Rituximab and Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2009 by National Cancer Institute (NCI)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00278421
First received: January 16, 2006
Last updated: April 16, 2010
Last verified: July 2009
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which schedule of rituximab and combination chemotherapy is more effective in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study Comparing 4 and 6 Cycles of Chemotherapy With CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) at 21-day Intervals, Both With 6 Cycles of Immunotherapy With the Monoclonal Anti-CD20-Positive B-Cell Lymphoma Aged 18-60 Years Having no Risk Factor (Age-Adjusted IPI=0) and No Large Tumor Mass (Diameter <7,5cm) [FLYER 6-6-6-4 Study]

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to treatment failure (TTF) measured from day 1 of course 1 of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) therapy up to 3 years on study with life-long follow-up [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response (CR) rate duration until first relapse [ Designated as safety issue: No ]
  • Progression rate during treatment [ Designated as safety issue: No ]
  • Survival [ Designated as safety issue: No ]
  • Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored) [ Designated as safety issue: No ]
  • Disease-free survival measured from day 1 of course 1 of CHOP therapy [ Designated as safety issue: No ]
  • Safety (adverse events, serious adverse events) assessed at 3 months after treatment [ Designated as safety issue: Yes ]

Estimated Enrollment: 622
Study Start Date: November 2005
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Compare the efficacy of 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in patients with previously untreated, low-risk, aggressive B-cell non-Hodgkin's lymphoma.
  • Compare acute and chronic side effects in patients treated with these regimens.
  • Compare time to treatment failure in patients treated with these regimens.

Secondary

  • Compare the time to progression in patients treated with these regimens.
  • Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.
  • Compare the complete response rate in patients treated with these regimens.
  • Compare the tumor control in patients treated with these regimens.
  • Compare the safety of these regimens in these patients.
  • Compare the pharmacoeconomics of these regimens.
  • Compare patient adherence to these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

All patients are given the option of receiving a 1-week course of pretreatment therapy comprising vincristine IV once on day -6 and oral prednisone once daily on days -6 to 0.

  • Arm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
  • Arm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.

All patients undergo final restaging after 6 courses of rituximab. Patients with disease progression, stable disease, or partial response proceed to salvage therapy off study.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 622 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma, including the following subtypes:

    • Grade 3 follicular lymphoma
    • Diffuse B-cell lymphoma, including diffuse large cell lymphoma with any of the following variants:

      • Centroblastic
      • Immunoblastic
      • Plasmablastic
      • Anaplastic large cell
      • T-cell-rich B-cell lymphoma
    • Primary effusion lymphoma
    • Intravascular B-cell lymphoma
    • Primary mediastinal B-cell lymphoma
    • Burkitt's or Burkitt-like lymphoma
    • Mantle cell lymphoma (blastoid)
    • Aggressive marginal zone lymphoma (monocytoid)
  • Previously untreated disease
  • CD20-positive disease
  • International Prognostic Index (IPI) score 0
  • No bulky disease

    • Largest single or conglomerate tumor < 7.5 cm in diameter
  • No mucosa-associated lymphoid tissue (MALT) lymphoma
  • No CNS involvement of lymphoma (intracerebral, meningeal, or intraspinal)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 2,500/mm^3
  • Lactate dehydrogenase normal
  • Not pregnant or lactating
  • Fertile patients must use effective contraception during and for 1 year after study participation
  • Negative pregnancy test
  • No known hypersensitivity to the study medications
  • No known HIV-positivity
  • No active hepatitis infection
  • No impaired left ventricular function
  • No severe cardiac arrhythmias
  • No other impaired organ function
  • No other serious disorder
  • No other malignancy within the past 5 years except carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy
  • No prior immunosuppressive treatment with cytostatics
  • No planned radiotherapy to extranodal involvement
  • No concurrent participation in other treatment studies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00278421

