MedPath

Combination Chemotherapy Followed By Radiation Therapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

Phase 3
Completed
Conditions
Lymphoma
Interventions
Registration Number
NCT00053768
Lead Sponsor
German High-Grade Non-Hodgkin's Lymphoma Study Group
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and giving the drugs in different ways may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known which combination chemotherapy regimen followed by radiation therapy is more effective in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens followed by radiation therapy to compare how well they work in treating patients with aggressive non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

* Compare the efficacy of standard-dose vs high-dose cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone followed by radiotherapy, in terms of time to treatment failure, in patients with aggressive non-Hodgkin's lymphoma.

* Compare the acute and long-term toxic effects of these regimens in these patients.

* Compare the complete response rate, survival and tumor control, and disease-free survival in patients treated with these regimens.

* Analyze the time to relapse after radiotherapy in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to LDH levels (no greater than upper limit of normal \[ULN\] vs greater than ULN), initial bulky disease (yes vs no), stage (I or II vs II or IV), ECOG performance status (0 or 1 vs 2 or 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:

* Arm I (Standard dose): Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5 (CHOEP) in standard doses.

* Arm II (Escalated dose): Patients receive high-dose CHOEP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously on days 6-12.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of CHOEP chemotherapy, patients with initial bulky disease or extranodal involvement undergo radiotherapy 5 days a week for 4 weeks.

Patients who undergo radiotherapy are followed at 2 months after radiotherapy. All patients (including those who undergo radiotherapy) are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 389 patients were accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
392
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
high CHOEP-21vincristine sulfateHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21EPOCH regimenCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21filgrastimCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21EPOCH regimenHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21radiation therapyHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21vincristine sulfateCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21radiation therapyCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21filgrastimHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21doxorubicin hydrochlorideCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21cyclophosphamideCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21etoposideCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
CHOEP-21prednisoneCHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21cyclophosphamideHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21doxorubicin hydrochlorideHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21prednisoneHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
high CHOEP-21etoposideHigh-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)
Primary Outcome Measures
NameTimeMethod
Time to treatment failure (TTF) at first relapse3 years within study and periodically after study completion

Time to Treatment failure using the Kaplan_Meier-Method

Secondary Outcome Measures
NameTimeMethod
Tumor controlthought the treatment

Calcution of treatment Duration using the Kaplan-Meier method

Complete response rate at first relapse3 years within study and periodically after study completion

Number of complete remission (CR) and unconfirmed complete Remission (CRu)

Survival time3 years within study and periodically after study completion

Time till death (whatever cause)

Disease-free survival3 years within study and periodically after study completion

Time of disease-free survivial

Trial Locations

Locations (165)

