MedPath

Rituximab and Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma

Phase 3
Completed
Conditions
Lymphoma
Interventions
Registration Number
NCT00278421
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, 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. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which schedule of rituximab and combination chemotherapy is more effective in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

Primary

* Compare the efficacy of 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in patients with previously untreated, low-risk, aggressive B-cell non-Hodgkin's lymphoma.

* Compare acute and chronic side effects in patients treated with these regimens.

* Compare time to treatment failure in patients treated with these regimens.

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 participating center. Patients are randomized to 1 of 2 treatment arms.

All patients are 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: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.

* Arm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.

All patients undergo final restaging after 6 courses of rituximab. Patients with disease progression, stable disease, or partial response proceed to salvage therapy off study.

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

PROJECTED ACCRUAL: A total of 622 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
592
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Interventional: 6 R-CHOP-21vincristine sulfateArm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
Interventional: 4 R-CHOP-21 + 2 x RrituximabArm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
Interventional: 6 R-CHOP-21rituximabArm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
Interventional: 4 R-CHOP-21 + 2 x Rvincristine sulfateArm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
Interventional: 6 R-CHOP-21cyclophosphamideArm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
Interventional: 6 R-CHOP-21doxorubicin hydrochlorideArm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
Interventional: 6 R-CHOP-21prednisoneArm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
Interventional: 4 R-CHOP-21 + 2 x RcyclophosphamideArm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
Interventional: 4 R-CHOP-21 + 2 x Rdoxorubicin hydrochlorideArm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
Interventional: 4 R-CHOP-21 + 2 x RprednisoneArm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.
Primary Outcome Measures
NameTimeMethod
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-upthrough study completion
Secondary Outcome Measures
NameTimeMethod
Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored)through study completion
Disease-free survival measured from day 1 of course 1 of CHOP therapythrough study completion
Safety (adverse events, serious adverse events) assessed at 3 months after treatmentthrough study completion
Complete response (CR) rate duration until first relapsethrough study completion
Progression rate during treatmentthrough study completion
Survivalthrough study completion

Trial Locations

Locations (76)

Klinikum Lippe - Lemgo

🇩🇪

Lemgo, Germany

Onkologische Schwerpunktpraxis

🇩🇪

Wendlingen, Germany

Klinikum Frankfurt (Oder) GmbH

🇩🇪

Frankfurt (Oder), Germany

Haematologisch Onkologische Praxis

🇩🇪

Aachen, Germany

Klinikum Fulda

🇩🇪

Fulda, Germany

Saint Josef Hospital

🇩🇪

Gelsenkirchen, Germany

Kreiskrankenhaus Gummersbach GMBH

🇩🇪

Gummersbach, Germany

Medizinische Universitaetsklinik I at the University of Cologne

🇩🇪

Cologne, Germany

Klinikum Dortmund

🇩🇪

Dortmund, Germany

St. Antonius Hospital

🇩🇪

Eschweiler, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Clinic for Bone Marrow Transplantation and Hematology and Oncology

