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: Randomized phase III trial to compare the effectiveness of cyclophosphamide, doxorubicin, vincristine, and prednisone with or without rituximab in treating older patients who have aggressive non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult T-cell leukemia and lymphoma anaplastic large cell lymphoma angioimmunoblastic T-cell lymphoma Non-Hodgkin's Lymphoma	Drug: cyclophosphamide  Drug: doxorubicin  Drug: filgrastim  Drug: prednisone  Drug: rituximab  Drug: vincristine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

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

OUTLINE: This is a randomized, 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: 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: 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: 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 880 patients (220 per treatment arm) will be accrued for this study within 5 years.

Ages Eligible for Study:  61 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

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

Germany
      Leipzig,  D-04103,  Germany; Recruiting
      Allgemeines Krankenhaus Altona, Hamburg,  22763,  Germany; Recruiting
      Allgemeines Krankenhaus Hagen, Hagen,  58095,  Germany; Recruiting
      Minden,  D-32427,  Germany; Recruiting
      Augsburg,  86150,  Germany; Recruiting
      Buergerhospital Stuttgart, Stuttgart,  70191,  Germany; Recruiting
      Caritas - Krakenhaus Lebach, Lebach,  66822,  Germany; Recruiting
      Caritasklinik St. Theresia, Saarbrucken,  66113,  Germany; Recruiting
      Carl - Thiem - Klinkum Cottbus, Cottbus,  03048,  Germany; Recruiting
      Centre for Internal Medicine Gieben, Gieben,  35392,  Germany; Recruiting
      Deaconess Hospital, Schwabisch Hall,  74523,  Germany; Recruiting
      Deutsche Klinik fuer Diagnostik, Wiesbaden,  65191,  Germany; Recruiting
      Diakonissen-Krankenhaus Stuttgart, Stuttgart,  70176,  Germany; Recruiting
      Dr. Horst-Schmidt-Kliniken, Wiesbaden,  65199,  Germany; Recruiting
      Dreifaltigkeits Hospital, Lippstadt,  59555,  Germany; Recruiting
      Ernst-Moritz-Arndt University, Greifswald,  17489,  Germany; Recruiting
      Ev. Diakome Krankenhaus gGmBH, Bremen,  28239,  Germany; Recruiting
      Ev. Hospital Bethesda, Monchengladbach,  41061,  Germany; Recruiting
      Ev. Hospital Oldenburg, Oldenburg,  26122,  Germany; Recruiting
      Ev. Hospital Unna, Unna,  59403,  Germany; Recruiting
      Ev. Hospital Witten-Herdecke, WITTEN,  58455,  Germany; Recruiting
      Ev. Hospital, Mulheim/Ruhr,  45466,  Germany; Recruiting
      Evang. Deaconess Hospital Freiburg, Freiburg,  79110,  Germany; Recruiting
      Evang. Hospital, Holzminden,  37603,  Germany; Recruiting
      Evang. Jung-Stilling Hospital, Siegen,  57074,  Germany; Recruiting
      Evang. Stift St. Martin gGmbH Koblenz, Koblenz,  56068,  Germany; Recruiting
      Evangelische Krankenhaus Hamm, Hamm,  59063,  Germany; Recruiting
      Evangelisches Krankenhaus Essen Werden, Essen-Werden,  45239,  Germany; Recruiting
      Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth, Dusseldorf,  40489,  Germany; Recruiting
      Frankenwald Klinik, Kronach,  96317,  Germany; Recruiting
      Franz Hospital Dulmen, Dulmen,  48249,  Germany; Recruiting
      Hannover,  30159,  Germany; Recruiting
      Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie, Ansbach,  91522,  Germany; Recruiting
      Gemeinschaftspraxis Innere Medizin, Jena,  D-07743,  Germany; Recruiting
      General Hospital, CELLE,  29223,  Germany; Recruiting
