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

Lymphoma Clinical Trial

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00278421
• Other study ID #: CDR0000459685
• Secondary ID: DSHNHL-2004-2EU-
• Status: Completed
• Phase: Phase 3
• Start date: November 2005
• Est. completion date: August 2018

Study information

• Verified date: March 2021
• Source: German High-Grade Non-Hodgkin's Lymphoma Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 592
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• rituximab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• prednisone

• vincristine sulfate

Locations

Country	Name	City	State
Germany	Haematologisch Onkologische Praxis	Aachen
Germany	Klinikum Augsburg	Augsburg
Germany	Klinikum Bayreuth	Bayreuth
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Haematologisch-Onkologische Schwerpunktpraxis - Weilheim	Berlin
Germany	Franziskus Hospital	Bielefeld
Germany	Augusta-Kranken-Anstalt gGmbH	Bochum
Germany	Staedtisches Klinikum Braunschweig	Braunschweig
Germany	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen
Germany	Hospital Kuchwald Chemnitz	Chemnitz
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Praxis Fuer Haematologie Internistische Onkologie	Cologne
Germany	Carl - Thiem - Klinkum Cottbus	Cottbus
Germany	Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke	Damme
Germany	Klinikum Dortmund	Dortmund
Germany	Hans - Susemihl - Krankenhaus	Emden
Germany	St. Antonius Hospital	Eschweiler
Germany	Universitaetsklinikum Essen	Essen
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Klinikum Fulda	Fulda
Germany	Saint Josef Hospital	Gelsenkirchen
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Kreiskrankenhaus Gummersbach GMBH	Gummersbach
Germany	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen
Germany	St. Sixtus Hospital	Haltern
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	University Medical Center Hamburg - Eppendorf	Hamburg
Germany	Evangelische Krankenhaus Hamm	Hamm
Germany	St. Marien-Hospital Hamm - Klinik Knappenstrasse	Hamm
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg
Germany	St. Bernward Krankenhaus	Hildesheim
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Clinic for Bone Marrow Transplantation and Hematology and Oncology	Idar-Oberstein
Germany	St. Vincentius - Kliniken	Karlsruhe
Germany	Staedtisches Klinikum Karlsruhe gGmbH	Karlsruhe
Germany	Klinikum Kempten Oberallgaeu	Kempten
Germany	University Hospital Schleswig-Holstein - Kiel Campus	Kiel
Germany	Caritas - Krakenhaus Lebach	Lebach
Germany	Klinikum Lippe - Lemgo	Lemgo
Germany	St. Vincenz Hospital Limburg	Limburg
Germany	Klinikum der Stadt Ludwigshafen am Rhein	Ludwigshafen am Rhein
Germany	Kreiskrankenhaus Luedenscheid	Luedenscheid
Germany	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	III Medizinische Klinik Mannheim	Mannheim
Germany	Universitaetsklinikum Giessen und Marburg GmbH - Marburg	Marburg
Germany	Krankenhaus Ludmillenstift	Meppen
Germany	Krankenhaus Maria Hilf GmbH	Moenchengladbach
Germany	Haematologisch - Onkologische Gemeinschaftspraxis - Muenster	Muenster
Germany	Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster	Muenster
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Klinikum Schwaebisch Gmuend Stauferklinik	Mutlangen
Germany	Onkologische Schwerwpunktpraxis Dr. Ladda	Neumarkt
Germany	Lukaskrankenhaus Neuss	Neuss
Germany	Schlossbergkliniken Oberstaufen	Oberstaufen
Germany	Klinikum Oldenburg	Oldenburg
Germany	Klinikum Ernst Von Bergmann	Potsdam
Germany	Prosper-Hospital Recklinghausen	Recklinghausen
Germany	St. Marien - Krankenhaus Siegen GMBH	Siegen
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Krankenanstalt Mutterhaus der Borromaerinnen	Trier
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	St. Marienhospital - Vechta	Vechta
Germany	Onkologische Schwerpunktpraxis	Wendlingen
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Helios Kliniken Wuppertal University Hospital	Wuppertal
Israel	Rabin Medical Center - Beilinson Campus	Petah-Tikva
Italy	Ospedale Civile - Piacenza	Piacenza
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	Cellulari ed Ematologia Sapienza	Roma

Sponsors (1)

Lead Sponsor	Collaborator
German High-Grade Non-Hodgkin's Lymphoma Study Group

Countries where clinical trial is conducted

Germany,  Israel,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		through study completion
Secondary	Complete response (CR) rate duration until first relapse		through study completion
Secondary	Progression rate during treatment		through study completion
Secondary	Survival		through study completion
Secondary	Tumor control measured from day 1 of course 1 of CHOP therapy (non-tumor related events are censored)		through study completion
Secondary	Disease-free survival measured from day 1 of course 1 of CHOP therapy		through study completion
Secondary	Safety (adverse events, serious adverse events) assessed at 3 months after treatment		through study completion