Regional Hospital Traunstein

🇩🇪

Traunstein, Germany

Hospital Tutzing

🇩🇪

Tutzing, Germany

Krankenhaus Der Barmherzigen Brueder

🇩🇪

Trier, Germany

St. Marienhospital - Vechta

🇩🇪

Vechta, Germany

Klinikum Stuttgart - Buergerhospital

🇩🇪

Stuttgart, Germany

St. Elisabeth Hospital Thuine

🇩🇪

Thuine, Germany

Hospital Bad Cannstatt

🇩🇪

Stuttgart, Germany

Robert-Bosch-Krankenhaus

🇩🇪

Stuttgart, Germany

Municipal Hospital Complex Zwickau

🇩🇪

Zwickau, Germany

Hospital Wetzler

🇩🇪

Wetzlar, Germany

Ev. Hospital Unna

🇩🇪

Unna, Germany

Klinikum Der Stadt Villingen - Schwenningen

🇩🇪

Villingen-Schwenningen, Germany

Saint Josef Hospital

🇩🇪

Bochum, Germany

Medizinische Poliklinik

🇩🇪

Bonn, Germany

Klinikum Augsburg

🇩🇪

Augsburg, Germany

Rheinische Friedrich-Wilhelms-Universitat

🇩🇪

Bonn, Germany

Haematologisch Onkologische Praxis

🇩🇪

Aachen, Germany

Kreiskrankenhaus

🇩🇪

Bad Hersfeld, Germany

Robert - Koch Hospital

🇩🇪

Gehrden, Germany

General Hospital

🇩🇪

Celle, Germany

Charite - Campus Charite Mitte

🇩🇪

Berlin, Germany

Hans - Susemihl - Krankenhaus

🇩🇪

Emden, Germany

II. Medizinische Klinik

🇩🇪

Aschaffenburg, Germany

DIAKO Ev. Diakonie Krankenhaus gGmbH

🇩🇪

Bremen, Germany

Franz Hospital Dulmen

🇩🇪

Dulmen, Germany

Specialist Practice for Oncology

🇩🇪

Aschaffenburg, Germany

Knappschaft Krankenhaus

🇩🇪

Bochum, Germany

Saint Johannes Hospital Dortmund

🇩🇪

Dortmund, Germany

Humaine - Clinic

🇩🇪

Bad Saarow, Germany

Hospital Complex Bernburg

🇩🇪

Bernburg, Germany

Klinikum St. Marien

🇩🇪

Amberg, Germany

Haematologische Praxis

🇩🇪

Augsburg, Germany

Klinikum Darmstadt

🇩🇪

Darmstadt, Germany

St. Johannes Hospital - Medical Klinik II

🇩🇪

Duisburg, Germany

Onkolog - Haematolog Schwerpunktpraxis

🇩🇪

Berlin, Germany

Universitatsklinikum Carl Gustav Carus

🇩🇪

Dresden, Germany

Staedtisches Klinikum Guetersloh

🇩🇪

Gutersloh, Germany

Hospital Kuchwald Chemnitz

🇩🇪

Chemnitz, Germany

Allgemeines Krankenhaus Altona

🇩🇪

Hamburg, Germany

Thoraxklinik Heidelberg

🇩🇪

Heidelberg, Germany

Krankenhaus Siloah - Medizinische Klinik II

🇩🇪

Hannover, Germany

Regional Hospital Am Plattenwald - Bad Friedrichhall

🇩🇪

Heilbronn, Germany

Staedtisches Klinikum Karlsruhe gGmbH

🇩🇪

Karlsruhe, Germany

Leonardis Clinic

🇩🇪

Kornwestheim, Germany

Red Cross Hospital Kassel

🇩🇪

Kassel, Germany

Klinikum der Stadt Ludwigshafen am Rhein

🇩🇪

Ludwigshafen, Germany

Klinik fuer Onkologie - Katharinenhospital Stuttgart

🇩🇪

Stuttgart, Germany

Johannes Gutenberg University

🇩🇪

Mainz, Germany

Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie

🇩🇪

Ansbach, Germany

Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg

🇩🇪

Augsburg, Germany

Kreiskrankenhaus Aurich

🇩🇪

Aurich, Germany

Krankenhaus Hohe Warte Mediziniche Klinik

🇩🇪

Bayreuth, Germany

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

🇩🇪

Greifswald, Germany

Evangelische Krankenhaus Hamm

🇩🇪

Hamm, Germany

Oncology Specialists Clinic

🇩🇪

Harrislee, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Onkologische Schwerpunktpraxis