      Monchenglasbach/Rheydt,  D-41239,  Germany; Recruiting
      Trier,  D-54290,  Germany; Recruiting
      Haematologisch Onkologische Praxis, Aachen,  52070,  Germany; Recruiting
      Haematologische Praxis, Augsburg,  86150,  Germany; Recruiting
      Haematologisch-Onkologische Praxis Altona, Hamburg,  D-22767,  Germany; Recruiting
      Haematologisch-Onkologische Schwerpunktpraxis, Berlin,  13357,  Germany; Recruiting
      Hans - Susemihl - Krankenhaus, Emden,  26721,  Germany; Recruiting
      Hematologische Onkologische Praxis, Regensburg,  93047,  Germany; Recruiting
      Hematologische Praxis, Oldenburg,  26121,  Germany; Recruiting
      Hospital Altstadt Magdeburg, Magdeburg,  39104,  Germany; Recruiting
      Hospital Bad Cannstatt, Stuttgart,  70374,  Germany; Recruiting
      Hospital Complex Bernburg, Bernburg,  06406,  Germany; Recruiting
      Hospital Complex Hoyerswerda, Hoyerswerda,  02977,  Germany; Recruiting
      Hospital Complex North, Heidberg, Hamburg,  22413,  Germany; Recruiting
      Hospital Complex of the University Regensburg, Regensburg,  93042,  Germany; Recruiting
      Hospital Kuchwald Chemnitz, Chemnitz,  09113,  Germany; Recruiting
      Hospital Maria-Hilf II, Monchengladbach,  41063,  Germany; Recruiting
      Hospital Neunkirchen gGmbH, Neunkirchen,  66538,  Germany; Recruiting
      Hospital Tutzing, Tutzing,  82327,  Germany; Recruiting
      Hospital Wetzler, Wetzlar,  35578,  Germany; Recruiting
      Humaine - Clinic, Bad Saarow,  15523,  Germany; Recruiting
      II. Medizinische Klinik, Aschaffenburg,  63739,  Germany; Recruiting
      III Medizinische Klinik Mannheim, Mannheim,  D-68305,  Germany; Recruiting
      Jakobi Krankenhaus, Rheine,  48431,  Germany; Recruiting
      Johannes Gutenberg University, Mainz,  55131,  Germany; Recruiting
      Klinik fuer Onkologie - Katharinenhospital Stuttgart, Stuttgart,  70174,  Germany; Recruiting
      Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock, Rostock,  18057,  Germany; Recruiting
      Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock, Rostock,  18059,  Germany; Recruiting
      Kliniken St. Antonius, Wuppertal,  42283,  Germany; Recruiting
      Klinikum Darmstadt, Darmstadt,  64283,  Germany; Recruiting
      Klinikum der Friedrich-Schiller Universitaet Jena, Jena,  07747,  Germany; Recruiting
      Klinikum Erfurt, Erfurt,  99089,  Germany; Recruiting
      Klinikum Ernst Von Bergmann, Potsdam,  14467,  Germany; Recruiting
      Klinikum Frankfurt, Frankfurt/Oder,  15236,  Germany; Recruiting
      Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen, Munich,  81377,  Germany; Recruiting
      Klinikum Krefeld GmbH, Krefeld,  47805,  Germany; Recruiting
      Klinikum Krollwitz, Halle,  06120,  Germany; Recruiting
      Klinikum Lippe - Lemgo, LEMGO,  32657,  Germany; Recruiting
      Klinikum Ludwigsburg, Ludwigsburg,  71640,  Germany; Recruiting
      Klinikum Minden, Minden,  32423,  Germany; Recruiting
      Klinikum Nuernberg - Klinikum Nord, Nuremberg,  90340,  Germany; Recruiting
      Klinikum Offenburg, Offenburg,  77654,  Germany; Recruiting
      Klinikum Oldenburg, Oldenburg,  26133,  Germany; Recruiting
      Klinikum St. Marien, Amberg,  92224,  Germany; Recruiting
      Knappschaft Krankenhaus, Bochum,  44892,  Germany; Recruiting
      Krankenhaus Bietigheim, Bietigheim,  74321,  Germany; Recruiting
      Krankenhaus D Barmherzigen Brueder, Regensburg,  93049,  Germany; Recruiting
      Krankenhaus der Barmherzigen Brueder, Trier,  54292,  Germany; Recruiting
      Krankenhaus Hohe Warte Mediziniche Klinik, Bayreuth,  95445,  Germany; Recruiting
      Krankenhaus Nordwest, Frankfurt,  60488,  Germany; Recruiting
