Clinical trial NCT00281918: Fludarabine and Cyclophosphamide With or Without Rituximab in Patients With Previously Untreated Chronic B-Cell Lymphocytic Leukemia
Official title: Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Chemotherapy With Fludarabine and Cyclophosphamide (FC) Alone in Patients With Previously Untreated Chronic Lymphocytic Leukaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia
Keywords: B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: German CLL Study Group
First posted: 2006-01-25
Enrollment: 817
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared to fludarabine and cyclophosphamide in treating patients with B-cell chronic lymphocytic leukemia.


Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosed B-cell chronic lymphocytic leukemia (CLL) defined by the National Cancer Institute (NCI) Working Group criteria
* Meets 1 of the following criteria:

  * Binet stage C disease
  * Binet stage B disease AND ≥ 1 of the following signs or symptoms\*:

    * B symptoms (night sweats, weight loss ≥ 10% within the previous 6 months, fevers \> 38°C or 100.4°F for ≥ 2 weeks without evidence of infection), or constitutional symptoms (fatigue)
    * Continuous progression (doubling of peripheral lymphocyte count within the past 6 months and absolute lymphocyte count \> 50 G/I)
    * Evidence of progressive marrow failure as manifested by the development/worsening of anemia and/or thrombocytopenia
    * Massive, progressive or painful splenomegaly or hypersplenism
    * Massive lymph nodes or lymph node clusters (\> 10 cm in longest diameter), danger of organ complications through large lymphoma (e.g., vascular compression or tracheal narrowing), or progressive lymphadenopathy
    * Occurrence of symptomatic hyperviscosity problems at leukocyte counts \> 200 G/I (symptomatic leukostasis) NOTE: \* Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for eligibility
* No Binet stage A disease
* No transformation to an aggressive B-cell malignancy (e.g., diffuse large cell lymphoma, Richter's syndrome, or prolymphocytic leukemia)

PATIENT CHARACTERISTICS:

* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Cumulative Illness Rating Scale (CIRS) score \> 6
* Life expectancy \> 6 months
* Bilirubin ≤ 2 times upper limit of normal (ULN)
* Alkaline phosphatase and transaminases ≤ 2 times ULN
* Creatinine clearance ≥ 70 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 2 months after study treatment
* No known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs
* No cerebral dysfunction that precludes chemotherapy
* No active bacterial, viral, or fungal infection
* No clinically significant autoimmune cytopenia or Coombs-positive hemolytic anemia
* No other active malignancy requiring concurrent treatment except basal cell carcinoma or tumors treated curatively by surgery
* No medical or psychological condition that would preclude study therapy
* No concurrent disease that requires prolonged (\> 1 month) therapy involving glucocorticoids

PRIOR CONCURRENT THERAPY:

* No previous treatment of CLL by chemotherapy, radiotherapy, or immunotherapy

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Median observation time at time of analysis was approximately 21 months
measure: Final Analysis: Time to Progression-free Survival Event
timeFrame: Median observation time was approximately 66.4 months
Secondary outcomes:
measure: Event-free Survival (EFS)
timeFrame: Median observation time at time of analysis was approximately 21 months
measure: Overall Survival (OS)
timeFrame: Median observation time at time of analysis was approximately 21 months
measure: Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).
timeFrame: Median observation time at time of analysis was approximately 21 months
measure: Final Analysis: Time to Overall Survival Event
timeFrame: Median observation time was approximately 66.4 months
measure: Final Analysis: Time to Event-free Survival Event
timeFrame: Median observation time was approximately 66.4 months
measure: Final Analysis: Time to Disease-free Survival (DFS) Event in Participants With Complete Response (CR)
timeFrame: Median observation time was approximately 66.4 months
measure: Final Analysis: Duration of Response
timeFrame: Median observation time was approximately 66.4 months
measure: Final Analysis: Percentage of Participants With Complete Response (CR) and Partial Response
timeFrame: Median observation time was approximately 66.4 months
measure: Final Analysis: Time to New Treatment for Chronic Lymphocytic Leukemia(CLL)
timeFrame: Median observation time was approximately 66.4 months
Other outcomes:
Locations:
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Westmead - Wentworthville
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Vienna
country: Austria
facility: Hanuschkrankenhaus
city: Vienna
country: Austria
facility: Rudolfinerhaus
city: Wien
country: Austria
facility: Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Mont-Godinne Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: Brno
country: Czech Republic
facility: Masaryk University Hospital
city: Hradec Kralove
country: Czech Republic
facility: Fakultni Nemocnice Hradec Kralove
city: Olomouc
country: Czech Republic
facility: University Hospital - Olomouc
city: Pilsen-Lochotin
country: Czech Republic
facility: University Hospital in Pilsen - Lochotin
city: Prague
country: Czech Republic
facility: First Medical Clinic of Charles University Hospital
city: Copenhagen
country: Denmark
facility: Copenhagen County Herlev University Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
city: Saint Priest en Jarez
country: France
facility: Institut de Cancerologie de la Loire
city: Ahaus
country: Germany
facility: Praxis Fur Hamatologie und Onkologie Ahaus
city: Ansbach
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
city: Augsburg
country: Germany
facility: Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Bayreuth
country: Germany
facility: Internistische Praxis - Bayreuth
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Bielefeld
country: Germany
facility: Onkologische Schwerpunktpraxis Bielefeld
city: Bietigheim
country: Germany
facility: Krankenhaus Bietigheim
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt gGmbH
city: Bottrop
country: Germany
facility: Marienhospital Bottrop gGmbH
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Burglengenfeld
country: Germany
facility: Krankenhaus Burglengenfeld
city: Coesfeld
country: Germany
facility: Onkologische Schwerpunktpraxis at Facharzt fuer Innere Medizin
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: Onkologische Schwerpunktpraxis
city: Dresden
country: Germany
facility: Onkologische Gemeinschaftspraxis - Dresden
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Dusseldorf
country: Germany
facility: Internistische Praxis - Dusseldorf
city: Dusseldorf
country: Germany
facility: Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth
city: Dusseldorf
country: Germany
facility: Krankenhaus Benrath
city: Eisenach
country: Germany
facility: St. Georg Klinikum Eisenach GmbH
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Erfurt
country: Germany
facility: Internistiche Praxis
city: Erlangen
country: Germany
facility: Onkologische Schwerpunkt Praxis
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Essen
country: Germany
facility: Evangelisches Krankenhaus Essen Werden
city: Esslingen
country: Germany
facility: Staedtische Kliniken Esslingen
city: Forchheim
country: Germany
facility: Internistische Gemeinschaftspraxis - Forchheim
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Frankfurt
country: Germany
facility: Staedtische Kliniken Frankfurt am Main - Hoechst
city: Freiburg
country: Germany
facility: Gemeinschaftspraxis - Freiburg
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch - Partenkirchen GmbH
