Clinical trial NCT00053768: Combination Chemotherapy Followed By Radiation Therapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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 mixed cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage I adult diffuse large cell lymphoma
stage I adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage I adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2003-02-06
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to treatment failure (TTF) at first relapse
timeFrame: 3 years within study and periodically after study completion
Secondary outcomes:
measure: Complete response rate at first relapse
timeFrame: 3 years within study and periodically after study completion
measure: Survival time
timeFrame: 3 years within study and periodically after study completion
measure: Tumor control
timeFrame: thought the treatment
measure: Disease-free survival
timeFrame: 3 years within study and periodically after study completion
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Haematologisch Onkologische Praxis
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Ansbach
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
city: Aschaffenburg
country: Germany
facility: Specialist Practice for Oncology
city: Aschaffenburg
country: Germany
facility: II. Medizinische Klinik
city: Augsburg
country: Germany
facility: Haematologische Praxis
city: Augsburg
country: Germany
facility: Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Aurich
country: Germany
facility: Kreiskrankenhaus Aurich
city: Bad Hersfeld
country: Germany
facility: Kreiskrankenhaus
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Bayreuth
country: Germany
facility: Krankenhaus Hohe Warte Mediziniche Klinik
city: Berlin
country: Germany
facility: Onkolog - Haematolog Schwerpunktpraxis
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Bernburg
country: Germany
facility: Hospital Complex Bernburg
city: Bietigheim
country: Germany
facility: Krankenhaus Bietigheim
city: Bocholt
country: Germany
facility: Saint Agnes Hospital
city: Bochum
country: Germany
facility: Saint Josef Hospital
city: Bochum
country: Germany
facility: Knappschaft Krankenhaus
city: Bonn
country: Germany
facility: Medizinische Poliklinik
city: Bonn
country: Germany
facility: Rheinische Friedrich-Wilhelms-Universitat
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Bunde
country: Germany
facility: Medizinische Klinik Am Lukas - Krankenhaus
city: Celle
country: Germany
facility: General Hospital
city: Chemnitz
country: Germany
facility: Hospital Kuchwald Chemnitz
city: Cologne-Kalk
country: Germany
city: Cottbus
country: Germany
facility: Carl - Thiem - Klinkum Cottbus
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dortmund
country: Germany
facility: Saint Johannes Hospital Dortmund
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth
city: Duisburg
country: Germany
facility: St. Johannes Hospital - Medical Klinik II
city: Dulmen
country: Germany
facility: Franz Hospital Dulmen
city: Emden
country: Germany
facility: Hans - Susemihl - Krankenhaus
city: Erfurt
country: Germany
facility: Klinikum Erfurt
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Essen
country: Germany
facility: Evangelisches Krankenhaus Essen-Werden
city: Frankfurt/Oder
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Freiburg
country: Germany
facility: Evang. Deaconess Hospital Freiburg
city: Fulda
country: Germany
facility: Municipal Hospital Complex
city: Gehrden
country: Germany
facility: Robert - Koch Hospital
city: Gießen
country: Germany
facility: Centre for Internal Medicine Gießen
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Gutersloh
country: Germany
facility: Staedtisches Klinikum Guetersloh
city: Göttingen
country: Germany
facility: Universitaetsklinikum Göttingen
city: Hagen
country: Germany
facility: St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Halle/Saale
country: Germany
facility: Krankenhaus St. Elisabeth und St. Barbara
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Hamburg
country: Germany
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Nord Heidberg
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus Altona
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Altona
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hannover
country: Germany
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Hannover
country: Germany
facility: Henriettenstiftung Krankenhaus
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Harrislee
country: Germany
facility: Oncology Specialists Clinic
city: Heidelberg
country: Germany
facility: Medizinische Universitaetsklinik und Poliklinik
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Heidenheim
country: Germany
facility: Regional Hospital Heidenheim
city: Heilbronn
country: Germany
facility: Regional Hospital Am Plattenwald - Bad Friedrichhall
city: Herford
country: Germany
facility: Klinikum Herford
city: Herne
country: Germany
facility: Marienhospital at Ruhr University Bochum
city: Herrsching Am Ammersee
country: Germany
facility: Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
city: Hildesheim
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Holzminden
country: Germany
facility: Evang. Hospital
city: Homburg
country: Germany
facility: Medical University Hospital Homburg
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Hoyerswerda
country: Germany
facility: Hospital Complex Hoyerswerda
city: Jena
country: Germany
facility: Gemeinschaftspraxis Innere Medizin
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller Universitaet Jena
city: Kaiserslautern
country: Germany
facility: Municipal Hospital Complex of the University
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Kassel
country: Germany
facility: Red Cross Hospital Kassel
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel
city: Koblenz
country: Germany
facility: Praxis fuer Haematologie und Onkologie
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH
city: Koln-Merheim
country: Germany
facility: Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim
city: Koln
