Clinical trial NCT00290667: Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma
Official title: 2-Weekly CHOP Chemotherapy With Dose-Dense Rituximab for the Treatment of Patients Aged 61 to 80 Years With Aggressive CD-20 Positive B-Cell Lymphomas: A Phase-II/Pharmacokinetic Study (CHOP-R-ESC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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 adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large 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 adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2006-02-13
Enrollment: 586
Sex: ALL
Minimum age (years): 61
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with previously untreated B-cell lymphoma.

Detailed description: OBJECTIVES:

Primary

* Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive B-cell lymphoma.
* To determine whether increased single-doses of rituximab for males can compensate their lower serum levels.
* Evaluate the safety and toxicity profile of this regimen in male patients.

Secondary

* Determine the rate of complete responses, primary progressions under therapy, event-free survival, progression-free survival, and overall survival in patients treated with this regimen.
* Determine the rate of primary progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. All patients undergo the following treatment.

* Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral prednisone on days -6 to 0.
* Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy proceed to salvage chemotherapy off study.

Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4 weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy proceed to salvage chemotherapy off study.

Patients are then stratified according to center, International Prognostic Index (1-2 vs 3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.

* Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
* Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.

Some patients undergo blood sample collection periodically during and after treatment for pharmacokinetic studies.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year therafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histological diagnosis of aggressive B-cell lymphoma

  * Previously untreated disease
  * Stage I-IV disease
* CD20-positive disease
* Any International Prognostic Index (IPI) score
* No secondary lymphoma after prior chemotherapy or radiotherapy
* No primary CNS lymphoma
* No primary gastrointestinal (MALT) lymphoma

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy ≥ 3 months
* AST and ALT ≤ 3 times normal unless related to lymphoma
* Bilirubin ≤ 2 mg/dL unless related to lymphoma
* Creatinine ≤ 2 times normal unless related to lymphoma
* Fertile patients must use effective contraception
* No known allergic reactions against foreign proteins
* No active infections requiring systemically administered antibiotics or antiviral medications
* No noncompensated heart failure
* No dilatative cardiomyopathy
* No coronary heart disease with ST-segment depression in ECG
* No myocardial infarction during the past 6 months
* No chronic lung disease with hypoxemia
* No severe noncompensated hypertension
* No severe noncompensated diabetes mellitus
* No clinical signs of cerebral dysfunction
* No severe psychiatric disease
* No known HIV infection
* No active chronic hepatitis B or C infection
* No other concurrent diseases that exclude the administration of therapy as outlined by the study protocol

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 12 weeks since prior clinical trial participation
* No prior participation in this study
* No prior therapy, including murine antibody, for this cancer
* No prior organ transplantation
* No concurrent response-adapted radiotherapy ("iceberg radiotherapy")
* No other concurrent anticancer chemotherapy or other study medication

