Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Randomised Study Comparing 6 And 8 Cycles Of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine And Prednisone) At 14-Day Intervals (CHOP-14), Both With Or Without The Monoclonal Anti-CD20 Antibody Rituximab In Patients Aged 61 To 80 Years With Aggressive Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00052936
• Other study ID #: CDR0000269015
• Secondary ID: DSHNHL-1999-1AEU
• Status: Completed
• Phase: Phase 3
• Start date: January 2001
• Est. completion date: August 5, 2010

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. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide, doxorubicin, vincristine, and prednisone together with or without rituximab works in treating older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer randomized as of 6/2005).

Description:

OBJECTIVES:

Primary

• Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma.

• Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens.

• Compare the rate of complete remission, rate of primary progression, tumor control, disease-free survival, overall survival, and relapse after radiotherapy in patients treated with these regimens.

• Compare the safety and side effects of these regimens in these patients.

Secondary

• Compare short-term and long-term side effects of these regimens in these patients.

• Compare quality of life of patients treated with these regimens.

• Compare the cost of these regimens in these patients.

• Determine relapse in patients treated with these regimens who received involved-field radiotherapy.

OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label, multicenter study. Patients are stratified according to participating center, value for serum lactic dehydrogenase (no greater than upper limit of normal [ULN] vs greater than ULN), bulky disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0 or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms. Patients with CD20-negative lymphoma are randomized to arms I or II only.

• Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to day 0 before initiating CHOP chemotherapy.

• Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses.

• Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm I for a total of 8 courses.

• Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.

• Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery of bone marrow, and after complete remision of mucositis, patients with sites of initial bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1506
• Est. completion date: August 5, 2010
• Est. primary completion date: August 5, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 61 Years to 80 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) by an excisional biopsy of a lymph node or an extensive biopsy of an extranodal involvement (if there is no lymph node involvement)

• CD20^+ B-cell lymphoma or CD20^- B-cell and T-cell lymphoma allowed

• B-cell NHL including the following:

• Stage III follicular lymphoma

• Stage III follicular lymphoma and diffuse B-cell lymphoma

• Lymphoblastic precursor B-cell lymphoma

• Diffuse large cell B-cell lymphoma

• Centroblastic

• Immunoblastic

• Plasmablastic

• Anaplastic large cell

• T-cell-rich B-cell lymphoma

• Primary effusion lymphoma

• Intravasal B-cell lymphoma

• Primary mediastinal B-cell lymphoma

• Mantle zone lymphoma, blastoid

• Burkitt's lymphoma

• Burkitt-like lymphoma

• Aggressive marginal zone lymphoma (monocytoid)

• T-cell NHL including the following:

• Lymphoblastic precursor T-cell lymphoma

• Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS)

• Lennert's lymphoma

• T-zone lymphoma

• T-cell lymphoma of the angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) type

• Anaplastic large cell lymphoma

• ALK^+

• ALK^-

• Extranodal NK/T-cell lymphoma, nasal type

• Intestinal T/NK-cell lymphoma (with or without enteropathy)

• Hepatosplenic gamma-delta lymphoma

• Subcutaneous panniculitis-like PTCL

• Aggressive T/NK PTCL

• Anaplastic large-cell NHL, NOS

• Bone marrow involvement no more than 25%

• No lymphoma that is clearly restricted to the CNS or originating from the gastrointestinal tract

PATIENT CHARACTERISTICS:

Age

• 61 to 80

Performance status

• ECOG 0-2 OR

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3

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

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)

• No active hepatitis infection

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• No Canadian Cardiovascular Society class III or IV angina pectoris

• No New York Heart Association class III or IV cardiac failure

• Ejection fraction at least 50%

• Fractional shortenings at least 25% by echocardiography or nuclear medicine examination

Pulmonary

• FEV1 at least 50%

• Diffusion capacity at least 50%

Other

• No uncontrolled diabetes mellitus

• No known hypersensitivity to any study medications

• No other concurrent malignancy

• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• Must not have already initiated lymphoma therapy (except for the prephase treatment specified for this study)

