
	Moenchengladbach
	Krankenhaus Maria Hilf GmbH
		Ullrich Graeven, MD, PhD	Ph:  49-2161-892-2201
			Email: innere@mariahilf.de
	Muenster
	Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
		Christian Lerchenmueller, MD	Ph:  49-251-620-080
	Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
		Wolfgang Berdel, MD	Ph:  49-251-834-7587
			Email: berdel@uni-muenster.de
	Munich
	Klinikum der Universitaet Muenchen - Grosshadern Campus
		Wolfgang Hiddemann, MD, PhD	Ph:  49-89-7095-2551
	Klinikum Rechts Der Isar - Technische Universitaet Muenchen
		Ulrich Keller, MD	Ph:  49-89-4140-7435
			Email: ulrich.keller@lrz.tum.de
	Neumarkt
	Onkologische Schwerwpunktpraxis Dr. Ladda
		Ekkehart Ladda, MD	Ph:  49-91-8146-4526
			Email: ekkehart.ladda@gmx.de
	Oldenburg
	Klinikum Oldenburg
		Bernd Metzner, MD	Ph:  49-441-403-2614
			Email: metzner.bernd@klinikum-oldenburg.de
	Paderborn
	Bruederkrankenhaus St. Josef Paderborn
		Thomas Wolff, MD	Ph:  49-5251-702-1425
			Email: t.wolff@bk-paderborn.de
	Regensburg
	Klinikum der Universitaet Regensburg
		Reinhard Andreesen, MD	Ph:  49-941-944-5501
			Email: reinhard.andreesen@klinik.uni-regensburg.de
	Rostock
	Klinikum Suedstadt Rostock
		B. Krammer-Steiner, MD	Ph:  49-381-4401-6100
	Schwienfurt
	Leopoldina - Krankenhaus
		Hans Reinel, MD	Ph:  49-9721-720-627
			Email: hreinel@leopoldina.de
	Siegen
	St. Marien - Krankenhaus Siegen GMBH
		Contact Person	Ph:  49-271-231-0
	Straubing
	Onkologische Schwerpunktpraxis - Straubing
		Matthias Demandt, MD	Ph:  49-9421-90777
	Stuttgart
	Diakonie Klinikum Stuttgart
		Else Heidemann, MD	Ph:  49-711-991-3500
	Klinik fuer Onkologie - Katharinenhospital Stuttgart
		Hans-Guenther Mergenthaler, MD	Ph:  49-711-278-5601
			Email: h.mergenthaler@katharinehospital.de
	Trier
	Krankenanstalt Mutterhaus der Borromaerinnen
		Michael Clemens, MD	Ph:  49-651-947-2571
			Email: clemens@uni-trier.de
	Krankenhaus Der Barmherzigen Brueder
		Koelbel, MD	Ph:  49-651-208-0
	Troisdorf
	Praxis Fuer Internistische Haematologie / Onkologie
		Helmut Forstbauer, MD	Ph:  49-2241-975-422
	Twistringen
	Praxis fuer Haematologie und Onkologie
		Georg Weissenborn, MD	Ph:  49-4243-602-714
	Ulm
	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
		Hartmut Dohner, MD	Ph:  49-731-5002-4400
			Email: hartmut.doehner@uniklinik-ulm.de
	Vechta
	St. Marienhospital - Vechta
		J. Diers, MD	Ph:  49-4441-99-0
	Waldbrol
	Regional Hospital Waldbrol
		Contact Person	Ph:  49-11-82-1313
	Wiesbaden
	Dr. Horst-Schmidt-Kliniken
		Norbert Frickhofen, MD	Ph:  49-611-433-018
			Email: norbert.frickhofen@hsk-wiesbaden.de
	Wuppertal 2
	Kliniken St. Antonius
		Contact Person	Ph:  49-202-299-2591
	Zwickau
	Heinrich-Braun-Krankenhaus Zwickau
		Ute Kreibich, MD	Ph:  49-375-51-2331
Israel
	Petah-Tikva
	Rabin Medical Center - Beilinson Campus
		Contact Person	Ph:  972-3-937-7377

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

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