Primary outcomes:
measure: Pharmacokinetics (in first 20 patients of each cohort with a distinct variation of the rituximab schedule) assessed on days -4, -1, 10, 29, 57, 99, 155, 239, 267, 295, 407, and 491 of treatment
timeFrame: -4 to 491 days of treatment
measure: Safety and treatment related deaths at 3 months after study completion
timeFrame: 3 months after study completion
measure: Toxicity assessed by NCI criteria, adverse events, serious adverse events, protocol adherence, and treatment-related deaths at 3 months after study completion
timeFrame: 3 months after study completion
Secondary outcomes:
measure: Time to treatment failure assessed at 2 years within the study and periodically thereafter
timeFrame: at 2 years within the study and periodically thereafterlif
measure: Complete response rate assessed at 2 years within the study and periodically thereafter
timeFrame: at 2 years within the study and periodically thereafter
measure: Progression rate
timeFrame: life-long
measure: Survival time
timeFrame: life-long
measure: Progression-free survival
timeFrame: life-long
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: University Hospital Brno
city: Prague 5
country: Czechia
facility: Charles University Hospital
city: Lyon
country: France
facility: Hopital Debrousse
city: Aachen
country: Germany
facility: Haematologisch Onkologische Praxis
city: Aalen
country: Germany
facility: Ostalb-Klinikum Aalen
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: Specialist Practice for Oncology
city: Aschaffenburg
country: Germany
facility: II. Medizinische Klinik
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: HELIOS Klinikum Bad Saarow
city: Bad Salzuflen
country: Germany
facility: Internistische Praxis - Bad Salzuflen
city: Bad Soden
country: Germany
facility: Onkologische Schwerpunktpraxis und Tagesklinik Dres
city: Bad Säckingen
country: Germany
facility: Kreiskrankenhaus Bad Saeckingen
city: Bad Urach
country: Germany
facility: Ermstalklinik Bad Urach
city: Bamberg
country: Germany
facility: Klinikum am Bamberg
city: Bayreuth
country: Germany
facility: Krankenhaus Hohe Warte Mediziniche Klinik
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth
city: Bergisch Gladbach
country: Germany
facility: Praxis Dr. med. Stefan Korsten
city: Berlin
country: Germany
facility: Onkologisches Versorgungszentrum Friedrichshain
city: Berlin
country: Germany
facility: DRK Kliniken Berlin - Koepenick
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis
city: Berlin
country: Germany
facility: Evang. Waldkrankenhaus Spandau
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Onkolog - Haematolog Schwerpunktpraxis
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukoelln
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
city: Bernburg
country: Germany
facility: Hospital Complex Bernburg
city: Bielefeld
country: Germany
facility: Franziskus Hospital
city: Bietigheim
country: Germany
facility: Krankenhaus Bietigheim
city: Bocholt
country: Germany
facility: Saint Agnes Hospital
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt gGmbH
city: Bochum
country: Germany
facility: St. Josef-Hospital - Bochum
city: Bochum
country: Germany
facility: Knappschaftskrankenhaus Bochum-Langendreer
city: Bonn
country: Germany
facility: Johanniter-Krankenhaus Bonn
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Bonn
country: Germany
facility: Medizinische Poliklinik
city: Borken
country: Germany
facility: Praxis fuer Haematologie und Internistische Onkologie - Borken
city: Bottrop
country: Germany
facility: Knappschaftskrankenhaus Bottrop
city: Brandenburg
country: Germany
facility: Hamatologische Sprechstunde
city: Braunschweig
country: Germany
facility: Staedtisches Klinikum Braunschweig
city: Bremen
country: Germany
facility: Praxis Dres. F.& G. Doering
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Bremerhaven
country: Germany
facility: St. Joseph Hospital
city: Bremerhaven
country: Germany
facility: Zentralkrankenhaus
city: Burgwedel
country: Germany
facility: Praxis fuer Haematologie und Onkologie - Burgwedel
city: Bünde
country: Germany
facility: Medizinische Klinik am Lukas - Krankenhaus
city: Celle
country: Germany
facility: General Hospital
city: Celle
country: Germany
facility: Onkologische Schwerpunktpraxis Celle
city: Chemnitz
country: Germany
facility: Hospital Kuchwald Chemnitz
city: Coburg
country: Germany
facility: Klinikum Coburg
city: Coesfeld
country: Germany
facility: Internistische Praxis - Coesfeld
city: Cologne-Merheim
country: Germany
facility: Lung Clinic Cologne-Merheim
city: Cologne
country: Germany
facility: Praxis Internistischer Onkologie und Haematologie - Koeln
city: Cologne
country: Germany