🇩🇪

Idar-Oberstein, Germany

Haematologisch-Onkologische Praxis Altona

🇩🇪

Hamburg, Germany

Universitaetsklinikum Essen

🇩🇪

Essen, Germany

Universitaetsklinikum Freiburg

🇩🇪

Freiburg, Germany

St. Bernward Krankenhaus

🇩🇪

Hildesheim, Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

🇩🇪

Munich, Germany

Universitaetsklinikum Goettingen

🇩🇪

Goettingen, Germany

Evangelische Krankenhaus Hamm

🇩🇪

Hamm, Germany

St. Marien-Hospital Hamm - Klinik Knappenstrasse

🇩🇪

Hamm, Germany

University Medical Center Hamburg - Eppendorf

🇩🇪

Hamburg, Germany

Ruprecht - Karls - Universitaet Heidelberg

🇩🇪

Heidelberg, Germany

Universitaetsklinikum des Saarlandes

🇩🇪

Homburg, Germany

Krankenhaus Ludmillenstift

🇩🇪

Meppen, Germany

Staedtisches Klinikum Karlsruhe gGmbH

🇩🇪

Karlsruhe, Germany

Klinikum Kempten Oberallgaeu

🇩🇪

Kempten, Germany

University Hospital Schleswig-Holstein - Kiel Campus

🇩🇪

Kiel, Germany

St. Vincenz Hospital Limburg

🇩🇪

Limburg, Germany

St. Vincentius - Kliniken

🇩🇪

Karlsruhe, Germany

Klinikum der Stadt Ludwigshafen am Rhein

🇩🇪

Ludwigshafen am Rhein, Germany

Prosper-Hospital Recklinghausen

🇩🇪

Recklinghausen, Germany

III Medizinische Klinik Mannheim

🇩🇪

Mannheim, Germany

Southwest German Cancer Center at Eberhard-Karls-University

🇩🇪

Tuebingen, Germany

Helios Kliniken Wuppertal University Hospital

🇩🇪

Wuppertal, Germany

Klinikum Schwaebisch Gmuend Stauferklinik

🇩🇪

Mutlangen, Germany

Klinikum Ernst Von Bergmann

🇩🇪

Potsdam, Germany

Diakonie Klinikum Stuttgart

🇩🇪

Stuttgart, Germany

Krankenanstalt Mutterhaus der Borromaerinnen

🇩🇪

Trier, Germany

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

🇩🇪

Ulm, Germany

Dr. Horst-Schmidt-Kliniken

🇩🇪

Wiesbaden, Germany

Onkologische Schwerwpunktpraxis Dr. Ladda

🇩🇪

Neumarkt, Germany

Klinikum Oldenburg

🇩🇪

Oldenburg, Germany

Ospedale Civile - Piacenza

🇮🇹

Piacenza, Italy

St. Marien - Krankenhaus Siegen GMBH

🇩🇪

Siegen, Germany

St. Marienhospital - Vechta

🇩🇪

Vechta, Germany

Rabin Medical Center - Beilinson Campus

🇮🇱

Petah-Tikva, Israel

Arcispedale S. Maria Nuova

🇮🇹

Reggio Emilia, Italy

Haematologisch-Onkologische Schwerpunktpraxis - Weilheim

🇩🇪

Berlin, Germany

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

🇩🇪

Berlin, Germany

St. Sixtus Hospital

🇩🇪

Haltern, Germany

Klinikum Augsburg

🇩🇪

Augsburg, Germany

Klinikum Bayreuth

🇩🇪

Bayreuth, Germany

Caritas - Krakenhaus Lebach

🇩🇪

Lebach, Germany

Franziskus Hospital

🇩🇪

Bielefeld, Germany

DIAKO Ev. Diakonie Krankenhaus gGmbH

🇩🇪

Bremen, Germany

Hospital Kuchwald Chemnitz

🇩🇪

Chemnitz, Germany

Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke

🇩🇪

Damme, Germany

Augusta-Kranken-Anstalt gGmbH

🇩🇪

Bochum, Germany

Staedtisches Klinikum Braunschweig

🇩🇪

Braunschweig, Germany

Carl - Thiem - Klinkum Cottbus

🇩🇪

Cottbus, Germany

Praxis Fuer Haematologie Internistische Onkologie

🇩🇪

Cologne, Germany

Hans - Susemihl - Krankenhaus

🇩🇪

Emden, Germany

Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

🇩🇪

Greifswald, Germany

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

🇩🇪

Hagen, Germany

Asklepios Klinik St. Georg

🇩🇪

Hamburg, Germany

Kreiskrankenhaus Luedenscheid

🇩🇪

Luedenscheid, Germany

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

🇩🇪

Magdeburg, Germany

Universitaetsklinikum Giessen und Marburg GmbH - Marburg

🇩🇪

Marburg, Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

🇩🇪

Munich, Germany

Lukaskrankenhaus Neuss

🇩🇪

Neuss, Germany

Schlossbergkliniken Oberstaufen

🇩🇪

Oberstaufen, Germany

Krankenhaus Maria Hilf GmbH

🇩🇪

Moenchengladbach, Germany

Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

🇩🇪

Muenster, Germany

Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster

🇩🇪

Muenster, Germany

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

Cellulari ed Ematologia Sapienza

🇮🇹

Roma, Italy

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