city: Gerlingen
country: Germany
facility: Internistische Praxis - Gerlingen
city: Giessen
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
city: Goettingen
country: Germany
facility: Universitaetsklinikum Goettingen
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Hagen
country: Germany
facility: St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
city: Halle
country: Germany
facility: Internistische Praxis - Halle
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Hamm
country: Germany
facility: St. Marien-Hospital Hamm - Klinik Knappenstrasse
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Herne
country: Germany
facility: Marienhospital at Ruhr University Bochum
city: Herrsching
country: Germany
facility: Privatklinik Dr. R. Schindlbeck GmbH & Co. KG
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Jena
country: Germany
facility: Gemeinschaftspraxis Innere Medizin
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Karlsruhe
country: Germany
facility: St. Vincentius-Kliniken
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kempten
country: Germany
facility: Klinikum Kempten Oberallgaeu
city: Kiel
country: Germany
facility: Internistische Praxis - Kiel
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein - Kiel Campus
city: Koblenz
country: Germany
facility: Praxis fuer Haematologie und Onkologie
city: Koblez
country: Germany
facility: Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Landshut
country: Germany
facility: Klinikum Landshut
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Leipzig
country: Germany
facility: Klinikum "St. Georg" Leipzig
city: Lemgo
country: Germany
facility: Klinikum Lippe - Lemgo
city: Loerrach
country: Germany
facility: Internistische Praxis - Loerrach
city: Ludwigshafen
country: Germany
facility: Gemeinschaftspraxis - Ludwigshafen
city: Luebeck
country: Germany
facility: Sana Kliniken Luebeck
city: Magdeburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Magdeburg
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: Universitatsklinik Mainz
city: Mannheim
country: Germany
facility: III Medizinische Klinik Mannheim
city: Moenchengladbach
country: Germany
facility: Krankenhaus Maria Hilf GmbH
city: Muenchen
country: Germany
facility: Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
city: Muenster
country: Germany
facility: University of Muenster
city: Muenster
country: Germany
facility: Haematologisch - Onkologische Gemeinschaftspraxis
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Staedtisches Krankenhaus Muenchen - Harlaching
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Munich
country: Germany
facility: Haematologische Schwerpunktpraxis
city: Neunkirchen
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Schmidt
city: Norderstedt
country: Germany
facility: Praxis fuer Haematologie und Interne Onkologie
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Oberhausen
country: Germany
facility: Gemeinschaftspraxis - Oberhausen
city: Offenbach
country: Germany
facility: Internistische Gemeinschaftspraxis - Offenbach
city: Oldenburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Oldenburg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Pasewalk
country: Germany
facility: Asklepios Klinik Pasewalk
city: Pforzheim
country: Germany
facility: Municipal Hospital Complex
city: Potsdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Recklinghausen
country: Germany
facility: Elisabeth Krankenhaus
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Sanderbusch
country: Germany
facility: Nordwestkrankenhaus Sanderbusch
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Stuttgart
country: Germany
facility: Internistische Gemeinschaftspraxis - Stuttgart
city: Stuttgart
country: Germany
facility: Haematologische Praxis
city: Stuttgart
country: Germany
facility: Klinik fuer Onkologie - Katharinenhospital Stuttgart
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Torgau
country: Germany
facility: KKH Torgau
city: Trier
country: Germany
facility: Onkologische Gemeinschaftspraxis - Trier
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Troisdorf
country: Germany
facility: Praxis Fuer Internistische Haematologie / Onkologie
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Municipal Hospital Complex
city: Wanzleben
country: Germany
facility: Praxis fur Innere Medizin - Wanzleben
city: Weiden
country: Germany
facility: Haematologische Praxis
city: Wesel
country: Germany
facility: Schwerpunktpraxis Hamatologie/Onkologie - Wesel
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Wuerzburg
country: Germany
facility: Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
city: Wuppertal 2
country: Germany
facility: Kliniken St. Antonius
city: Wurzburg
country: Germany