🇩🇪

Hildesheim, Germany

Evang. Hospital

🇩🇪

Holzminden, Germany

Hospital Complex Hoyerswerda

🇩🇪

Hoyerswerda, Germany

Gemeinschaftspraxis Innere Medizin

🇩🇪

Jena, Germany

Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig

🇩🇪

Leipzig, Germany

Klinikum Ludwigsburg

🇩🇪

Ludwigsburg, Germany

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

🇩🇪

Magdeburg, Germany

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

🇩🇪

Luebeck, Germany

Klinikum Minden

🇩🇪

Minden, Germany

Klinikum der Universitaet Muenchen - Innenstadt Campus

🇩🇪

Munchen, Germany

Munich Oncologic Practice at Elisenhof

🇩🇪

Munchen, Germany

Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster

🇩🇪

Munster, Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

🇩🇪

Munich, Germany

Krankenhaus Muenchen Schwabing

🇩🇪

Munich, Germany

Evangelisches Krankenhaus - Mülheim

🇩🇪

Mülheim, Germany

Lukaskrankenhaus Neuss

🇩🇪

Neuss, Germany

Regional Hospital Neumarkt

🇩🇪

Neumarkt, Germany

Staedtisches Klinikum Neunkirchen gGmbH

🇩🇪

Neunkirchen, Germany

Klinikum Nuernberg - Klinikum Nord

🇩🇪

Nurnberg, Germany

Klinikum Offenburg

🇩🇪

Offenburg, Germany

Hematologische Praxis

🇩🇪

Oldenburg, Germany

Krankenhaus St. Elisabeth - Ravensburg

🇩🇪

Ravensburg, Germany

Hematologische Onkologische Praxis

🇩🇪

Regensburg, Germany

Ev. Hospital Oldenburg

🇩🇪

Oldenburg, Germany

Klinikum Oldenburg

🇩🇪

Oldenburg, Germany

Paracelsus - Klinik Osnabrück

🇩🇪

Osnabrück, Germany

Klinikum Ernst Von Bergmann

🇩🇪

Potsdam, Germany

Klinikum der Universitaet Regensburg

🇩🇪

Regensburg, Germany

Krankenhaus Barmherzige Brueder Regensburg

🇩🇪

Regensburg, Germany

Jakobi Krankenhaus

🇩🇪

Rheine, Germany

Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock

🇩🇪

Rostock, Germany

Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock

🇩🇪

Rostock, Germany

Caritasklinik St. Theresia

🇩🇪

Saarbrucken, Germany

St. Elizabeth-Klinik Saarlouis

🇩🇪

Saarlouis, Germany

Martin - Luther Hospital

🇩🇪

Schleswig, Germany

Evang. Jung-Stilling Hospital

🇩🇪

Siegen, Germany

Deaconess Hospital

🇩🇪

Schwabisch Hall, Germany

Leopoldina - Krankenhaus

🇩🇪

Schweinfurt, Germany

St. Lukas - Clinic Solingen

🇩🇪

Solingen, Germany

Deutsche Klinik fuer Diagnostik

🇩🇪

Wiesbaden, Germany

Dr. Horst-Schmidt-Kliniken

🇩🇪

Wiesbaden, Germany

Ev. Hospital Witten-Herdecke

🇩🇪

Witten, Germany

Kliniken St. Antonius

🇩🇪

Wuppertal, Germany

UniversitaetsSpital Zuerich

🇨🇭

Zurich, Switzerland

City Hospital Triemli

🇨🇭

Zurich, Switzerland

Krankenhaus Bietigheim

🇩🇪

Bietigheim, Germany

Saint Agnes Hospital

🇩🇪

Bocholt, Germany

Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth

🇩🇪

Duesseldorf, Germany

Medizinische Klinik Am Lukas - Krankenhaus

🇩🇪

Bunde, Germany

Carl - Thiem - Klinkum Cottbus

🇩🇪

Cottbus, Germany

Klinikum Erfurt

🇩🇪

Erfurt, Germany

St. Antonius Hospital

🇩🇪

Eschweiler, Germany

Universitaetsklinikum Essen

🇩🇪

Essen, Germany

Evangelisches Krankenhaus Essen-Werden

🇩🇪

Essen, Germany

Klinikum Frankfurt (Oder) GmbH

🇩🇪

Frankfurt/Oder, Germany

Evang. Deaconess Hospital Freiburg

🇩🇪

Freiburg, Germany

Krankenhaus Nordwest

🇩🇪

