Clinical trial NCT00052936: Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma
Official title: Randomised Study Comparing 6 And 8 Cycles Of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine And Prednisone) At 14-Day Intervals (CHOP-14), Both With Or Without The Monoclonal Anti-CD20 Antibody Rituximab In Patients Aged 61 To 80 Years With Aggressive Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
stage III grade 1 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III grade 2 follicular lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage I adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
stage I marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 1506
Sex: ALL
Minimum age (years): 61
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide, doxorubicin, vincristine, and prednisone together with or without rituximab works in treating older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer randomized as of 6/2005).

Detailed description: OBJECTIVES:

Primary

* Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma.
* Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens.
* Compare the rate of complete remission, rate of primary progression, tumor control, disease-free survival, overall survival, and relapse after radiotherapy in patients treated with these regimens.
* Compare the safety and side effects of these regimens in these patients.

Secondary

* Compare short-term and long-term side effects of these regimens in these patients.
* Compare quality of life of patients treated with these regimens.
* Compare the cost of these regimens in these patients.
* Determine relapse in patients treated with these regimens who received involved-field radiotherapy.

OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label, multicenter study. Patients are stratified according to participating center, value for serum lactic dehydrogenase (no greater than upper limit of normal \[ULN\] vs greater than ULN), bulky disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0 or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms. Patients with CD20-negative lymphoma are randomized to arms I or II only.

* Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to day 0 before initiating CHOP chemotherapy.
* Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses.
* Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm I for a total of 8 courses.
* Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.
* Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery of bone marrow, and after complete remision of mucositis, patients with sites of initial bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) by an excisional biopsy of a lymph node or an extensive biopsy of an extranodal involvement (if there is no lymph node involvement)
* CD20\^+ B-cell lymphoma or CD20\^- B-cell and T-cell lymphoma allowed
* B-cell NHL including the following:

  * Stage III follicular lymphoma
  * Stage III follicular lymphoma and diffuse B-cell lymphoma
  * Lymphoblastic precursor B-cell lymphoma
  * Diffuse large cell B-cell lymphoma

    * Centroblastic
    * Immunoblastic
    * Plasmablastic
    * Anaplastic large cell
    * T-cell-rich B-cell lymphoma
    * Primary effusion lymphoma
    * Intravasal B-cell lymphoma
    * Primary mediastinal B-cell lymphoma
  * Mantle zone lymphoma, blastoid
  * Burkitt's lymphoma
  * Burkitt-like lymphoma
  * Aggressive marginal zone lymphoma (monocytoid)
* T-cell NHL including the following:

  * Lymphoblastic precursor T-cell lymphoma
  * Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS)

    * Lennert's lymphoma
    * T-zone lymphoma
  * T-cell lymphoma of the angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) type
  * Anaplastic large cell lymphoma

    * ALK\^+
    * ALK\^-
  * Extranodal NK/T-cell lymphoma, nasal type
  * Intestinal T/NK-cell lymphoma (with or without enteropathy)

    * Hepatosplenic gamma-delta lymphoma
    * Subcutaneous panniculitis-like PTCL
    * Aggressive T/NK PTCL
  * Anaplastic large-cell NHL, NOS
* Bone marrow involvement no more than 25%
* No lymphoma that is clearly restricted to the CNS or originating from the gastrointestinal tract

PATIENT CHARACTERISTICS:

Age

* 61 to 80

Performance status

* ECOG 0-2 OR
* Karnofsky 60-100%

Life expectancy

* Not specified

Hematopoietic

* WBC at least 2,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 2 times upper limit of normal (ULN)
* No active hepatitis infection

Renal

* Creatinine no greater than 2 times ULN

Cardiovascular

* No Canadian Cardiovascular Society class III or IV angina pectoris
* No New York Heart Association class III or IV cardiac failure
* Ejection fraction at least 50%
* Fractional shortenings at least 25% by echocardiography or nuclear medicine examination

Pulmonary

* FEV1 at least 50%
* Diffusion capacity at least 50%

Other

* No uncontrolled diabetes mellitus
* No known hypersensitivity to any study medications
* No other concurrent malignancy
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy

Surgery

* Not specified

Other

* Must not have already initiated lymphoma therapy (except for the prephase treatment specified for this study)
* No other concurrent lymphoma therapy
* No concurrent participation in another treatment study