facility: Hamatologisch - Onkologische Praxis Wurzburg
city: Beer-Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: BNAI Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Kfar Saba
country: Israel
facility: Riverview Cancer Care Medical Associates, PC
city: Rehovot
country: Israel
facility: Kaplan Hospital
city: Cagliari
country: Italy
facility: Ospedale Oncologico A. Businco
city: Milano
country: Italy
facility: Fondazione Centro San Raffaele Del Monte Tabor
city: Perugia
country: Italy
facility: Perugia Regional Cancer Center
city: Rome
country: Italy
facility: Ospedale Sant' Eugenio
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Canterbury Health Laboratories
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Toledo
country: Spain
facility: Hospital Virgen Del La Salud
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Michael Hallek, MD
role: STUDY_CHAIR
References:
citation: Bloehdorn J, Krzykalla J, Holzmann K, Gerhardinger A, Jebaraj BMC, Bahlo J, Humphrey K, Tausch E, Robrecht S, Mertens D, Schneider C, Fischer K, Hallek M, Dohner H, Benner A, Stilgenbauer S. Integrative prognostic models predict long-term survival after immunochemotherapy in chronic lymphocytic leukemia patients. Haematologica. 2022 Mar 1;107(3):615-624. doi: 10.3324/haematol.2020.251561.
citation: Jaramillo S, Agathangelidis A, Schneider C, Bahlo J, Robrecht S, Tausch E, Bloehdorn J, Hoechstetter M, Fischer K, Eichhorst B, Goede V, Hallek M, Dohner H, Rosenquist R, Ghia P, Stamatopoulos K, Stilgenbauer S. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG). Haematologica. 2020 Nov 1;105(11):2598-2607. doi: 10.3324/haematol.2019.231027.
citation: Kreuzberger N, Damen JA, Trivella M, Estcourt LJ, Aldin A, Umlauff L, Vazquez-Montes MD, Wolff R, Moons KG, Monsef I, Foroutan F, Kreuzer KA, Skoetz N. Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis. Cochrane Database Syst Rev. 2020 Jul 31;7(7):CD012022. doi: 10.1002/14651858.CD012022.pub2.
citation: Dimier N, Delmar P, Ward C, Morariu-Zamfir R, Fingerle-Rowson G, Bahlo J, Fischer K, Eichhorst B, Goede V, van Dongen JJM, Ritgen M, Bottcher S, Langerak AW, Kneba M, Hallek M. A model for predicting effect of treatment on progression-free survival using MRD as a surrogate end point in CLL. Blood. 2018 Mar 1;131(9):955-962. doi: 10.1182/blood-2017-06-792333. Epub 2017 Dec 18.
citation: Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, Langerbeins P, von Tresckow J, Engelke A, Maurer C, Kovacs G, Herling M, Tausch E, Kreuzer KA, Eichhorst B, Bottcher S, Seymour JF, Ghia P, Marlton P, Kneba M, Wendtner CM, Dohner H, Stilgenbauer S, Hallek M. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016 Jan 14;127(2):208-15. doi: 10.1182/blood-2015-06-651125. Epub 2015 Oct 20.
citation: Weisser M, Yeh RF, Duchateau-Nguyen G, Palermo G, Nguyen TQ, Shi X, Stinson SY, Yu N, Dufour A, Robak T, Salogub GN, Dmoszynska A, Solal-Celigny P, Warzocha K, Loscertales J, Catalano J, Larratt L, Rossiev VA, Bence-Bruckler I, Geisler CH, Montillo M, Fischer K, Fink AM, Hallek M, Bloehdorn J, Busch R, Benner A, Dohner H, Valente N, Wenger MK, Stilgenbauer S, Dornan D. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia. Blood. 2014 Jul 17;124(3):420-5. doi: 10.1182/blood-2013-12-538975. Epub 2014 Jun 10.
citation: Pflug N, Bahlo J, Shanafelt TD, Eichhorst BF, Bergmann MA, Elter T, Bauer K, Malchau G, Rabe KG, Stilgenbauer S, Dohner H, Jager U, Eckart MJ, Hopfinger G, Busch R, Fink AM, Wendtner CM, Fischer K, Kay NE, Hallek M. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014 Jul 3;124(1):49-62. doi: 10.1182/blood-2014-02-556399. Epub 2014 May 5.
citation: Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Dohner K, Buhler A, Bottcher S, Ritgen M, Kneba M, Winkler D, Tausch E, Hoth P, Edelmann J, Mertens D, Bullinger L, Bergmann M, Kless S, Mack S, Jager U, Patten N, Wu L, Wenger MK, Fingerle-Rowson G, Lichter P, Cazzola M, Wendtner CM, Fink AM, Fischer K, Busch R, Hallek M, Dohner H. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014 May 22;123(21):3247-54. doi: 10.1182/blood-2014-01-546150. Epub 2014 Mar 20.
citation: Eichhorst BF, Fischer K, Fink AM, Elter T, Wendtner CM, Goede V, Bergmann M, Stilgenbauer S, Hopfinger G, Ritgen M, Bahlo J, Busch R, Hallek M; German CLL Study Group (GCLLSG). Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis. Blood. 2011 Feb 10;117(6):1817-21. doi: 10.1182/blood-2010-04-282228. Epub 2010 Dec 7.
citation: Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grunhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jager U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Buhler A, Winkler D, Zenz T, Bottcher S, Ritgen M, Mendila M, Kneba M, Dohner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2;376(9747):1164-74. doi: 10.1016/S0140-6736(10)61381-5.