      Krankenhaus Siloah - Medizinische Klinik II, Hannover,  30449,  Germany; Recruiting
      Kreiskrankenhaus Aurich, Aurich,  26603,  Germany; Recruiting
      Kreiskrankenhaus Radebeul, Radebeul,  01445,  Germany; Recruiting
      Kreiskrankenhaus, Herford,  32049,  Germany; Recruiting
      Rostock,  D-18257,  Germany; Recruiting
      Leonardis Clinic, Kornwestheim,  70806,  Germany; Recruiting
      Leopoldina - Krankenhaus, Schweinfurt,  97422,  Germany; Recruiting
      Lukaskrankenhaus Neuss, Neus,  41464,  Germany; Recruiting
      Lung Clinic Cologne-Merheim, Cologne-Merheim,  51109,  Germany; Recruiting
      Cologne-Kalk,  D-51105,  Germany; Recruiting
      Marienhospital / Ruhr University Bochum, Herne,  44625,  Germany; Recruiting
      Marienhospital, Vechta,  49377,  Germany; Recruiting
      Martin - Luther Hospital, Schleswig,  24837,  Germany; Recruiting
      Medical University Hospital Homburg, Homburg,  66421,  Germany; Recruiting
      Medical University of Lubeck, Lubeck,  23538,  Germany; Recruiting
      Medizinische Hochschule Hannover, Hannover,  30625,  Germany; Recruiting
      Medizinische Kl. Klinikum Innenstadt Universitaet Muenchen, Munich,  80336,  Germany; Recruiting
      Medizinische Klinik Am Lukas - Krankenhaus, Bunde,  32257,  Germany; Recruiting
      Medizinische Klinik I, Dresden,  01307,  Germany; Recruiting
      Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster, Munster,  48129,  Germany; Recruiting
      Medizinische Poliklinik, Bonn,  53111,  Germany; Recruiting
      Medizinische Universitaetsklinik I, Cologne,  50924,  Germany; Recruiting
      Medizinische Universitaetsklinik und Poliklinik, Heidelberg,  69115,  Germany; Recruiting
      Medizinischen Klinik Dr. R. Schindlbeck, Herrsching,  82211,  Germany; Recruiting
      Munich Oncologic Practice at Elisenhof, Munich,  80335,  Germany; Recruiting
      Municipal Complex of Ludwigshafen, Ludwigshafen,  67063,  Germany; Recruiting
      Municipal Hospital Complex of the University, Kaiserslautern,  67655,  Germany; Recruiting
      Municipal Hospital Complex Zwickau, Zwickau,  08060,  Germany; Recruiting
      Municipal Hospital Complex, Villingen-Schwenningen,  78045,  Germany; Recruiting
      Municipal Hospital Complex, Pforzheim,  75175,  Germany; Recruiting
      Municipal Hospital Complex, Fulda,  36043,  Germany; Recruiting
      Municipal Hospital Munich Schwarbing, Munich,  80804,  Germany; Recruiting
      Municipal Hospital Munich, Munich,  81737,  Germany; Recruiting
      Mutterhaus der Borromaerinnen, Trier,  54290,  Germany; Recruiting
      Neurologische Klinik - Henriettenstiftung, Hannover,  30559,  Germany; Recruiting
      Oncological Specialist Practice, Harrislee,  24955,  Germany; Recruiting
      Oncological Specialist Practice, Hildesheim,  31134,  Germany; Recruiting
      Paracelsus - Clinic Osnabruck, Osnabruck,  49076,  Germany; Recruiting
      Philipps-Universitaet Marburg Klinikum, Marburg,  35043,  Germany; Recruiting
      Praxis Fuer Haematologie Internistische Onkologie, Koeln,  D-50677,  Germany; Recruiting
      Praxis fuer Haematologie und Onkologie, Koblenz,  D-56068,  Germany; Recruiting
      Red Cross Hospital Kassel, Kassel,  34121,  Germany; Recruiting
      Regional Hospital Am Plattenwald, Bad Friedrichshall,  74172,  Germany; Recruiting
      Regional Hospital Bad Hersfeld, Bad Hersfeld,  36251,  Germany; Recruiting
      Regional Hospital Heidenheim, Heidenheim,  89522,  Germany; Recruiting
      Regional Hospital Mayen, Mayen,  56727,  Germany; Recruiting
      Regional Hospital Munchberg, Munchberg,  95213,  Germany; Recruiting