Primary outcomes:
measure: Time to treatment failure at 3 years within the study and then periodically after study completion
timeFrame: 3 years within the study and then periodically after study completion
Secondary outcomes:
measure: Complete response rate at 3 years within the study and then periodically after study completion
timeFrame: 3 years within the study and then periodically after
measure: Progression rate
timeFrame: 3 years within the study and then periodically after
measure: Survival
timeFrame: 3 years within the study and then periodically after
measure: Tumor control
timeFrame: 3 years within the study and then periodically after
measure: Disease-free survival
timeFrame: 3 years within the study and then periodically after
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Haematologisch Onkologische Praxis
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Ansbach
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
city: Aschaffenburg
country: Germany
facility: II. Medizinische Klinik
city: Aschaffenburg
country: Germany
facility: Specialist Practice for Oncology
city: Augsburg
country: Germany
facility: Haematologische Praxis
city: Augsburg
country: Germany
facility: Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Aurich
country: Germany
facility: Kreiskrankenhaus Aurich
city: Bad Hersfeld
country: Germany
facility: Regional Hospital Bad Hersfeld
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Bayreuth
country: Germany
facility: Krankenhaus Hohe Warte Mediziniche Klinik
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
city: Berlin
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis
city: Bernburg
country: Germany
facility: Hospital Complex Bernburg
city: Bietigheim
country: Germany
facility: Krankenhaus Bietigheim
city: Bocholt
country: Germany
facility: Saint Agnes Hospital
city: Bochum
country: Germany
facility: Saint Josef Hospital
city: Bochum
country: Germany
facility: Knappschaft Krankenhaus
city: Bonn
country: Germany
facility: Medizinische Poliklinik
city: Bonn
country: Germany
facility: Rheinische Friedrich-Wilhelms-Universitat
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Bunde
country: Germany
facility: Medizinische Klinik Am Lukas - Krankenhaus
city: Celle
country: Germany
facility: General Hospital
city: Chemnitz
country: Germany
facility: Hospital Kuchwald Chemnitz
city: Cologne-Kalk
country: Germany
city: Cologne-Merheim
country: Germany
facility: Lung Clinic Cologne-Merheim
city: Cologne
country: Germany
facility: Praxis Fuer Haematologie Internistische Onkologie
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Cottbus
country: Germany
facility: Carl - Thiem - Klinkum Cottbus
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dortmund
country: Germany
facility: Saint Johannes Hospital Dortmund
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duisburg
country: Germany
facility: St. Johannes Hospital - Medical Klinik II
city: Dulmen
country: Germany
facility: Franz Hospital Dulmen
city: Dusseldorf
country: Germany
facility: Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth
city: Emden
country: Germany
facility: Hans - Susemihl - Krankenhaus
city: Erfurt
country: Germany
facility: Klinikum Erfurt
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt/Oder
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Freiburg
country: Germany
facility: Evang. Deaconess Hospital Freiburg
city: Fulda
country: Germany
facility: Municipal Hospital Complex
city: Gehrden
country: Germany
facility: Robert - Koch Hospital
city: Gießen
country: Germany
facility: Centre for Internal Medicine Gieben
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Gutersloh
country: Germany
facility: Staedtisches Klinikum Guetersloh
city: Göttingen
country: Germany
facility: Universitaetsklinikum Goettingen
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Hagen
country: Germany
facility: St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
city: Halle/Saale
country: Germany
facility: Krankenhaus St. Elisabeth und St. Barbara
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Hamburg
country: Germany
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Nord Heidberg
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus Altona
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Altona
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hannover
country: Germany
city: Hannover
country: Germany
facility: Henriettenstiftung Krankenhaus
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Harrislee
country: Germany
facility: Oncology Specialists Clinic
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Heidelberg
country: Germany
facility: Medizinische Universitaetsklinik und Poliklinik
city: Heidenheim
country: Germany
facility: Regional Hospital Heidenheim
city: Heilbronn
country: Germany
facility: Regional Hospital Am Plattenwald - Bad Friedrichshall
city: Herford
country: Germany
facility: Klinikum Herford
city: Herne
country: Germany
facility: Marienhospital at Ruhr University Bochum
city: Herrsching am Ammersee
country: Germany
facility: Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
city: Hildesheim
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Holzminden
country: Germany
facility: Evang. Hospital
city: Homburg
country: Germany
facility: Medical University Hospital Homburg
city: Hoyerswerda
country: Germany
facility: Hospital Complex Hoyerswerda
city: Jena
country: Germany
facility: Gemeinschaftspraxis Innere Medizin
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller Universitaet Jena
city: Kaiserslautern
country: Germany
facility: Municipal Hospital Complex of the University
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Kassel
country: Germany
facility: Red Cross Hospital Kassel
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH
city: Koblenz
country: Germany
facility: Praxis fuer Haematologie und Onkologie
city: Kornwestheim
country: Germany
facility: Leonardis Clinic
city: Krefeld
country: Germany
facility: Klinikum Krefeld GmbH
city: Kronach
country: Germany
facility: Frankenwald Klinik
city: Lebach
country: Germany
facility: Caritas - Krakenhaus Lebach