facility: Kliniken der Stadt Koeln gGmbH - Krankenhaus Holweide
city: Cologne
country: Germany
facility: Praxis fuer Onkologie - Kalk
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: Damme
country: Germany
facility: Praxis Dr. Rheinhold Siegmund - Dr. Matthias Penke
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dessau
country: Germany
facility: Staedtisches Klinikum Dessau
city: Detmold
country: Germany
facility: Internistische Praxis
city: Dortmund
country: Germany
facility: Saint Johannes Hospital Dortmund
city: Dortmund
country: Germany
facility: Klinikum Dortmund
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Duisburg
country: Germany
facility: Johanniter-Krankenhaus Rheinhausen GmbH
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: Eberswalde
country: Germany
facility: Klinikum Barnim GmbH, Werner Forssmann Krankenhaus
city: Ellwangen
country: Germany
facility: Virngrund-Klinik Ellwangen
city: Emden
country: Germany
facility: Hans - Susemihl - Krankenhaus
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Erlangen
country: Germany
facility: Medizinische Klinik III - Universitaetsklinikum Erlangen
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: Flensburg
country: Germany
facility: Schwerpunktpraxis fuer Haematologie und Onkologie - Flensburg
city: Frankenthal
country: Germany
facility: Gemeinschaftspraxis fuer Internistische - Frankenthal
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Frankfurt am Main
country: Germany
facility: St. Marienkrankenhaus - Frankfurt am Main
city: Frankfurt
country: Germany
facility: Onkologie Bethanien
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Frechen
country: Germany
facility: Praxis Internistischer Onkologie und Haematologie - Frechen
city: Freiburg
country: Germany
facility: Gemeinschaftspraxis - Freiburg
city: Freiburg
country: Germany
facility: Evang. Deaconess Hospital Freiburg
city: Freiburg
country: Germany
facility: Praxis fur Interdisziplinaere Onkologie
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Fulda
country: Germany
facility: Municipal Hospital Complex
city: Garmisch-Partenkirchen
country: Germany
facility: Klinikum Garmisch - Partenkirchen GmbH
city: Gehrden
country: Germany
facility: Robert - Koch Hospital
city: Gelsenkirchen
country: Germany
facility: Saint Josef Hospital
city: Germering
country: Germany
facility: Internistische Praxisgemeinschaft
city: Giessen
country: Germany
facility: Centre for Internal Medicine Giessen
city: Giessen
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
city: Goch
country: Germany
facility: Wilhelm-Anton-Hospital gGmbH, Goch
city: Goslar
country: Germany
facility: DR Herbert - Nieper Krankenhaus Goslar
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Gummersbach
country: Germany
facility: Kreiskrankenhaus Gummersbach GMBH
city: Gustrow
country: Germany
facility: Internistisch-Haematologische Gemeinschaftspraxis - Gustrow
city: Görlitz
country: Germany
facility: Staedtisches Klinikum Görlitz GmbH
city: Göttingen
country: Germany
facility: Universitaetsklinikum Göttingen
city: Gütersloh
country: Germany
facility: Staedtisches Klinikum Gütersloh
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Hagen
country: Germany
facility: St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
city: Halberstadt
country: Germany
facility: St. Salvator Krankenhaus
city: Halle
country: Germany
facility: Internistische Gemeinschaftspraxis - Halle
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Halle
country: Germany
facility: Krankenhaus St. Elisabeth und St. Barbara
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH
city: Haltern
country: Germany
facility: St. Sixtus Hospital
city: Hamburg
country: Germany
facility: Praxis fuer Innere Medizin - Bergedorf
city: Hamburg
country: Germany
facility: Marienkrankenhaus
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus Altona
city: Hamburg
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. med. Verpoort, PD Dr. med. Zeller and Dr. med. Wierecky
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Nord Heidberg
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Altona
city: Hamm
country: Germany
facility: St. Marien Hospital
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hanau
country: Germany
facility: Klinikum Stadt Hanau
city: Hannover
country: Germany
facility: Schwerpunktpraxis Haematologie/Onkologie - Hannover
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Hannover
country: Germany
facility: Henriettenstiftung Frauenklinik
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Harrislee
country: Germany
facility: Oncology Specialists Clinic
city: Heidelberg
country: Germany
facility: Ruprecht - Karls - Universitaet Heidelberg
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
