LymphomaPhase 3NCT00278408
Rituximab and Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
A Phase 3 study testing filgrastim, rituximab and cyclophosphamide in people with Lymphoma, run by German High-Grade Non-Hodgkin's Lymphoma Study Group at 152 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- filgrastim, rituximab and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 700 participants
- Where
- 152 sitesin 4 countries
- Study dates
- 2 Jan 2006to Feb 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
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
Trial locations and contacts
152 sites in 4 countries.
152 sites in 4 countries
Germany138 sites
GMP Tummes/Weinberg
Aachen
Klinikum St. Marien
Amberg, D-92224
Klinikum Augsburg
Augsburg, DOH-86156
Kreiskrankenhaus Aurich
Aurich, 26603
Klinikum Bayreuth
Bayreuth, D-95445
Charite - Campus Charite Mitte
Berlin, D-10117
Charite University Hospital - Campus Virchow Klinikum
Berlin, D-13353
Helios Klinikum Berlin-Buch, Department of Hematology and Stem Cell Transplantation
Berlin
Franziskus Hospital
Bielefeld, D-33615
Augusta-Kranken-Anstalt gGmbH
Bochum, D-44791
Johanniter Krankenhaus Bonn
Bonn
Universitätsklinikum Bonn
Bonn
Staedtisches Klinikum Braunschweig
Braunschweig, D-38114
Klinikum Bremen-Mitte
Bremen, D-28205
Evangelisches Diakonie-Krankenhaus gGmbH, Department of Internal Medicine
Bremen
Praxis Dr. Obst
Burgwedel
Onkologische Schwerpunktpraxis Celle
Celle, D-29221
Hospital Kuchwald Chemnitz - Department of Internal Medicine III
Chemnitz, 09113
Klinikum Chemnitz
Chemnitz
Klinikum Coburg
Coburg
Praxis Fuer Haematologie Internistische Onkologie
Cologne, D-50677
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, D-50924
Gemeinschaftspraxis Dres. Schmitz, Steinmetz, Severin
Cologne
Krankenhaus Holweide
Cologne
Lungenklinik Köln-Merheim
Cologne
Carl - Thiem - Klinkum Cottbus
Cottbus, D-03048
Klinikum Dortmund
Dortmund, D-44137
Virngrund-Klinik Ellwangen
Ellwangen, 73479
Hans - Susemihl - Krankenhaus
Emden, 26721
Universitätsklinikum Erlangen
Erlangen
St. Antonius Hospital
Eschweiler, DOH-52249
Universitaetsklinikum Essen
Essen, D-45122
Klinikum Esslingen
Esslingen am Neckar
Krankenhaus Nordwest
Frankfurt, D-60488
Klinikum der J.W. Goethe Universitaet
Frankfurt, D-60590
Klinikum Frankfurt (Oder) GmbH
Frankfurt (Oder), D-15236
Universitaetsklinikum Freiburg
Freiburg im Breisgau, D-79106
GMP Dres. Marschner, Zaiss, Kirste, Semsek
Freiburg im Breisgau
Praxis Dr. med. Reiber
Freiburg im Breisgau
Klinikum Fulda
Fulda
Klinikum Garmisch - Partenkirchen GmbH
Garmisch-Partenkirchen, D-82467
Saint Josef Hospital
Gelsenkirchen, D-45899
Praxis Dr. med. Schliesser
Giessen
Wilhelm-Anton-Hospital gGmbH, Goch
Goch, D-47574
Universitaetsklinikum Goettingen, Department of Hematology and Oncology
Göttingen, D-37075
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
Greifswald, D-17475
Gemeinschaftspraxis
Güstrow
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
Hagen, D-58095
Krankenhaus Martha-Maria Halle-Doelau gGmbH
Halle, D-06120
GMP Rohrberg, Hurtz, Schmidt, Frank-Gleich
Halle
Asklepios Klinik St. Georg
Hamburg, D-20099
University Medical Center Hamburg - Eppendorf
Hamburg, D-20246
Hämatologisch-onkologische Praxis Altona (HOPA)
Hamburg
Evangelisches Krankenhaus Hamm
Hamm
Klinikum Stadt Hanau
Hanau, 63450
Krankenhaus Siloah - Medizinische Klinik II
Hanover, D-30449
Medizinische Hochschule Hannover
Hanover, D-30625
Medizinische Universitaetsklinik und Poliklinik
Heidelberg, 69115
Klinikum Kreis Herford
Herford
Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
Herrsching am Ammersee, D-82211
St. Bernward Krankenhaus
Hildesheim, D-31134
Evangelisches Krankenhaus Holzminden
Holzminden
Haematologie und Internistische Onkologie Praxis
Homberg (Efze), D-34576
Universitaetsklinikum des Saarlandes
Homburg, D-66424
Clinic for Bone Marrow Transplantation and Hematology and Oncology
Idar-Oberstein, D-55743
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, 76133
St. Vincentius Kliniken Karlsruhe
Karlsruhe
Internistische Gemeinschaftspraxis - Kassel
Kassel, D-34117
Klinikum Kempten Oberallgaeu