Frankfurt, Germany

Municipal Hospital Complex

🇩🇪

Pforzheim, Germany

Universitaetsklinikum Göttingen

🇩🇪

Göttingen, Germany

Centre for Internal Medicine Gießen

🇩🇪

Gießen, Germany

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

🇩🇪

Hagen, Germany

Klinikum Herford

🇩🇪

Herford, Germany

Krankenhaus Martha-Maria Halle-Doelau gGmbH

🇩🇪

Halle, Germany

Universitaetsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

Allgemeines Krankenhaus Hagen

🇩🇪

Hagen, Germany

Krankenhaus St. Elisabeth und St. Barbara

🇩🇪

Halle/Saale, Germany

Henriettenstiftung Krankenhaus

🇩🇪

Hannover, Germany

Haematologisch-Onkologische Praxis Altona

🇩🇪

Hamburg, Germany

Universitaetsklinikum Halle

🇩🇪

Halle, Germany

Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim

🇩🇪

Koln-Merheim, Germany

Praxis Fuer Haematologie Internistische Onkologie

🇩🇪

Koln, Germany

Medizinische Universitaetsklinik I at the University of Cologne

🇩🇪

Koln, Germany

St. Vincenz Hospital Limburg

🇩🇪

Limburg, Germany

Klinikum Lippe - Lemgo

🇩🇪

Lemgo, Germany

Frankenwald Klinik

🇩🇪

Kronach, Germany

Asklepios Klinik Nord Heidberg

🇩🇪

Hamburg, Germany

Regional Hospital Heidenheim

🇩🇪

Heidenheim, Germany

Marienhospital at Ruhr University Bochum

🇩🇪

Herne, Germany

Privatklinik Dr. R. Schindlbeck GmbH & Co. KG

🇩🇪

Herrsching Am Ammersee, Germany

Klinikum der Friedrich-Schiller Universitaet Jena

🇩🇪

Jena, Germany

Municipal Hospital Complex of the University

🇩🇪

Kaiserslautern, Germany

Staedtisches Krankenhaus Kiel

🇩🇪

Kiel, Germany

Praxis fuer Haematologie und Onkologie

🇩🇪

Koblenz, Germany

Klinikum Krefeld GmbH

🇩🇪

Krefeld, Germany

Caritas - Krakenhaus Lebach

🇩🇪

Lebach, Germany

University Leipzig Clinic of Internal Medicine

🇩🇪

Leipzig, Germany

Medizinische Universitaetsklinik und Poliklinik

🇩🇪

Heidelberg, Germany

Krankenanstalt Mutterhaus der Borromaerinnen

🇩🇪

Trier, Germany

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

🇩🇪

Ulm, Germany

Medical University Hospital Homburg

🇩🇪

Homburg, Germany

Universitaetsklinikum des Saarlandes

🇩🇪

Homburg, Germany

German CML Study Group

🇩🇪

Manheim, Germany

Staedtisches Klinikum Magdeburg - Altstadt

🇩🇪

Magdeburg, Germany

St. Marien Hospital Ludwighafen

🇩🇪

Ludwigshafen, Germany

Philipps-Universitaet Marburg Klinikum

🇩🇪

Marburg, Germany

Regional Hospital Mayen

🇩🇪

Mayen, Germany

Ev. Hospital Bethesda

🇩🇪

Monchenglabach, Germany

Hospital Maria-Hilf II

🇩🇪

Monchengladbach, Germany

St. Marien Hospital - Muelheim an der Ruhr

🇩🇪

Mulheim/Ruhr, Germany

Kreiskrankenhaus Muenchberg

🇩🇪

Munchberg, Germany

Schwerpunktpraxis fuer Haematologie und Onkologie

🇩🇪

Saarbrucken, Germany

Diakonie Klinikum Stuttgart

🇩🇪

Stuttgart, Germany

Regional Hospital Waldbrol

🇩🇪

Waldbrol, Germany

University Wurzburg

🇩🇪

Wuerzburg, Germany

Dreifaltigkeits Hospital

🇩🇪

Lippstadt, Germany

Staedtisches Klinikum "St. Georg" Leipzig

🇩🇪

Leipzig, Germany

Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH

🇩🇪

Koblenz, Germany

St. Bonifatius Hospital Lingen

🇩🇪

Lingen, Germany

Kreiskrankenhaus Radebeul

🇩🇪

Radebeul, Germany

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