  Hide Study Locations
Locations
Germany
Haematologisch Onkologische Praxis Recruiting
Aachen, Germany, 52070
Contact: D. Tummes, MD    49-241-990-0550    tummes@onkologie-aachen.de   
Klinikum Augsburg Recruiting
Augsburg, Germany, DOH-86156
Contact: Gunter Schlimok, MD    49-821-400-2353    schlimok@klinikum-augsburg.de   
Klinikum Bayreuth Recruiting
Bayreuth, Germany, D-95445
Contact: Contact Person    49-921-400-00      
Haematologisch-Onkologische Schwerpunktpraxis - Weilheim Recruiting
Berlin, Germany, 13357
Contact: Ilona Blau, MD    49-30-461-4857      
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin Recruiting
Berlin, Germany, D-12200
Contact: Eckhard Thiel, MD    49-30-8445-2337    haema.cbf@charite.de   
Franziskus Hospital Recruiting
Bielefeld, Germany, D-33615
Contact: H.J. Weh, MD    49-521-5897-1200      
Augusta-Kranken-Anstalt gGmbH Recruiting
Bochum, Germany, D-44791
Contact: D. Behringer, MD    49-234-517-2430    behringer@augusta-bochum.de   
Staedtisches Klinikum Braunschweig Recruiting
Braunschweig, Germany, G-38114
Contact: Contact Person    49-531-595-3224      
DIAKO Ev. Diakonie Krankenhaus gGmbH Recruiting
Bremen, Germany, D-28239
Contact: Karl-Heinz Pflueger, MD    49-421-6102-1481    pfluegerkh@diako-bremen.de   
Hospital Kuchwald Chemnitz Recruiting
Chemnitz, Germany, D-09113
Contact: Contact Person    49-371-333-42700      
Praxis Fuer Haematologie Internistische Onkologie Recruiting
Cologne, Germany, D-50677
Contact: C. Gabor, MD    49-221-931-8220      
Medizinische Universitaetsklinik I at the University of Cologne Recruiting
Cologne, Germany, D-50924
Contact: Michael Hallek, MD    49-221-478-4400      
Carl - Thiem - Klinkum Cottbus Recruiting
Cottbus, Germany, D-03048
Contact: H. B. Steinhauer, MD    49-355-462-223      
Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke Recruiting
Damme, Germany, D-49401
Contact: Rheinhold Siegmund, MD    49-554-91-90-90-80      
Klinikum Dortmund Recruiting
Dortmund, Germany, D-44137
Contact: Michael Heike, MD    49-231-9532-1770    michael.heike@klinikumdo.de   
Hans - Susemihl - Krankenhaus Recruiting
Emden, Germany, 26721
Contact: H. Becker, MD    49-4921-981-295    h.becker@hsk-emden.de   
St. Antonius Hospital Recruiting
Eschweiler, Germany, DOH-52249
Contact: Roland Fuchs, MD    49-240-376-1280    info@onkologie-eschweiler.de   
Universitaetsklinikum Essen Recruiting
Essen, Germany, D-45122
Contact: Ulrich Duehrsen, MD    49-41-945-000    ulrich.duehrsen@uk-essen.de   
Klinikum Frankfurt (Oder) GmbH Recruiting
Frankfurt (Oder), Germany, D-15236
Contact: Michael G. Kiehl, MD, PhD    49-335-548-4601    m.kiehl.km@klinikumffo.de   
Universitaetsklinikum Freiburg Recruiting
Freiburg, Germany, D-79106
Contact: Roland H. Mertelsmann, MD, PhD    49-761-270-7367    mertelsmann@mmll.ukl.uni-freiburg.de   
Klinikum Fulda Recruiting
Fulda, Germany, D-36013
Contact: Heinz-Gert Hoeffkes, MD    49-661-84-54-81    hoeffkes.tumorklinik@klinikum-fulda.de   
Saint Josef Hospital Recruiting
Gelsenkirchen, Germany, D-45899
Contact: Contact Person    49-209-504-5300      
Universitaetsklinikum Goettingen Recruiting
Goettingen, Germany, D-37075
Contact: L. Trumper    49-551-396-810      
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet Recruiting
Greifswald, Germany, D-17475
Contact: Gottfried Doelken, MD    49-3834-866-698    doelken@uni-greifswald.de   
Kreiskrankenhaus Gummersbach GMBH Recruiting
Gummersbach, Germany, D-51643
Contact: Sieber, MD    49-2261-171-350      
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH Recruiting
Hagen, Germany, D-58095
Contact: Hartmut Eimermacher, MD    49-2331-129-250      
St. Sixtus Hospital Recruiting
Haltern, Germany, D-45721
Contact: A. Bracht, MD    49-2364-1040      
Haematologisch-Onkologische Praxis Altona Recruiting
Hamburg, Germany, D-22767
Contact: Wiebke Hollburg, MD    49-40-3802-1280      
University Medical Center Hamburg - Eppendorf Recruiting