city: Leipzig
country: Germany
facility: University Leipzig Clinic of Internal Medicine
city: Leipzig
country: Germany
facility: Klinikum "St. Georg" Leipzig
city: Leipzig
country: Germany
city: Lemgo
country: Germany
facility: Klinikum Lippe - Lemgo
city: Limburg
country: Germany
facility: St. Vincenz Hospital Limburg
city: Lingen
country: Germany
facility: St. Bonifatius Hospital Lingen
city: Lippstadt
country: Germany
facility: Dreifaltigkeits Hospital
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Ludwigshafen
country: Germany
facility: St. Marien Hospital Ludwighafen
city: Ludwigshafen
country: Germany
facility: Municipal Complex of Ludwigshafen
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg - Altstadt
city: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Mannheim
country: Germany
facility: III Medizinische Klinik Mannheim
city: Marburg
country: Germany
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH - Marburg
city: Mayen
country: Germany
facility: Regional Hospital Mayen
city: Minden
country: Germany
facility: Klinikum Minden
city: Minden
country: Germany
city: Monchengladbach
country: Germany
facility: Ev. Hospital Bethesda
city: Monchengladbach
country: Germany
facility: Hospital Maria-Hilf II
city: Monchenglasbach/Rheydt
country: Germany
city: Mulheim/Ruhr
country: Germany
facility: Evangelisches Krankenhaus - Mulheim
city: Mulheim/Ruhr
country: Germany
facility: St. Marien Hospital - Muelheim an der Ruhr
city: Munchberg
country: Germany
facility: Kreiskrankenhaus Muenchberg
city: Munich
country: Germany
facility: Munich Oncologic Practice at Elisenhof
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Innenstadt Campus
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Municipal Hospital Munich
city: Munster
country: Germany
facility: Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
city: Neumarkt
country: Germany
facility: Regional Hospital Neumarkt
city: Neunkirchen
country: Germany
facility: Staedtisches Klinikum Neunkirchen gGmbH
city: Neuss
country: Germany
facility: Lukaskrankenhaus Neuss
city: Nuremberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Offenburg
country: Germany
facility: Klinikum Offenburg
city: Oldenburg
country: Germany
facility: Hematologische Praxis
city: Oldenburg
country: Germany
facility: Ev. Hospital Oldenburg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Osnabrück
country: Germany
facility: Paracelsus - Klinik Osnabrueck
city: Pforzheim
country: Germany
facility: Municipal Hospital Complex
city: Potsdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Radebeul
country: Germany
facility: Kreiskrankenhaus Radebeul
city: Ravensburg
country: Germany
facility: Krankenhaus St. Elisabeth - Ravensburg
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Regensburg
country: Germany
facility: Hematologische Onkologische Praxis
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Rheine
country: Germany
facility: Jakobi Krankenhaus
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock
city: Rostock
country: Germany
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Saarbruecken
country: Germany
facility: Schwerpunktpraxis fuer Haematologie und Onkologie
city: Saarlouis
country: Germany
facility: St. Elizabeth-Klinik Saarlouis
city: Schleswig
country: Germany
facility: Martin - Luther Hospital
city: Schwabisch Hall
country: Germany
facility: Deaconess Hospital
city: Schweinfurt
country: Germany
facility: Leopoldina - Krankenhaus
city: Siegen
country: Germany
facility: Evang. Jung-Stilling Hospital
city: Solingen
country: Germany
facility: St. Lukas - Clinic Solingen
city: Stuttgart
country: Germany
facility: Klinik fuer Onkologie - Katharinenhospital Stuttgart
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart - Buergerhospital
city: Stuttgart
country: Germany
facility: Hospital Bad Cannstatt
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Thuine
country: Germany
facility: St. Elisabeth Hospital Thuine
city: Traunstein
country: Germany
facility: Regional Hospital Traunstein
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Trier
country: Germany
city: Trier
country: Germany
facility: Krankenhaus Barmherzigen Brueder
city: Tutzing
country: Germany
facility: Hospital Tutzing
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Unna
country: Germany
facility: Ev. Hospital Unna
city: Vechta
country: Germany
facility: St. Marienhospital - Vechta
city: Villingen-Schwenningen
country: Germany
facility: Municipal Hospital Complex
city: Waldbrol
country: Germany
facility: Regional Hospital Waldbrol
city: Werden
country: Germany
facility: Evangelisches Krankenhaus Essen Werden
city: Wetzlar
country: Germany
facility: Hospital Wetzler
city: Wiesbaden
country: Germany
facility: Deutsche Klinik fuer Diagnostik
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Witten
country: Germany
facility: Ev. Hospital Witten-Herdecke
city: Wuppertal
country: Germany
facility: Kliniken St. Antonius
city: Wurzburg
country: Germany
facility: University Wurzburg
city: Zwickau
country: Germany
facility: Municipal Hospital Complex Zwickau
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Universitaetsklinikum des Saarlandes
name: Michael G.M. Pfreundschuh, MD
role: STUDY_CHAIR
References:
citation: Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15.
citation: Kuhnl A, Cunningham D, Counsell N, Hawkes EA, Qian W, Smith P, Chadwick N, Lawrie A, Mouncey P, Jack A, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Rosenwald A, Ott G, Horn H, Ziepert M, Pfreundschuh M, Linch D. Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial. Ann Oncol. 2017 Jul 1;28(7):1540-1546. doi: 10.1093/annonc/mdx128.
citation: Pfreundschuh M, Poeschel V, Zeynalova S, Hanel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. doi: 10.1200/JCO.2013.54.6861. Epub 2014 Nov 17.
citation: Bittenbring JT, Neumann F, Altmann B, Achenbach M, Reichrath J, Ziepert M, Geisel J, Regitz E, Held G, Pfreundschuh M. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol. 2014 Oct 10;32(29):3242-8. doi: 10.1200/JCO.2013.53.4537. Epub 2014 Aug 18.
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