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

Lymphoma Clinical Trial

Official title:

Randomised Trial Comparing Chemotherapy Mit CHOEP (Cyclophosphamid, Doxorubicin, Vincristin, Etoposid Und Prednison) In 21-Day Intervals In Standard And Escalated Doses In Patients Aged 18-60 Years Of Age With Aggresive Non-Hodgkin-Lymphomas Favourable Prognoses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00053768
• Other study ID #: CDR0000269371
• Secondary ID: DSHNHL-1999-2EU-
• Status: Completed
• Phase: Phase 3
• Start date: April 2002
• Est. completion date: December 5, 2006

Study information

• Verified date: May 2021
• Source: Universität des Saarlandes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: December 5, 2006
• Est. primary completion date: December 5, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma

• Previously untreated disease

• Favorable prognosis

• International Prognostic Index score of 0-1

• No more than 25% marrow involvement

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Performance status

• ECOG 0-3 OR

• Karnofsky 40-100%

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 100,000/mm^3

• WBC at least 2,500/mm^3

Hepatic

• No active hepatitis infection

Renal

• Not specified

Other

• HIV negative

• Not pregnant or nursing

• No relevant accompanying disease

• No other concurrent malignancy

• No contraindications to any study medications

• No prior noncompliance by patient

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No other concurrent participation in another treatment study

