Rituximab and Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabBiological: filgrastimRadiation: radiation therapy
- Registration Number
- NCT00278408
- Lead Sponsor
- German High-Grade Non-Hodgkin's Lymphoma Study Group
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 700
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Interventional: 6 R-CHOP-21 rituximab 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. Interventional: 6 R-CHOP-21 vincristine sulfate 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. Interventional: 6 R-CHOP-21 + radiotherapy rituximab 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. Interventional: 6 R-CHOP-21 + radiotherapy vincristine sulfate 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. Interventional: 6 R-CHOP-21 + radiotherapy radiation therapy 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. Interventional: 6 R-CHOP-14 filgrastim 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. Interventional: 6 R-CHOP-14 rituximab 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. Interventional: 6 R-CHOP-14 vincristine sulfate 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. Interventional: 6 R-CHOP-14 and radiotherapy filgrastim 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. Interventional: 6 R-CHOP-14 and radiotherapy rituximab 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. Interventional: 6 R-CHOP-14 and radiotherapy vincristine sulfate 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. Interventional: 6 R-CHOP-14 and radiotherapy radiation therapy 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. Interventional: 6 R-CHOP-21 cyclophosphamide 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. Interventional: 6 R-CHOP-21 doxorubicin hydrochloride 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. Interventional: 6 R-CHOP-21 + radiotherapy cyclophosphamide 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. Interventional: 6 R-CHOP-21 prednisone 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. Interventional: 6 R-CHOP-21 + radiotherapy doxorubicin hydrochloride 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. Interventional: 6 R-CHOP-21 + radiotherapy prednisone 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. Interventional: 6 R-CHOP-14 cyclophosphamide 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. Interventional: 6 R-CHOP-14 doxorubicin hydrochloride 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. Interventional: 6 R-CHOP-14 prednisone 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. Interventional: 6 R-CHOP-14 and radiotherapy cyclophosphamide 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. Interventional: 6 R-CHOP-14 and radiotherapy doxorubicin hydrochloride 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. Interventional: 6 R-CHOP-14 and radiotherapy prednisone 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.
- Primary Outcome Measures
Name Time Method 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 3 years
- Secondary Outcome Measures
Name Time Method Complete response (CR) rate until first relapse through study completion Progression rate during treatment 3 years Survival through study completion Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored) 3 years Disease-free survival measured from day 1 of course 1 of CHOP therapy life-long Relapse-free survival of patients with complete response (CR) or unconfirmed complete response (CRu) following complete immunochemotherapy through study completion Safety (adverse events, serious adverse events) assessed at 3 months after completion of study treatment 3 years Consolidating radiotherapy 3 years
Trial Locations
- Locations (79)
Virngrund-Klinik Ellwangen
🇩🇪Ellwangen, Germany
Klinikum Bayreuth
🇩🇪Bayreuth, Germany
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, Germany
Universitaetsklinikum Goettingen
🇩🇪Goettingen, Germany
Klinikum Kempten Oberallgaeu
🇩🇪Kempten, Germany
Charite - Campus Charite Mitte
🇩🇪Berlin, Germany
Franziskus Hospital