Kempten, D-87439
Staedtisches Krankenhaus Kiel
Kiel, 23116
University Hospital Schleswig-Holstein - Kiel Campus
Kiel, D-24116
Gemeinschaftspraxis Dres. Heymanns, Weide, Thomalla
Koblenz
Praxis Dr. Stauch
Kronach
Internistische Praxis - Landshut
Landshut, 84028
Klinikum Landshut
Landshut
Caritas Krankenhaus Lebach
Lebach
Onkologische Schwerpunktpraxis Dr. Lothar Müller
Leer
Klinikum St. Georg Leipzig
Leipzig
Onkologische Praxis am Diakonissenhaus
Leipzig
Klinikum Lippe-Lemgo
Lemgo
Universitätsklinikum Schleswig-Holstein
Lübeck
Kreiskrankenhaus Luedenscheid
Lüdenscheid, 58515
St. Marienkrankenhaus
Ludwigshafen
Klinikum der Stadt Ludwigshafen am Rhein
Ludwigshafen am Rhein, D-67063
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, D-39120
Krankenhaus Altstadt Magdeburg
Magdeburg
III Medizinische Klinik Mannheim
Mannheim, D-68305
Mannheimer Onkologie Praxis
Mannheim
Universitätsklinikum Gießen und Marburg (UKGM)
Marburg
Klinikum Minden
Minden, D-32423
Krankenhaus Maria Hilf GmbH
Mönchengladbach, D-41063
Gemeinschaftspraxis Dres. Schröder, Sieg
Mülheim
Klinikum der Universitaet Muenchen - Grosshadern Campus
Munich, D-81377
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, D-81675
Gemeinschaftspraxis Abenhardt, Bojko, Bosse, Riedner
Munich
Städtisches Klinikum München Harlaching
Munich
Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
Münster, D-48149
Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
Münster, D-48149
Stauferklinikum Schwäbisch Gmünd
Mutlangen
Onkologische Schwerwpunktpraxis Dr. Ladda
Neumarkt, D-92318
Lukaskrankenhaus Neuss
Neuss
BRK Schloßbergklinik Oberstaufen
Oberstaufen
GMP Dres. Balló, Böck
Offenbach
Klinikum Oldenburg - Department of Hematology and Oncology
Oldenburg, D-26133
Pius Hospital Oldenburg, Department of Internal Oncology
Oldenburg
Paracelsus Krankenhaus Ruit
Ostfildern
Bruederkrankenhaus St. Josef Paderborn
Paderborn, D-33098
Krankenhaus Siloah
Pforzheim
Praxis Dr. Dencausse
Pforzheim
Klinikum der Universitaet Regensburg
Regensburg, D-93053
Krankenhaus Barmherzige Brüder Regensburg
Regensburg
Klinikum am Steinenberg
Reutlingen
Klinikum Suedstadt Rostock
Rostock, D-18059
Universitätsklinikum Rostock
Rostock
Gemeinschaftspraxis Dres. Jacobs, Daus, Schmits
Saarbrücken
Leopoldina - Krankenhaus
Schweinfurt, D-97422
St. Marien - Krankenhaus Siegen GMBH
Siegen, D-57072
Onkologische Schwerpunktpraxis - Straubing
Straubing, 94315
Klinik fuer Onkologie - Katharinenhospital Stuttgart
Stuttgart, D-70174
Diakonie Klinikum Stuttgart
Stuttgart, D-70176
Bürgerhospital
Stuttgart
Krankenanstalt Mutterhaus der Borromaerinnen
Trier, D-54219
Krankenhaus Der Barmherzigen Brueder
Trier, D-54292
Praxis Fuer Internistische Haematologie / Onkologie
Troisdorf, 53840
Universitätsklinikum Tübingen, Department of Internal Medicine II
Tübingen
Praxis fuer Haematologie und Onkologie
Twistringen, D-27239
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, D-89081
Katharinen Hospital Unna
Unna
St. Marienhospital - Vechta
Vechta, D-49377
Praxis VS-Villingen
Villingen-Schwenningen
Regional Hospital Waldbrol
Waldbröl, D-51545
Med. Versorgungszentrum Weiden
Weiden
Harz-Klinikum-Wernigerode
Wernigerode
Ammerland Klinik GmbH Westerstede
Westerstede
Dr. Horst-Schmidt-Kliniken
Wiesbaden, D-65199
Kliniken St. Antonius
Wuppertal, D-42283
Helios Klinikum Wuppertal
Wuppertal
Heinrich-Braun-Krankenhaus Zwickau
Zwickau, 08060
Italy11 sites
Ospidale A. Cardarelli
Campobasso
Azienda Ospedaliera di Cosenza
Cosenza
AOU San Martino Genova
Genova
Az. Ospedaliera Messina
Messina
Policlinico Universitario "G. Martino" Messina
Messina
Centro Oncologico Modenese, University of Modena and Reggio Emilia
Modena
Ematologia - OSP. Civile Piacenza
Piacenza
A. Santa Maria Nuova, Hematology Azienda
Reggio Emilia
Osp. S. Vincenzo - Taormina
Taormina
Ospedale San Giuseppe Moscati
Taranto
Ospedale di circolo e Fondazione Macchi Varese
Varese
Denmark2 sites
Rigshospitalet, Department of Hematology
Copenhagen
Amtssygehuset i Herlev
Herlev
About this study
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]
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.