Hamburg, Germany, D-20246
Contact: Carsten Bokemeyer, MD    49-40-428-030    c.bokemeyer@uke.uni-hamburg.de   
Asklepios Klinik St. Georg Recruiting
Hamburg, Germany, D-20099
Contact: Contact Person    49-40-1818-8511      
Evangelische Krankenhaus Hamm Recruiting
Hamm, Germany, DOH-59063
Contact: Leopold Balleisen, MD    49-2381-589-1275    LBalleisen@evkhamm.de   
St. Marien-Hospital Hamm - Klinik Knappenstrasse Recruiting
Hamm, Germany, D-59071
Contact: Heinz A. Duerk, MD, PhD    49-2381-18-22-51    heinz.duerk@marienhospital-hamm.de   
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, D-30625
Contact: Arnold Ganser, PhD, MD    49-511-532-3020    ganser.arnold@mh-hannover.de   
Ruprecht - Karls - Universitaet Heidelberg Recruiting
Heidelberg, Germany, 69115
Contact: Anthony D. Ho, MD, PhD    49-6221-56-8001    anthony_ho@med.uni-heidelberg.de   
St. Bernward Krankenhaus Recruiting
Hildesheim, Germany, D-31134
Contact: Ulrich Kaiser, MD    49-5-121-90-12-73    u.kaiser@bernward-khs.de   
Universitaetsklinikum des Saarlandes Recruiting
Homburg, Germany, D-66424
Contact: Michael G.M. Pfreundschuh, MD    49-6841-162-3084    michael.pfreundschuh@uniklinik-saarland.de   
Clinic for Bone Marrow Transplantation and Hematology and Oncology Recruiting
Idar-Oberstein, Germany, D-55743
Contact: Axel A. Fauser, MD, PhD    49-6781-66-1590      
Staedtisches Klinikum Karlsruhe gGmbH Recruiting
Karlsruhe, Germany, 76133
Contact: Martin Bentz    49-721-974-3001      
St. Vincentius - Kliniken Recruiting
Karlsruhe, Germany, D-76137
Contact: J. Mezger, MD    49-721-8108-3014      
Klinikum Kempten Oberallgaeu Recruiting
Kempten, Germany, D-87439
Contact: Otto Pruemmer, MD    49-549-19-09-08-0    otto.pruemmer@klinikum-kempten.de   
University Hospital Schleswig-Holstein - Kiel Campus Recruiting
Kiel, Germany, D-24116
Contact: Michael Kneba    49-431-1697-1201      
Caritas - Krakenhaus Lebach Recruiting
Lebach, Germany, 66822
Contact: Stephan Kremers, MD    49-68-881-5010      
Klinikum Lippe - Lemgo Recruiting
Lemgo, Germany, D-32657
Contact: Frank Hartmann, MD    49-5261-264-123    frank.hartmann@klinikum-lippe.de   
St. Vincenz Hospital Limburg Recruiting
Limburg, Germany, D-65549
Contact: K. P. Schalk, MD    49-6431-292-4330      
Klinikum der Stadt Ludwigshafen am Rhein Recruiting
Ludwigshafen am Rhein, Germany, D-67063
Contact: Martin Hoffmann, MD    49-621-503-3942    hoffmanm@klilu.de   
Kreiskrankenhaus Luedenscheid Recruiting
Luedenscheid, Germany, 58515
Contact: Gerhard Heil, MD    49-235-1460      
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg Recruiting
Magdeburg, Germany, D-39120
Contact: Martin Mohren, MD    49-391-671-3266    martin.mohren@medizin.uni-magdeburg.de   
III Medizinische Klinik Mannheim Recruiting
Mannheim, Germany, D-68305
Contact: Ruediger Hehlmann, MD    49-621-383-4115    Ruediger.Hehlmann@med3.ma.uni-heidelberg.de   
Universitaetsklinikum Giessen und Marburg GmbH - Marburg Recruiting
Marburg, Germany, D-35033
Contact: Andreas Neubauer, MD    49-6421-28-66-273    neubauer@mailer.uni-marburg.de   
Krankenhaus Ludmillenstift Recruiting
Meppen, Germany, 49716
Contact: Ulrich Ohl, MD    49-5931-152-1400      
Krankenhaus Maria Hilf GmbH Recruiting
Moenchengladbach, Germany, D-41063
Contact: Ullrich Graeven, MD, PhD    49-2161-892-2212    inneren@mariahilf.de   
Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster Recruiting
Muenster, Germany, D-48149
Contact: Contact Person    49-251-837-586      
Haematologisch - Onkologische Gemeinschaftspraxis - Muenster Recruiting
Muenster, Germany, D-48149
Contact: Christian Lerchenmueller, MD    49-251-620-080      
Klinikum Rechts Der Isar - Technische Universitaet Muenchen Recruiting
Munich, Germany, D-81675
Contact: Ulrich Keller, MD    49-89-4140-7435    ulrich.keller@lrz.tum.de   
Klinikum der Universitaet Muenchen - Grosshadern Campus Recruiting
Munich, Germany, D-81377
Contact: Wolfgang Hiddemann, MD, PhD    49-89-7095-2551      
