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

March 9, 2021 updated by: German High-Grade Non-Hodgkin's Lymphoma Study Group

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]

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

592

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: cyclophosphamide
Drug: prednisone
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Biological: rituximab
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.
Drug: cyclophosphamide
Drug: prednisone
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Biological: rituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
through study completion

Secondary Outcome Measures

Outcome Measure
Time Frame
Survival
Time Frame: through study completion
through study completion
Complete response (CR) rate duration until first relapse
Time Frame: through study completion
through study completion
Progression rate during treatment
Time Frame: through study completion
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
through study completion
Disease-free survival measured from day 1 of course 1 of CHOP therapy
Time Frame: through study completion
through study completion
Safety (adverse events, serious adverse events) assessed at 3 months after treatment
Time Frame: through study completion
through study completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German High-Grade Non-Hodgkin's Lymphoma Study Group

Investigators

  • Study Chair: Michael G.M. Pfreundschuh, MD †, Universitaetsklinikum des Saarlandes
  • Study Director: Viola Poeschel, MD, Study Office Homburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

August 1, 2018

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

January 16, 2006

First Submitted That Met QC Criteria

January 16, 2006

First Posted (Estimate)

January 18, 2006

Study Record Updates

Last Update Posted (Actual)

March 11, 2021

Last Update Submitted That Met QC Criteria

March 9, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000459685
  • DSHNHL-2004-2
  • EU-205110
  • EUDRACT-2005-00521738
  • DSHNHL-FLYER-6664

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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