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LymphomaPhase 3NCT00278421

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

A Phase 3 study testing rituximab, cyclophosphamide and doxorubicin hydrochloride in people with Lymphoma, run by German High-Grade Non-Hodgkin's Lymphoma Study Group at 78 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Lymphoma
What is being tested?
rituximab, cyclophosphamide and doxorubicin hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
592 participants
Where
78 sitesin 3 countries
Study dates
Nov 2005to Aug 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

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

Trial locations and contacts

78 sites in 3 countries.

78 sites in 3 countries

Germany74 sites

  • Haematologisch Onkologische Praxis

    Aachen, 52070

  • Klinikum Augsburg

    Augsburg, DOH-86156

  • Klinikum Bayreuth

    Bayreuth, D-95445

  • Haematologisch-Onkologische Schwerpunktpraxis - Weilheim

    Berlin, 13357

  • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

    Berlin, D-12200

  • Franziskus Hospital

    Bielefeld, D-33615

  • Augusta-Kranken-Anstalt gGmbH

    Bochum, D-44791

  • Staedtisches Klinikum Braunschweig

    Braunschweig, G-38114

  • DIAKO Ev. Diakonie Krankenhaus gGmbH

    Bremen, D-28239

  • Hospital Kuchwald Chemnitz

    Chemnitz, D-09113

  • Praxis Fuer Haematologie Internistische Onkologie

    Cologne, D-50677

  • Medizinische Universitaetsklinik I at the University of Cologne

    Cologne, D-50924

  • Carl - Thiem - Klinkum Cottbus

    Cottbus, D-03048

  • Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke

    Damme, D-49401

  • Klinikum Dortmund

    Dortmund, D-44137

  • Hans - Susemihl - Krankenhaus

    Emden, 26721

  • St. Antonius Hospital

    Eschweiler, DOH-52249

  • Universitaetsklinikum Essen

    Essen, D-45122

  • Klinikum Frankfurt (Oder) GmbH

    Frankfurt (Oder), D-15236

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, D-79106

  • Klinikum Fulda

    Fulda, D-36013

  • Saint Josef Hospital

    Gelsenkirchen, D-45899

  • Universitaetsklinikum Goettingen

    Göttingen, D-37075

  • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

    Greifswald, D-17475

  • Kreiskrankenhaus Gummersbach GMBH

    Gummersbach, D-51643

  • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

    Hagen, D-58095

  • St. Sixtus Hospital

    Haltern, D-45721

  • Asklepios Klinik St. Georg

    Hamburg, D-20099

  • University Medical Center Hamburg - Eppendorf

    Hamburg, D-20246

  • Haematologisch-Onkologische Praxis Altona

    Hamburg, D-22767

  • St. Marien-Hospital Hamm - Klinik Knappenstrasse

    Hamm, D-59071

  • Evangelische Krankenhaus Hamm

    Hamm, DOH-59063

  • Medizinische Hochschule Hannover

    Hanover, D-30625

  • Ruprecht - Karls - Universitaet Heidelberg

    Heidelberg, 69115

  • St. Bernward Krankenhaus

    Hildesheim, D-31134

  • Universitaetsklinikum des Saarlandes

    Homburg, D-66424

  • Clinic for Bone Marrow Transplantation and Hematology and Oncology

    Idar-Oberstein, D-55743

  • Staedtisches Klinikum Karlsruhe gGmbH

    Karlsruhe, 76133

  • St. Vincentius - Kliniken

    Karlsruhe, D-76137

  • Klinikum Kempten Oberallgaeu

    Kempten, D-87439

  • University Hospital Schleswig-Holstein - Kiel Campus

    Kiel, D-24116

  • Caritas - Krakenhaus Lebach

    Lebach, 66822

  • Klinikum Lippe - Lemgo

    Lemgo, D-32657

  • St. Vincenz Hospital Limburg

    Limburg, D-65549

  • Kreiskrankenhaus Luedenscheid

    Lüdenscheid, 58515

  • Klinikum der Stadt Ludwigshafen am Rhein

    Ludwigshafen am Rhein, D-67063

  • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

    Magdeburg, D-39120

  • III Medizinische Klinik Mannheim

    Mannheim, D-68305

  • Universitaetsklinikum Giessen und Marburg GmbH - Marburg

    Marburg, D-35033

  • Krankenhaus Ludmillenstift

    Meppen, 49716

  • Krankenhaus Maria Hilf GmbH

    Mönchengladbach, D-41063

  • Klinikum der Universitaet Muenchen - Grosshadern Campus

    Munich, D-81377

  • Klinikum Rechts Der Isar - Technische Universitaet Muenchen