      Regional Hospital Neumarkt, Neumarkt,  92318,  Germany; Recruiting
      Regional Hospital Traunstein, Traunstein,  83278,  Germany; Recruiting
      Regional Hospital Waldbrol, Waldbrol,  51545,  Germany; Recruiting
      Rheinische Friedrich-Wilhelms-Universitat, Bonn,  D-53113,  Germany; Recruiting
      Robert - Koch Hospital, Gehrden,  30989,  Germany; Recruiting
      Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch, Berlin,  13125,  Germany; Recruiting
      Robert-Bosch-Krankenhaus, Stuttgart,  70376,  Germany; Recruiting
      Saint Agnes Hospital, Bocholt,  46397,  Germany; Recruiting
      Saint Elisabeth / Saint Barbara Hospital, Halle/Saale,  06110,  Germany; Recruiting
      Saint Johannes Hospital Dortmund, Dortmund,  44137,  Germany; Recruiting
      Saint Josef Hospital, Bochum,  44791,  Germany; Recruiting
      Schwerpunktpraxis Fuer Haematologie Und Onkologie, Saarbruecke,  N-66113,  Germany; Recruiting
      Specialist Practice for Oncology, Aschaffenburg,  63739,  Germany; Recruiting
      St. Antonius Hospital, Eschweiler,  52249,  Germany; Recruiting
      St. Bonifatius Hospital Lingen, Lingen,  49808,  Germany; Recruiting
      St. Elisabeth Hospital Ravensburg, Ravensburg,  88212,  Germany; Recruiting
      St. Elisabeth Hospital Thuine, Thuine,  49832,  Germany; Recruiting
      St. Elisabeth Hospital, Saarlouis,  66713,  Germany; Recruiting
      St. Johannes Hospital - Medical Klinik II, Duisburg,  47166,  Germany; Recruiting
      St. Lukas - Clinic Solingen, Solingen,  42697,  Germany; Recruiting
      St. Marien Hospital - Muelheim an der Ruhr, Mulheim/Ruhr,  45468,  Germany; Recruiting
      St. Marien Hospital at Katholisches Krankenhaus hagen gem. GmbH, Hagen,  58095,  Germany; Recruiting
      St. Marien Hospital Ludwighafen, Ludwigshafen,  67067,  Germany; Recruiting
      St. Vincenz Hospital Limburg, Limburg,  65549,  Germany; Recruiting
      Stadisches Krankenhaus Martha Maria Halle-Dolau, Halle,  06120,  Germany; Recruiting
      Stadt Krankenhaus Gutersloh, Gutersloh,  33332,  Germany; Recruiting
      Staedt Klinikum Karlsruhe GGMBH, Karlsruhe,  76133,  Germany; Recruiting
      Staedtische Krankenhaus Kiel, Kiel,  23116,  Germany; Recruiting
      Staedtisches Klinikum "St. Georg" Leipzig, Leipzig,  04129,  Germany; Recruiting
      Thoraxklinik Heidelberg, Heidelberg,  69126,  Germany; Recruiting
      Universitaetsklinikum Essen, ESSEN,  45147,  Germany; Recruiting
      Universitaetsklinikum Goettingen, Gottingen,  37075,  Germany; Recruiting
      Universitaetsklinikum Ulm, Ulm,  89081,  Germany; Recruiting
      Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg, Magdeburg,  39120,  Germany; Recruiting
      Universitaets-Krankenhaus Eppendorf, Hamburg,  20251,  Germany; Recruiting
      University Leipzig Clinic of Internal Medicine, Leipzig,  04103,  Germany; Recruiting
      University Wurzburg, Wurzburg,  97070,  Germany; Recruiting
      Marburg,  D-35037,  Germany; Recruiting
      Hamburg,  20095,  Germany; Recruiting
      Zentralklinikum Augsburg, Augsburg,  86156,  Germany; Recruiting
Switzerland
      City Hospital Triemli, Zurich,  8063,  Switzerland; Recruiting
      UniversitaetsSpital, Zurich,  8091,  Switzerland; Recruiting

Study chairs or principal investigators

Michael G.M. Pfreundschuh, MD,  Study Chair,  Universitatsklinik - Saarland   

Study ID Numbers:  CDR0000269015; DSHNHL-1999-1A; EU-20243; NCT00052936
Record last reviewed:  December 2002
Last Updated:  January 6, 2005
Record first received:  January 24, 2003
ClinicalTrials.gov Identifier:  NCT00052936
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08