Read the 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.
- Conditions
- Lymphoma
- Being tested
- filgrastim, rituximab, cyclophosphamide, doxorubicin hydrochloride, prednisone
- 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
- Medical subject headings
- Lymphoma, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large-Cell, Anaplastic, Lymphoma, Large-Cell, Immunoblastic, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
rituximabBiological
cyclophosphamideDrug
prednisoneDrug
radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Interventional: 6 R-CHOP-21 | Active comparator | 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. Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate |
| Interventional: 6 R-CHOP-21 + radiotherapy | Active comparator | 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. Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Radiation: radiation therapy |
| Interventional: 6 R-CHOP-14 | Active comparator | 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. Receives: Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate |
| Interventional: 6 R-CHOP-14 and radiotherapy | Active comparator | 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. Receives: Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
3 Years Event-free Survival
Event-free survival was the primary endpoint, which was defined as the time from randomization until one of the following events had occurred: progression during therapy, partial response, no change, unknown status at the end of study therapy, relapse after complete response or unconfirmed complete response, death from any cause; or additional treatment, whichever came first.
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Secondary outcomes (9)
3 Years Progression-free Survival
Progression of disease is defined as: recurrence of disease symptoms, development of new lymphatic or extralymphatic lesions or marked increase in lymphoma manifestation size by more than 25% in comparison with baseline.
Measured: Each patient will be observed for 3 years starting from completion of treatment.
3 Years Overall Survival
Overall survival was defined as the time from randomization to death of any cause.
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Rate of Complete Remissions and Progressive Disease
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Number of Patients With a Relapse After a CR/CRu
Relapse is defined as, recurrence of disease symptoms, development of new lymphatic or extralymphatic lesions or a marked increase in lymphoma manifestation size by more thyn 25% after at least 2 months CR or CRu from the time point of the final restaging examination
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Safety (Adverse Events, Serious Adverse Events, Rate of Secondary Neoplasia, Selected Laboratory Parameters, Including Leucocytes, Thrombocytes, and Haemoglobin)
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Absolute Dose Vincristine and Prednisone in mg (Median)
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Health-economic Aspects - Number of Patients Who Received Antibiotic Intervention and/or Red Blood Cell and Platelet Transfusion
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Total Duration of Chemotherapy in Days (Median)
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Absolute Dose Cyclophosphamide, Doxorubicin and Rituximab in mg/m² (Median)
Measured: Each patient will be observed for 3 years starting from completion of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2006 (estimated)
- Study start2 Jan 2006
- Primary completionFeb 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 700 participants (actual)
Sponsor and investigators
- Lead sponsor
- German High-Grade Non-Hodgkin's Lymphoma Study Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael G.M. Pfreundschuh, MD †, Study chair, Universitaetsklinikum des SaarlandesViola Poeschel, MD, Study director, Study Office Homburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00278408
- Sponsor's protocol ID
- CDR0000459796
- Other IDs
- DSHNHL-2004-3, EUDRACT-2005-005218-19, EU-205111
- Status last verified
- May 2025
- First submitted
- 16 Jan 2006
- Last updated
- 26 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Radiotherapy (RT) to bulky (B) and extralymphatic (E) disease in combination with 6xR-CHOP-14 or R-CHOP-21 in young good-prognosis DLBCL patients: Results of the 2x2 randomized UNFOLDER trial of the DSHNHL/GLA. Michael Pfreundschuh, Niels Murawski, Marita Ziepert, Bettina Altmann, Martin H. Dreyling, Peter Borchmann, Stefano Luminari, Mathias Witzens-Harig, Judith Dierlamm, Mathias Haenel, Lorenz Truemper, Bernd Metzner, Eva Lengfelder, Ulrich B. Keller, Christian Ruebe, Christian Berdel, Norbert Schmitz, Gerhard Held, and Viola Poeschel Journal of Clinical Oncology 2018 36:15_suppl, 7574-7574
