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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
German High-Grade Non-Hodgkin's Lymphoma Study Group
ClinicalTrials.gov Identifier:
NCT00278421
First received: January 16, 2006
Last updated: October 25, 2016
Last verified: November 2015
  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
Intervention Model: Parallel Assignment
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 German High-Grade Non-Hodgkin's Lymphoma Study Group:

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 [ Time Frame: through study completion ]

Secondary Outcome Measures:
  • Complete response (CR) rate duration until first relapse [ Time Frame: through study completion ]
  • Progression rate during treatment [ Time Frame: through study completion ]
  • Survival [ Time Frame: through study completion ]
  • Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored) [ Time Frame: through study completion ]
  • Disease-free survival measured from day 1 of course 1 of CHOP therapy [ Time Frame: through study completion ]
  • Safety (adverse events, serious adverse events) assessed at 3 months after treatment [ Time Frame: through study completion ]

Enrollment: 592
Study Start Date: November 2005
Study Completion Date: October 2016
Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Interventional: 6 R-CHOP-21
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.
Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate
Active Comparator: Interventional: 4 R-CHOP-21 + 2 x R
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.
Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate

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   (Adult)
Sexes Eligible for Study:   All
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
Aachen, Germany, 52070
Klinikum Augsburg
Augsburg, Germany, DOH-86156
Klinikum Bayreuth
Bayreuth, Germany, D-95445
Haematologisch-Onkologische Schwerpunktpraxis - Weilheim
Berlin, Germany, 13357
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany, D-12200
Franziskus Hospital
Bielefeld, Germany, D-33615
Augusta-Kranken-Anstalt gGmbH
Bochum, Germany, D-44791
Staedtisches Klinikum Braunschweig
Braunschweig, Germany, G-38114
DIAKO Ev. Diakonie Krankenhaus gGmbH
Bremen, Germany, D-28239
Hospital Kuchwald Chemnitz
Chemnitz, Germany, D-09113
Praxis Fuer Haematologie Internistische Onkologie
Cologne, Germany, D-50677
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, Germany, D-50924
Carl - Thiem - Klinkum Cottbus
Cottbus, Germany, D-03048
Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke
Damme, Germany, D-49401
Klinikum Dortmund
Dortmund, Germany, D-44137
Hans - Susemihl - Krankenhaus
Emden, Germany, 26721
St. Antonius Hospital
Eschweiler, Germany, DOH-52249
Universitaetsklinikum Essen
Essen, Germany, D-45122
Klinikum Frankfurt (Oder) GmbH
Frankfurt (Oder), Germany, D-15236
Universitaetsklinikum Freiburg
Freiburg, Germany, D-79106
Klinikum Fulda
Fulda, Germany, D-36013
Saint Josef Hospital
Gelsenkirchen, Germany, D-45899
Universitaetsklinikum Goettingen
Goettingen, Germany, D-37075
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
Greifswald, Germany, D-17475
Kreiskrankenhaus Gummersbach GMBH
Gummersbach, Germany, D-51643
St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
Hagen, Germany, D-58095
St. Sixtus Hospital
Haltern, Germany, D-45721
Asklepios Klinik St. Georg
Hamburg, Germany, D-20099
University Medical Center Hamburg - Eppendorf
Hamburg, Germany, D-20246
Haematologisch-Onkologische Praxis Altona
Hamburg, Germany, D-22767
St. Marien-Hospital Hamm - Klinik Knappenstrasse
Hamm, Germany, D-59071
Evangelische Krankenhaus Hamm
Hamm, Germany, DOH-59063
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Ruprecht - Karls - Universitaet Heidelberg
Heidelberg, Germany, 69115
St. Bernward Krankenhaus
Hildesheim, Germany, D-31134
Universitaetsklinikum des Saarlandes
Homburg, Germany, D-66424
Clinic for Bone Marrow Transplantation and Hematology and Oncology
Idar-Oberstein, Germany, D-55743
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, Germany, 76133
St. Vincentius - Kliniken
Karlsruhe, Germany, D-76137
Klinikum Kempten Oberallgaeu
Kempten, Germany, D-87439
University Hospital Schleswig-Holstein - Kiel Campus
Kiel, Germany, D-24116
Caritas - Krakenhaus Lebach
Lebach, Germany, 66822
Klinikum Lippe - Lemgo
Lemgo, Germany, D-32657
St. Vincenz Hospital Limburg
Limburg, Germany, D-65549
Klinikum der Stadt Ludwigshafen am Rhein
Ludwigshafen am Rhein, Germany, D-67063
Kreiskrankenhaus Luedenscheid
Luedenscheid, Germany, 58515
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, Germany, D-39120
III Medizinische Klinik Mannheim
Mannheim, Germany, D-68305
Universitaetsklinikum Giessen und Marburg GmbH - Marburg
Marburg, Germany, D-35033
Krankenhaus Ludmillenstift
Meppen, Germany, 49716
Krankenhaus Maria Hilf GmbH
Moenchengladbach, Germany, D-41063
Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
Muenster, Germany, D-48149
Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
Muenster, Germany, D-48149
Klinikum der Universitaet Muenchen - Grosshadern Campus
Munich, Germany, D-81377
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Klinikum Schwaebisch Gmuend Stauferklinik
Mutlangen, Germany, D-73557
Onkologische Schwerwpunktpraxis Dr. Ladda
Neumarkt, Germany, D-92318
Lukaskrankenhaus Neuss
Neuss, Germany, D-41464
Schlossbergkliniken Oberstaufen
Oberstaufen, Germany, D-87534
Klinikum Oldenburg
Oldenburg, Germany, D-26133
Pforzheim, Germany, 75179
Klinikum Ernst Von Bergmann
Potsdam, Germany, D-14467
Prosper-Hospital Recklinghausen
Recklinghausen, Germany, DOH-45659
Rostock, Germany, D-18257
St. Marien - Krankenhaus Siegen GMBH
Siegen, Germany, D-57072
Diakonie Klinikum Stuttgart
Stuttgart, Germany, D-70176
Krankenanstalt Mutterhaus der Borromaerinnen
Trier, Germany, D-54219
Southwest German Cancer Center at Eberhard-Karls-University
Tuebingen, Germany, D-72076
Universitaetsklinikum Tuebingen
Tuebingen, Germany, D-72076
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, Germany, D-89081
St. Marienhospital - Vechta
Vechta, Germany, D-49377
Onkologische Schwerpunktpraxis
Wendlingen, Germany, 73240
Dr. Horst-Schmidt-Kliniken
Wiesbaden, Germany, D-65199
Helios Kliniken Wuppertal University Hospital
Wuppertal, Germany, D-42283
Israel
Rabin Medical Center - Beilinson Campus
Petah-Tikva, Israel, 49100
Italy
Ospedale Civile - Piacenza
Piacenza, Italy, 29100
Arcispedale S. Maria Nuova
Reggio Emilia, Italy, 42100
Cellulari ed Ematologia Sapienza
Roma, Italy, 00161
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

Responsible Party: German High-Grade Non-Hodgkin's Lymphoma Study Group
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: October 25, 2016

Keywords provided by German High-Grade Non-Hodgkin's Lymphoma Study Group:
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
Antirheumatic Agents
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
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on January 19, 2017