country: Germany
facility: Praxis Fuer Haematologie Internistische Onkologie
city: Koln
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Kornwestheim
country: Germany
facility: Leonardis Clinic
city: Krefeld
country: Germany
facility: Klinikum Krefeld GmbH
city: Kronach
country: Germany
facility: Frankenwald Klinik
city: Lebach
country: Germany
facility: Caritas - Krakenhaus Lebach
city: Leipzig
country: Germany
facility: Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig
city: Leipzig
country: Germany
facility: University Leipzig Clinic of Internal Medicine
city: Leipzig
country: Germany
city: Leipzig
country: Germany
facility: Staedtisches Klinikum "St. Georg" Leipzig
city: Lemgo
country: Germany
facility: Klinikum Lippe - Lemgo
city: Limburg
country: Germany
facility: St. Vincenz Hospital Limburg
city: Lingen
country: Germany
facility: St. Bonifatius Hospital Lingen
city: Lippstadt
country: Germany
facility: Dreifaltigkeits Hospital
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein
city: Ludwigshafen
country: Germany
facility: St. Marien Hospital Ludwighafen
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg - Altstadt
city: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Manheim
country: Germany
facility: German CML Study Group
city: Marburg
country: Germany
city: Marburg
country: Germany
facility: Philipps-Universitaet Marburg Klinikum
city: Mayen
country: Germany
facility: Regional Hospital Mayen
city: Minden
country: Germany
facility: Klinikum Minden
city: Minden
country: Germany
city: Monchenglabach
country: Germany
facility: Ev. Hospital Bethesda
city: Monchengladbach
country: Germany
facility: Hospital Maria-Hilf II
city: Monchenglasbach/Rheydt
country: Germany
city: Mulheim/Ruhr
country: Germany
facility: St. Marien Hospital - Muelheim an der Ruhr
city: Munchberg
country: Germany
facility: Kreiskrankenhaus Muenchberg
city: Munchen
country: Germany
facility: Munich Oncologic Practice at Elisenhof
city: Munchen
country: Germany
facility: Klinikum der Universitaet Muenchen - Innenstadt Campus
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munster
country: Germany
facility: Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
city: Mülheim
country: Germany
facility: Evangelisches Krankenhaus - Mülheim
city: Neumarkt
country: Germany
facility: Regional Hospital Neumarkt
city: Neunkirchen
country: Germany
facility: Staedtisches Klinikum Neunkirchen gGmbH
city: Neuss
country: Germany
facility: Lukaskrankenhaus Neuss
city: Nurnberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Offenburg
country: Germany
facility: Klinikum Offenburg
city: Oldenburg
country: Germany
facility: Hematologische Praxis
city: Oldenburg
country: Germany
facility: Ev. Hospital Oldenburg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Osnabrück
country: Germany
facility: Paracelsus - Klinik Osnabrück
city: Pforzheim
country: Germany
facility: Municipal Hospital Complex
city: Potsdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Radebeul
country: Germany
facility: Kreiskrankenhaus Radebeul
city: Ravensburg
country: Germany
facility: Krankenhaus St. Elisabeth - Ravensburg
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Regensburg
country: Germany
facility: Hematologische Onkologische Praxis
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Rheine
country: Germany
facility: Jakobi Krankenhaus
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock
city: Rostock
country: Germany
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Saarbrucken
country: Germany
facility: Schwerpunktpraxis fuer Haematologie und Onkologie
city: Saarlouis
country: Germany
facility: St. Elizabeth-Klinik Saarlouis
city: Schleswig
country: Germany
facility: Martin - Luther Hospital
city: Schwabisch Hall
country: Germany
facility: Deaconess Hospital
city: Schweinfurt
country: Germany
facility: Leopoldina - Krankenhaus
city: Siegen
country: Germany
facility: Evang. Jung-Stilling Hospital
city: Solingen
country: Germany
facility: St. Lukas - Clinic Solingen
city: Stuttgart
country: Germany
facility: Klinik fuer Onkologie - Katharinenhospital Stuttgart
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart - Buergerhospital
city: Stuttgart
country: Germany
facility: Hospital Bad Cannstatt
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Thuine
country: Germany
facility: St. Elisabeth Hospital Thuine
city: Traunstein
country: Germany
facility: Regional Hospital Traunstein
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Trier
country: Germany
city: Trier
country: Germany
facility: Krankenhaus Der Barmherzigen Brueder
city: Tutzing
country: Germany
facility: Hospital Tutzing
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Unna
country: Germany
facility: Ev. Hospital Unna
city: Vechta
country: Germany
facility: St. Marienhospital - Vechta
city: Villingen-Schwenningen
country: Germany
facility: Klinikum Der Stadt Villingen - Schwenningen
city: Waldbrol
country: Germany
facility: Regional Hospital Waldbrol
city: Wetzlar
country: Germany
facility: Hospital Wetzler
city: Wiesbaden
country: Germany
facility: Deutsche Klinik fuer Diagnostik
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Witten
country: Germany
facility: Ev. Hospital Witten-Herdecke
city: Wuerzburg
country: Germany
facility: University Wurzburg
city: Wuppertal
country: Germany
facility: Kliniken St. Antonius
city: Zwickau
country: Germany
facility: Municipal Hospital Complex Zwickau
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: Zurich
country: Switzerland
facility: City Hospital Triemli
Study officials:
affiliation: Universitaetsklinikum des Saarlandes
name: Michael G.M. Pfreundschuh, MD
role: STUDY_CHAIR
References:
citation: Trumper 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.
citation: Pfreundschuh M, Zwick C, Zeynalova S, Duhrsen U, Pfluger KH, Vrieling T, Mesters R, Mergenthaler HG, Einsele H, Bentz M, Lengfelder E, Trumper L, Rube C, Schmitz N, Loeffler 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: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2008 Mar;19(3):545-52. doi: 10.1093/annonc/mdm514. Epub 2007 Dec 6.