Role of radiotherapy and dose-densification of R-CHOP in primary mediastinal B-cell lymphoma: A subgroup analysis of the unfolder trial of the German Lymphoma Alliance (GLA). Gerhard Held, Lorenz Thurner, Viola Poeschel, Christian Berdel, German Ott, Christian Schmidt, Andreas Viardot, Peter Borchmann, Ofer Shpilberg, Maike Nickelsen, Massimo Federico, Peter de Nully Brown, Niels Murawski, Lorenz H. Trumper, Heinz Schmidberger, Christian Ruebe, Jochen Fleckenstein, Norbert Schmitz, Markus Loeffler, Marita Ziepert, and German Lymphoma Alliance Journal of Clinical Oncology 2020 38:15_suppl, 8041-8041
Thurner L, Ziepert M, Berdel C, Schmidt C, Borchmann P, Kaddu-Mulindwa D, Viardot A, Witzens-Harig M, Dierlamm J, Haenel M, Metzner B, Wulf G, Lengfelder E, Keller UB, Frickhofen N, Nickelsen M, Gaska T, Griesinger F, Mahlberg R, Marks R, Shpilberg O, Lindemann HW, Soekler M, Fischer von Weikersthal L, Kiehl M, Roemer E, Bentz M, Krammer-Steiner B, Trappe R, de Nully Brown P, Federico M, Merli F, Engelhard M, Glass B, Schmitz N, Truemper L, Bewarder M, Hartmann F, Murawski N, Stilgenbauer S, Rosenwald A, Altmann B, Schmidberger H, Fleckenstein J, Loeffler M, Poeschel V, Held G. Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study. Hemasphere. 2023 Jul 5;7(7):e904. doi: 10.1097/HS9.0000000000000904. eCollection 2023 Jul.
PubMed 37427146
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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]
- ClinicalTrials.gov ID
- NCT00278408
- Acronym / sponsor ID
- CDR0000459796
- Conditions
- Lymphoma
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 700 participants (actual)
- Lead sponsor
- German High-Grade Non-Hodgkin's Lymphoma Study GroupUniversity, hospital or other
- Study start
- 2 Jan 2006
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 18 Jan 2006 (estimated)
- Results
- Posted 26 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Interventional: 6 R-CHOP-21 | Active comparator | Biological: rituximab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: prednisone, Drug: vincristine sulfateArm 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. |
| Interventional: 6 R-CHOP-21 + radiotherapy | Active comparator | Biological: rituximab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: prednisone, Drug: vincristine sulfate, Radiation: radiation therapyArm 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. |
| Interventional: 6 R-CHOP-14 | Active comparator | Biological: filgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: prednisone, Drug: vincristine sulfateArm 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. |
| Interventional: 6 R-CHOP-14 and radiotherapy | Active comparator | Biological: filgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: prednisone, Drug: vincristine sulfate, Radiation: radiation therapyArm 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastim | Biological | Interventional: 6 R-CHOP-14, Interventional: 6 R-CHOP-14 and radiotherapy |
| rituximab | Biological | Interventional: 6 R-CHOP-14, Interventional: 6 R-CHOP-14 and radiotherapy, Interventional: 6 R-CHOP-21, Interventional: 6 R-CHOP-21 + radiotherapy |
| cyclophosphamide | Drug | Interventional: 6 R-CHOP-14, Interventional: 6 R-CHOP-14 and radiotherapy, Interventional: 6 R-CHOP-21, Interventional: 6 R-CHOP-21 + radiotherapy |
| doxorubicin hydrochloride | Drug | Interventional: 6 R-CHOP-14, Interventional: 6 R-CHOP-14 and radiotherapy, Interventional: 6 R-CHOP-21, Interventional: 6 R-CHOP-21 + radiotherapy |
| prednisone | Drug | Interventional: 6 R-CHOP-14, Interventional: 6 R-CHOP-14 and radiotherapy, Interventional: 6 R-CHOP-21, Interventional: 6 R-CHOP-21 + radiotherapy |
| vincristine sulfate | Drug | Interventional: 6 R-CHOP-14, Interventional: 6 R-CHOP-14 and radiotherapy, Interventional: 6 R-CHOP-21, Interventional: 6 R-CHOP-21 + radiotherapy |
| radiation therapy | Radiation | Interventional: 6 R-CHOP-14 and radiotherapy, Interventional: 6 R-CHOP-21 + radiotherapy |
Primary outcome
3 Years Event-free Survival
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Event-free survival was the primary endpoint, which was defined as the time from randomization until one of the following events had occurred: progression during therapy, partial response, no change, unknown status at the end of study therapy, relapse after complete response or unconfirmed complete response, death from any cause; or additional treatment, whichever came first.