🇩🇪Bielefeld, Germany
Charite University Hospital - Campus Virchow Klinikum
🇩🇪Berlin, Germany
Staedtisches Klinikum Braunschweig
🇩🇪Braunschweig, Germany
Onkologische Schwerpunktpraxis Celle
🇩🇪Celle, Germany
Klinikum Dortmund
🇩🇪Dortmund, Germany
Krankenhaus Nordwest
🇩🇪Frankfurt, Germany
Klinikum Frankfurt (Oder) GmbH
🇩🇪Frankfurt (Oder), Germany
Klinikum Garmisch - Partenkirchen GmbH
🇩🇪Garmisch-Partenkirchen, Germany
Saint Josef Hospital
🇩🇪Gelsenkirchen, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Krankenhaus Siloah - Medizinische Klinik II
🇩🇪Hannover, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
Klinikum der Stadt Ludwigshafen am Rhein
🇩🇪Ludwigshafen am Rhein, Germany
Medizinische Universitaetsklinik und Poliklinik
🇩🇪Heidelberg, Germany
Universitaetsklinikum des Saarlandes
🇩🇪Homburg, Germany
Onkologische Schwerpunktpraxis - Straubing
🇩🇪Straubing, Germany
Praxis Fuer Internistische Haematologie / Onkologie
🇩🇪Troisdorf, Germany
Krankenhaus Maria Hilf GmbH
🇩🇪Moenchengladbach, Germany
Regional Hospital Waldbrol
🇩🇪Waldbrol, Germany
III Medizinische Klinik Mannheim
🇩🇪Mannheim, Germany
Klinikum Minden
🇩🇪Minden, Germany
Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
🇩🇪Muenster, Germany
Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Bruederkrankenhaus St. Josef Paderborn
🇩🇪Paderborn, Germany
Rabin Medical Center - Beilinson Campus
🇮🇱Petah-Tikva, Israel
Krankenanstalt Mutterhaus der Borromaerinnen
🇩🇪Trier, Germany
Krankenhaus Der Barmherzigen Brueder
🇩🇪Trier, Germany
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Dr. Horst-Schmidt-Kliniken
🇩🇪Wiesbaden, Germany
Heinrich-Braun-Krankenhaus Zwickau
🇩🇪Zwickau, Germany
Klinikum Bremen-Mitte
🇩🇪Bremen, Germany
Hans - Susemihl - Krankenhaus
🇩🇪Emden, Germany
St. Antonius Hospital
🇩🇪Eschweiler, Germany
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
🇩🇪Greifswald, Germany
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
🇩🇪Hagen, Germany
Krankenhaus Martha-Maria Halle-Doelau gGmbH
🇩🇪Halle, Germany
University Medical Center Hamburg - Eppendorf
🇩🇪Hamburg, Germany
Klinikum Stadt Hanau
🇩🇪Hanau, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Staedtisches Krankenhaus Kiel
🇩🇪Kiel, Germany
Internistische Praxis - Landshut
🇩🇪Landshut, Germany
Kreiskrankenhaus Luedenscheid
🇩🇪Luedenscheid, Germany
Klinikum der Universitaet Muenchen - Grosshadern Campus
🇩🇪Munich, Germany
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
🇩🇪Munich, Germany
Onkologische Schwerwpunktpraxis Dr. Ladda
🇩🇪Neumarkt, Germany
Klinikum der Universitaet Regensburg
🇩🇪Regensburg, Germany
Klinikum Suedstadt Rostock
🇩🇪Rostock, Germany
Leopoldina - Krankenhaus
🇩🇪Schwienfurt, Germany
St. Marien - Krankenhaus Siegen GMBH
🇩🇪Siegen, Germany
Klinik fuer Onkologie - Katharinenhospital Stuttgart
🇩🇪Stuttgart, Germany
Diakonie Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Kliniken St. Antonius
🇩🇪Wuppertal 2, Germany
Kreiskrankenhaus Aurich
🇩🇪Aurich, Germany
Klinikum St. Marien
🇩🇪Amberg, Germany
Klinikum Augsburg
🇩🇪Augsburg, Germany
Augusta-Kranken-Anstalt gGmbH
🇩🇪Bochum, Germany
Hospital Kuchwald Chemnitz
🇩🇪Chemnitz, Germany
Praxis Fuer Haematologie Internistische Onkologie
🇩🇪Cologne, Germany
Medizinische Universitaetsklinik I at the University of Cologne
🇩🇪Cologne, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Carl - Thiem - Klinkum Cottbus
🇩🇪Cottbus, Germany
Wilhelm-Anton-Hospital gGmbH, Goch
🇩🇪Goch, Germany
Haematologie und Internistische Onkologie Praxis
🇩🇪Homberg, Germany
Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
🇩🇪Herrsching, Germany
Clinic for Bone Marrow Transplantation and Hematology and Oncology
🇩🇪Idar-Oberstein, Germany
Staedtisches Klinikum Karlsruhe gGmbH
🇩🇪Karlsruhe, Germany
Internistische Gemeinschaftspraxis - Kassel
🇩🇪Kassel, Germany
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
🇩🇪Magdeburg, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Praxis fuer Haematologie und Onkologie
🇩🇪Twistringen, Germany
St. Marienhospital - Vechta
🇩🇪Vechta, Germany
St. Bernward Krankenhaus
🇩🇪Hildesheim, Germany