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim

Drug:
• EPOCH regimen

• cyclophosphamide

• doxorubicin hydrochloride

• etoposide

• prednisone

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Germany	Haematologisch Onkologische Praxis	Aachen
Germany	Klinikum St. Marien	Amberg
Germany	Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie	Ansbach
Germany	II. Medizinische Klinik	Aschaffenburg
Germany	Specialist Practice for Oncology	Aschaffenburg
Germany	Haematologische Praxis	Augsburg
Germany	Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg	Augsburg
Germany	Klinikum Augsburg	Augsburg
Germany	Kreiskrankenhaus Aurich	Aurich
Germany	Kreiskrankenhaus	Bad Hersfeld
Germany	Humaine - Clinic	Bad Saarow
Germany	Krankenhaus Hohe Warte Mediziniche Klinik	Bayreuth
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Onkolog - Haematolog Schwerpunktpraxis	Berlin
Germany	Hospital Complex Bernburg	Bernburg
Germany	Krankenhaus Bietigheim	Bietigheim
Germany	Saint Agnes Hospital	Bocholt
Germany	Knappschaft Krankenhaus	Bochum
Germany	Saint Josef Hospital	Bochum
Germany	Medizinische Poliklinik	Bonn
Germany	Rheinische Friedrich-Wilhelms-Universitat	Bonn
Germany	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen
Germany	Medizinische Klinik Am Lukas - Krankenhaus	Bunde
Germany	General Hospital	Celle
Germany	Hospital Kuchwald Chemnitz	Chemnitz
Germany	Carl - Thiem - Klinkum Cottbus	Cottbus
Germany	Klinikum Darmstadt	Darmstadt
Germany	Saint Johannes Hospital Dortmund	Dortmund
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth	Duesseldorf
Germany	St. Johannes Hospital - Medical Klinik II	Duisburg
Germany	Franz Hospital Dulmen	Dulmen
Germany	Hans - Susemihl - Krankenhaus	Emden
Germany	Klinikum Erfurt	Erfurt
Germany	St. Antonius Hospital	Eschweiler
Germany	Evangelisches Krankenhaus Essen-Werden	Essen
Germany	Universitaetsklinikum Essen	Essen
Germany	Krankenhaus Nordwest	Frankfurt
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt/Oder
Germany	Evang. Deaconess Hospital Freiburg	Freiburg
Germany	Municipal Hospital Complex	Fulda
Germany	Robert - Koch Hospital	Gehrden
Germany	Centre for Internal Medicine Gießen	Gießen
Germany	Universitaetsklinikum Göttingen	Göttingen
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Staedtisches Klinikum Guetersloh	Gutersloh
Germany	Allgemeines Krankenhaus Hagen	Hagen
Germany	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen
Germany	Krankenhaus Martha-Maria Halle-Doelau gGmbH	Halle
Germany	Universitaetsklinikum Halle	Halle
Germany	Krankenhaus St. Elisabeth und St. Barbara	Halle/Saale
Germany	Allgemeines Krankenhaus Altona	Hamburg
Germany	Asklepios Klinik Nord Heidberg	Hamburg
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Evangelische Krankenhaus Hamm	Hamm
Germany	Henriettenstiftung Krankenhaus	Hannover
Germany	Krankenhaus Siloah - Medizinische Klinik II	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Oncology Specialists Clinic	Harrislee
Germany	Medizinische Universitaetsklinik und Poliklinik	Heidelberg
Germany	Thoraxklinik Heidelberg	Heidelberg
Germany	Regional Hospital Heidenheim	Heidenheim
Germany	Regional Hospital Am Plattenwald - Bad Friedrichhall	Heilbronn
Germany	Klinikum Herford	Herford
Germany	Marienhospital at Ruhr University Bochum	Herne
Germany	Privatklinik Dr. R. Schindlbeck GmbH & Co. KG	Herrsching Am Ammersee
Germany	Onkologische Schwerpunktpraxis	Hildesheim
Germany	Evang. Hospital	Holzminden
Germany	Medical University Hospital Homburg	Homburg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Hospital Complex Hoyerswerda	Hoyerswerda
Germany	Gemeinschaftspraxis Innere Medizin	Jena
Germany	Klinikum der Friedrich-Schiller Universitaet Jena	Jena
Germany	Municipal Hospital Complex of the University	Kaiserslautern
Germany	Staedtisches Klinikum Karlsruhe gGmbH	Karlsruhe
Germany	Red Cross Hospital Kassel	Kassel
Germany	Staedtisches Krankenhaus Kiel	Kiel
Germany	Praxis fuer Haematologie und Onkologie	Koblenz
Germany	Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH	Koblenz
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Koln
Germany	Praxis Fuer Haematologie Internistische Onkologie	Koln
Germany	Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim	Koln-Merheim
Germany	Leonardis Clinic	Kornwestheim
Germany	Klinikum Krefeld GmbH	Krefeld
Germany	Frankenwald Klinik	Kronach
Germany	Caritas - Krakenhaus Lebach	Lebach
Germany	Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig	Leipzig
Germany	Staedtisches Klinikum "St. Georg" Leipzig	Leipzig
Germany	University Leipzig Clinic of Internal Medicine	Leipzig
Germany	Klinikum Lippe - Lemgo	Lemgo
Germany	St. Vincenz Hospital Limburg	Limburg
Germany	St. Bonifatius Hospital Lingen	Lingen
Germany	Dreifaltigkeits Hospital	Lippstadt
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Klinikum der Stadt Ludwigshafen am Rhein	Ludwigshafen
Germany	St. Marien Hospital Ludwighafen	Ludwigshafen
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Luebeck
Germany	Staedtisches Klinikum Magdeburg - Altstadt	Magdeburg
Germany	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	Johannes Gutenberg University	Mainz
Germany	German CML Study Group	Manheim
Germany	Philipps-Universitaet Marburg Klinikum	Marburg
Germany	Regional Hospital Mayen	Mayen
Germany	Klinikum Minden	Minden
Germany	Ev. Hospital Bethesda	Monchenglabach
Germany	Hospital Maria-Hilf II	Monchengladbach
Germany	Evangelisches Krankenhaus - Mülheim	Mülheim
Germany	St. Marien Hospital - Muelheim an der Ruhr	Mulheim/Ruhr
Germany	Kreiskrankenhaus Muenchberg	Munchberg
Germany	Klinikum der Universitaet Muenchen - Innenstadt Campus	Munchen
Germany	Munich Oncologic Practice at Elisenhof	Munchen
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
Germany	Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster	Munster
Germany	Regional Hospital Neumarkt	Neumarkt
Germany	Staedtisches Klinikum Neunkirchen gGmbH	Neunkirchen
Germany	Lukaskrankenhaus Neuss	Neuss
Germany	Klinikum Nuernberg - Klinikum Nord	Nurnberg
Germany	Klinikum Offenburg	Offenburg
Germany	Ev. Hospital Oldenburg	Oldenburg
Germany	Hematologische Praxis	Oldenburg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Paracelsus - Klinik Osnabrück	Osnabrück
Germany	Municipal Hospital Complex	Pforzheim
Germany	Klinikum Ernst Von Bergmann	Potsdam
Germany	Kreiskrankenhaus Radebeul	Radebeul
Germany	Krankenhaus St. Elisabeth - Ravensburg	Ravensburg
Germany	Hematologische Onkologische Praxis	Regensburg
Germany	Klinikum der Universitaet Regensburg	Regensburg
Germany	Krankenhaus Barmherzige Brueder Regensburg	Regensburg
Germany	Jakobi Krankenhaus	Rheine
Germany	Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock	Rostock
Germany	Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock	Rostock
Germany	Caritasklinik St. Theresia	Saarbrucken
Germany	Schwerpunktpraxis fuer Haematologie und Onkologie	Saarbrucken
Germany	St. Elizabeth-Klinik Saarlouis	Saarlouis
Germany	Martin - Luther Hospital	Schleswig
Germany	Deaconess Hospital	Schwabisch Hall
Germany	Leopoldina - Krankenhaus	Schweinfurt
Germany	Evang. Jung-Stilling Hospital	Siegen
Germany	St. Lukas - Clinic Solingen	Solingen
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Hospital Bad Cannstatt	Stuttgart
Germany	Klinik fuer Onkologie - Katharinenhospital Stuttgart	Stuttgart
Germany	Klinikum Stuttgart - Buergerhospital	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	St. Elisabeth Hospital Thuine	Thuine
Germany	Regional Hospital Traunstein	Traunstein
Germany	Krankenanstalt Mutterhaus der Borromaerinnen	Trier
Germany	Krankenhaus Der Barmherzigen Brueder	Trier
Germany	Hospital Tutzing	Tutzing
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	Ev. Hospital Unna	Unna
Germany	St. Marienhospital - Vechta	Vechta
Germany	Klinikum Der Stadt Villingen - Schwenningen	Villingen-Schwenningen
Germany	Regional Hospital Waldbrol	Waldbrol
Germany	Hospital Wetzler	Wetzlar
Germany	Deutsche Klinik fuer Diagnostik	Wiesbaden
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Ev. Hospital Witten-Herdecke	Witten
Germany	University Wurzburg	Wuerzburg
Germany	Kliniken St. Antonius	Wuppertal
Germany	Municipal Hospital Complex Zwickau	Zwickau
Switzerland	City Hospital Triemli	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
German High-Grade Non-Hodgkin's Lymphoma Study Group