9 secondary outcomes
3 Years Progression-free Survival
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
3 Years Overall Survival
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Rate of Complete Remissions and Progressive Disease
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Number of Patients With a Relapse After a CR/CRu
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Safety (Adverse Events, Serious Adverse Events, Rate of Secondary Neoplasia, Selected Laboratory Parameters, Including Leucocytes, Thrombocytes, and Haemoglobin)
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Absolute Dose Vincristine and Prednisone in mg (Median)
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Health-economic Aspects - Number of Patients Who Received Antibiotic Intervention and/or Red Blood Cell and Platelet Transfusion
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Total Duration of Chemotherapy in Days (Median)
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Absolute Dose Cyclophosphamide, Doxorubicin and Rituximab in mg/m² (Median)
Time frame: Each patient will be observed for 3 years starting from completion of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationRadiotherapy (RT) to bulky (B) and extralymphatic (E) disease in combination with 6xR-CHOP-14 or R-CHOP-21 in young good-prognosis DLBCL patients: Results of the 2x2 randomized UNFOLDER trial of the DSHNHL/GLA. Michael Pfreundschuh, Niels Murawski, Marita Ziepert, Bettina Altmann, Martin H. Dreyling, Peter Borchmann, Stefano Luminari, Mathias Witzens-Harig, Judith Dierlamm, Mathias Haenel, Lorenz Truemper, Bernd Metzner, Eva Lengfelder, Ulrich B. Keller, Christian Ruebe, Christian Berdel, Norbert Schmitz, Gerhard Held, and Viola Poeschel Journal of Clinical Oncology 2018 36:15_suppl, 7574-7574
- Results publicationRole of radiotherapy and dose-densification of R-CHOP in primary mediastinal B-cell lymphoma: A subgroup analysis of the unfolder trial of the German Lymphoma Alliance (GLA). Gerhard Held, Lorenz Thurner, Viola Poeschel, Christian Berdel, German Ott, Christian Schmidt, Andreas Viardot, Peter Borchmann, Ofer Shpilberg, Maike Nickelsen, Massimo Federico, Peter de Nully Brown, Niels Murawski, Lorenz H. Trumper, Heinz Schmidberger, Christian Ruebe, Jochen Fleckenstein, Norbert Schmitz, Markus Loeffler, Marita Ziepert, and German Lymphoma Alliance Journal of Clinical Oncology 2020 38:15_suppl, 8041-8041
- Derived from this study: PubMed 37427146Thurner L, Ziepert M, Berdel C, Schmidt C, Borchmann P, Kaddu-Mulindwa D, Viardot A, Witzens-Harig M, Dierlamm J, Haenel M, Metzner B, Wulf G, Lengfelder E, Keller UB, Frickhofen N, Nickelsen M, Gaska T, Griesinger F, Mahlberg R, Marks R, Shpilberg O, Lindemann HW, Soekler M, Fischer von Weikersthal L, Kiehl M, Roemer E, Bentz M, Krammer-Steiner B, Trappe R, de Nully Brown P, Federico M, Merli F, Engelhard M, Glass B, Schmitz N, Truemper L, Bewarder M, Hartmann F, Murawski N, Stilgenbauer S, Rosenwald A, Altmann B, Schmidberger H, Fleckenstein J, Loeffler M, Poeschel V, Held G. Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study. Hemasphere. 2023 Jul 5;7(7):e904. doi: 10.1097/HS9.0000000000000904. eCollection 2023 Jul.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael G.M. Pfreundschuh, MD † study chair
Universitaetsklinikum des Saarlandes
Viola Poeschel, MD study director
Study Office Homburg
152 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing filgrastim, rituximab and cyclophosphamide in people with Lymphoma, run by German High-Grade Non-Hodgkin's Lymphoma Study Group at 152 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 152 sites in Germany, Italy, Denmark, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3 Years Event-free Survival (time frame: Each patient will be observed for 3 years starting from completion of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00278408, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2025.