    Munich, D-81675

  • Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

    Münster, D-48149

  • Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster

    Münster, D-48149

  • Klinikum Schwaebisch Gmuend Stauferklinik

    Mutlangen, D-73557

  • Onkologische Schwerwpunktpraxis Dr. Ladda

    Neumarkt, D-92318

  • Lukaskrankenhaus Neuss

    Neuss, D-41464

  • Schlossbergkliniken Oberstaufen

    Oberstaufen, D-87534

  • Klinikum Oldenburg

    Oldenburg, D-26133

  • Study site

    Pforzheim, 75179

  • Klinikum Ernst Von Bergmann

    Potsdam, D-14467

  • Prosper-Hospital Recklinghausen

    Recklinghausen, DOH-45659

  • Study site

    Rostock, D-18257

  • St. Marien - Krankenhaus Siegen GMBH

    Siegen, D-57072

  • Diakonie Klinikum Stuttgart

    Stuttgart, D-70176

  • Krankenanstalt Mutterhaus der Borromaerinnen

    Trier, D-54219

  • Southwest German Cancer Center at Eberhard-Karls-University

    Tübingen, D-72076

  • Universitaetsklinikum Tuebingen

    Tübingen, D-72076

  • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

    Ulm, D-89081

  • St. Marienhospital - Vechta

    Vechta, D-49377

  • Onkologische Schwerpunktpraxis

    Wendlingen, 73240

  • Dr. Horst-Schmidt-Kliniken

    Wiesbaden, D-65199

  • Helios Kliniken Wuppertal University Hospital

    Wuppertal, D-42283

Other trials in Germany

Italy3 sites

  • Ospedale Civile - Piacenza

    Piacenza, 29100

  • Arcispedale S. Maria Nuova

    Reggio Emilia, 42100

  • Cellulari ed Ematologia Sapienza

    Roma, 00161

Other trials in Italy

Israel1 site

  • Rabin Medical Center - Beilinson Campus

    Petah Tikva, 49100

Other trials in Israel

About this study

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]

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.

Read the 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.

Conditions
Lymphoma
Keywords
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
Medical subject headings
Lymphoma, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large-Cell, Anaplastic, Lymphoma, Large-Cell, Immunoblastic, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00278421
Study groupRoleWhat they receive
Interventional: 6 R-CHOP-21Active comparatorArm 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.
Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate
Interventional: 4 R-CHOP-21 + 2 x RActive comparatorArm 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.
Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: through study completion

Secondary outcomes (6)

  1. Complete response (CR) rate duration until first relapse

    Measured: through study completion

  2. Progression rate during treatment

    Measured: through study completion

  3. Survival

    Measured: through study completion

  4. Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored)

    Measured: through study completion

  5. Disease-free survival measured from day 1 of course 1 of CHOP therapy

    Measured: through study completion

  6. Safety (adverse events, serious adverse events) assessed at 3 months after treatment

    Measured: through study completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2006 (estimated)
  2. Study startNov 2005
  3. Primary completionAug 2018
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
592 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00278421
Sponsor's protocol ID
CDR0000459685
Other IDs
DSHNHL-2004-2, EU-205110, EUDRACT-2005-00521738, DSHNHL-FLYER-6664
Status last verified
Mar 2021
First submitted
16 Jan 2006
Last updated
11 Mar 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. doi: 10.1016/S0140-6736(19)33008-9.

    PubMed 31868632

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rituximab, cyclophosphamide and doxorubicin hydrochloride in people with Lymphoma, run by German High-Grade Non-Hodgkin's Lymphoma Study Group at 78 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 78 sites in Germany, Italy, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00278421, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2021.

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