Klinikum Schwaebisch Gmuend Stauferklinik Recruiting
Mutlangen, Germany, D-73557
Contact: Holger Hebart, MD    49-7171-701-1302    holger.hebart@klinikum-sgd.de   
Onkologische Schwerwpunktpraxis Dr. Ladda Recruiting
Neumarkt, Germany, D-92318
Contact: Ekkehart Ladda, MD    49-91-8146-4526    ekkehart.ladda@gmx.de   
Lukaskrankenhaus Neuss Recruiting
Neuss, Germany, D-41464
Contact: Contact Person    49-2131-888-2701      
Schlossbergkliniken Oberstaufen Recruiting
Oberstaufen, Germany, D-87534
Contact: Contact Person    49-8386-7010      
Klinikum Oldenburg Recruiting
Oldenburg, Germany, D-26133
Contact: Claus-Henning Koehne, MD    49-441-403-2648    onkologie@klinikum-oldenburg.de   
Recruiting
Pforzheim, Germany, 75179
Contact: Yves Dencausse, MD    49-7231-280-3780      
Klinikum Ernst Von Bergmann Recruiting
Potsdam, Germany, D-14467
Contact: Georg Maschmeyer, MD    49-331-241-6002    gmaschmeyer@klinikumevb.de   
Prosper-Hospital Recklinghausen Recruiting
Recklinghausen, Germany, DOH-45659
Contact: Thomas Hoehler, MD    49-2361-54-26-51      
Recruiting
Rostock, Germany, D-18257
Contact: Volker Lakner, MD    49-381-493-4276      
St. Marien - Krankenhaus Siegen GMBH Recruiting
Siegen, Germany, D-57072
Contact: Winfried Gassmann, MD    49-271-231-1310      
Diakonie Klinikum Stuttgart Recruiting
Stuttgart, Germany, D-70176
Contact: Contact Person    49-711-991-3500      
Krankenanstalt Mutterhaus der Borromaerinnen Recruiting
Trier, Germany, D-54219
Contact: Michael Clemens, MD    49-651-947-2376    clemens@uni-trier.de   
Southwest German Cancer Center at Eberhard-Karls-University Recruiting
Tuebingen, Germany, D-72076
Contact: Lothar Kanz, MD    49-7071-298-2726    lothar.kanz@med.uni-tuebingen.de   
Universitaetsklinikum Tuebingen Recruiting
Tuebingen, Germany, D-72076
Contact: Contact Person    49-7071-298-2087      
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm Recruiting
Ulm, Germany, D-89081
Contact: Hartmut Doehner, MD    49-731-3002-4401    hartmut.doehner@uniklinik-ulm.de   
St. Marienhospital - Vechta Recruiting
Vechta, Germany, D-49377
Contact: J. Diers, MD    49-4441-99-1201      
Onkologische Schwerpunktpraxis Recruiting
Wendlingen, Germany, 73240
Contact: Robert Eckert, MD    49-70-242-331      
Dr. Horst-Schmidt-Kliniken Recruiting
Wiesbaden, Germany, D-65199
Contact: Norbert Frickhofen, MD    49-611-433-018    norbert.frickhofen@hsk-wiesbaden.de   
Helios Kliniken Wuppertal University Hospital Recruiting
Wuppertal, Germany, D-42283
Contact: Contact Person    49-202-896-2820      
Israel
Rabin Medical Center - Beilinson Campus Recruiting
Petah-Tikva, Israel, 49100
Contact: Contact Person    972-3-937-7377      
Italy
Ospedale Civile - Piacenza Recruiting
Piacenza, Italy, 29100
Contact: Contact Person    39-523-490-872      
Arcispedale S. Maria Nuova Recruiting
Reggio Emilia, Italy, 42100
Contact: Contact Person    39-0522-296-623      
Cellulari ed Ematologia Sapienza Recruiting
Roma, Italy, 00161
Contact: Contact Person    49-6-857-951      
Sponsors and Collaborators
German High-Grade Non-Hodgkin's Lymphoma Study Group
Investigators
Study Chair: Michael G.M. Pfreundschuh, MD Universitaetsklinikum des Saarlandes
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00278421     History of Changes
Other Study ID Numbers: CDR0000459685, DSHNHL-2004-2, EU-205110, EUDRACT-2005-00521738, DSHNHL-FLYER-6664
Study First Received: January 16, 2006
Last Updated: April 16, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 3 follicular lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult diffuse mixed cell lymphoma
nodal marginal zone B-cell lymphoma
anaplastic large cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II mantle cell lymphoma
stage I adult Burkitt lymphoma
stage I mantle cell lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II marginal zone lymphoma
stage I marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 18, 2014