• No other concurrent lymphoma therapy

• No concurrent participation in another treatment study

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim

• rituximab

Drug:
• CHOP regimen

• cyclophosphamide

• doxorubicin hydrochloride

• prednisone

• vincristine sulfate

Radiation:
• radiation therapy
36Gy on BULK and extranodal involvement

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	Regional Hospital Bad Hersfeld	Bad Hersfeld
Germany	Humaine - Clinic	Bad Saarow
Germany	Krankenhaus Hohe Warte Mediziniche Klinik	Bayreuth
Germany	Haematologisch-Onkologische Schwerpunktpraxis	Berlin
Germany	Robert Roessle Comprehensive Cancer Center - Charite Campus Buch	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	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Praxis Fuer Haematologie Internistische Onkologie	Cologne
Germany	Lung Clinic Cologne-Merheim	Cologne-Merheim
Germany	Carl - Thiem - Klinkum Cottbus	Cottbus
Germany	Klinikum Darmstadt	Darmstadt
Germany	Saint Johannes Hospital Dortmund	Dortmund
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	St. Johannes Hospital - Medical Klinik II	Duisburg
Germany	Franz Hospital Dulmen	Dulmen
Germany	Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth	Dusseldorf
Germany	Hans - Susemihl - Krankenhaus	Emden
Germany	Klinikum Erfurt	Erfurt
Germany	St. Antonius Hospital	Eschweiler
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 Gieben	Gießen
Germany	Universitaetsklinikum Goettingen	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	University Medical Center 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 Friedrichshall	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	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	Leonardis Clinic	Kornwestheim
Germany	Klinikum Krefeld GmbH	Krefeld
Germany	Frankenwald Klinik	Kronach
Germany	Caritas - Krakenhaus Lebach	Lebach
Germany	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	Municipal Complex of Ludwigshafen	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	III Medizinische Klinik Mannheim	Mannheim
Germany	Universitaetsklinikum Giessen und Marburg GmbH - Marburg	Marburg
Germany	Regional Hospital Mayen	Mayen
Germany	Klinikum Minden	Minden
Germany	Ev. Hospital Bethesda	Monchengladbach
Germany	Hospital Maria-Hilf II	Monchengladbach
Germany	Evangelisches Krankenhaus - Mulheim	Mulheim/Ruhr
Germany	St. Marien Hospital - Muelheim an der Ruhr	Mulheim/Ruhr
Germany	Kreiskrankenhaus Muenchberg	Munchberg
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum der Universitaet Muenchen - Innenstadt Campus	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
Germany	Munich Oncologic Practice at Elisenhof	Munich
Germany	Municipal Hospital Munich	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	Nuremberg
Germany	Klinikum Offenburg	Offenburg
Germany	Ev. Hospital Oldenburg	Oldenburg
Germany	Hematologische Praxis	Oldenburg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Paracelsus - Klinik Osnabrueck	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	Saarbruecken
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 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	Municipal Hospital Complex	Villingen-Schwenningen
Germany	Regional Hospital Waldbrol	Waldbrol
Germany	Evangelisches Krankenhaus Essen Werden	Werden
Germany	Hospital Wetzler	Wetzlar
Germany	Deutsche Klinik fuer Diagnostik	Wiesbaden
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Ev. Hospital Witten-Herdecke	Witten
Germany	Kliniken St. Antonius	Wuppertal
Germany	University Wurzburg	Wurzburg
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 (1)

Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to treatment failure at 3 years within the study and then periodically after study completion		3 years within the study and then periodically after study completion
Secondary	Complete response rate at 3 years within the study and then periodically after study completion		3 years within the study and then periodically after
Secondary	Progression rate		3 years within the study and then periodically after
Secondary	Survival		3 years within the study and then periodically after
Secondary	Tumor control		3 years within the study and then periodically after
Secondary	Disease-free survival		3 years within the study and then periodically after

External Links

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