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (2)

Pfreundschuh M, Zwick C, Zeynalova S, Dührsen U, Pflüger KH, Vrieling T, Mesters R, Mergenthaler HG, Einsele H, Bentz M, Lengfelder E, Trümper L, Rübe C, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Dose-escalated — View Citation

Trümper L, Zwick C, Ziepert M, Hohloch K, Schmits R, Mohren M, Liersch R, Bentz M, Graeven U, Wruck U, Hoffmann M, Metzner B, Hasenclever D, Loeffler M, Pfreundschuh M; German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: I. A randomized dose escalation and feasibility study with bi- and tri-weekly regimens. Ann Oncol. 2008 Mar;19(3):538-44. doi: 10.1093/annonc/mdm497. Epub 2008 Jan 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to treatment failure (TTF) at first relapse	Time to Treatment failure using the Kaplan_Meier-Method	3 years within study and periodically after study completion
Secondary	Complete response rate at first relapse	Number of complete remission (CR) and unconfirmed complete Remission (CRu)	3 years within study and periodically after study completion
Secondary	Survival time	Time till death (whatever cause)	3 years within study and periodically after study completion
Secondary	Tumor control	Calcution of treatment Duration using the Kaplan-Meier method	thought the treatment
Secondary	Disease-free survival	Time of disease-free survivial	3 years within study and periodically after study completion