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: Hildesheim
country: Germany
facility: St. Bernward Krankenhaus
city: Hildesheim
country: Germany
facility: Staedtisches Krankenhaus Hildesheim
city: Holzminden
country: Germany
facility: Evang. Hospital
city: Homberg
country: Germany
facility: Haematologie und Internistische Onkologie Praxis
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Hoyerswerda
country: Germany
facility: Hospital Complex Hoyerswerda
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Jena
country: Germany
facility: Internistische Gemeinschaftspraxis - Jena
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller Universitaet Jena
city: Kaiserslautern
country: Germany
facility: Onkologische Gemeinschaftspraxis - Kaiserslautern
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Karlsruhe
country: Germany
facility: St. Vincentius - Kliniken
city: Kassel
country: Germany
facility: Red Cross Hospital Kassel
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kempten
country: Germany
facility: Klinikum Kempten Oberallgaeu
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel
city: Koblenz
country: Germany
facility: Praxis fuer Haematologie und Onkologie
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH
city: Kornwestheim
country: Germany
facility: Leonardis Clinic
city: Krefeld
country: Germany
facility: Haematologische / Onkologische Schwerpunktpraxis
city: Krefeld
country: Germany
facility: Klinikum Krefeld GmbH
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Kronach
country: Germany
facility: Frankenwald Klinik
city: Landshut
country: Germany
facility: Internistische Praxis - Landshut
city: Landshut
country: Germany
facility: Klinikum Landshut
city: Lebach
country: Germany
facility: Caritas - Krakenhaus Lebach
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Leipzig
country: Germany
facility: Praxis fuer Onkologie am Diakonissenhaus
city: Leipzig
country: Germany
facility: Forschungsgesellschaft mbH
city: Leipzig
country: Germany
facility: Gemeinschaftspraxis fuer Dres. Aldaoud und Schwarzer
city: Leipzig
country: Germany
facility: University Leipzig Clinic of Internal Medicine
city: Leipzig
country: Germany
facility: Klinikum "St. Georg" Leipzig
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: Loerrach
country: Germany
facility: Kreiskrankenhaus Loerrach
city: Loerrach
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Ludwigshafen am Rhein
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein
city: Ludwigshafen
country: Germany
facility: St. Marien Hospital Ludwighafen
city: Luebeck
country: Germany
facility: Schwerpunktpraxis fuer Haematologie und Onkologie - Luebeck
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
city: Luebeck
country: Germany
facility: Sana Kliniken Luebeck
city: Luedenscheid
country: Germany
facility: Kreiskrankenhaus Luedenscheid
city: Magdeburg
country: Germany
facility: Universitatsklinikum der MA
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg - Altstadt
city: Magdeburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Magdeburg
city: Mainz
country: Germany
facility: St. Vincenz und Elisabeth Hospital
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Mannheim
country: Germany
facility: Gemeinschaftspraxis
city: Mannheim
country: Germany
facility: III Medizinische Klinik Mannheim
city: Marburg
country: Germany
facility: Schwerpunktpraxis Internist Onkologie - Marburg
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH - Marburg
city: Mayen
country: Germany
facility: Regional Hospital Mayen
city: Memmingen
country: Germany
facility: Gemeinschaftspraxis Dres. med. Ellbrueck/Goeller/Kraenzle/Niedermeier/Jocham
city: Meppen
country: Germany
facility: Krankenhaus Ludmillenstift
city: Minden
country: Germany
facility: Gemeinschaftspraxis - Minden
city: Minden
country: Germany
facility: Klinikum Minden
city: Moenchengladbach
country: Germany
facility: Krankenhaus Maria Hilf GmbH
city: Moenchengladbach
country: Germany
facility: Haematologische Praxis - Moenchengladbach
city: Monchengladbach
country: Germany
facility: Ev. Hospital Bethesda
city: Muelheim an der Ruhr
country: Germany
facility: Evangelisches Krankenhaus - Muelheim
city: Muelheim An Der Ruhr
country: Germany
facility: St. Marien Hospital - Muelheim an der Ruhr
city: Muenster
country: Germany
facility: Gemeinschaftspraxis - Muenster
city: Muenster
country: Germany
facility: Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
city: Muenster
country: Germany
facility: Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster
city: Munich
country: Germany
facility: Universitaets - Kinderpoliklinik
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Munich Oncologic Practice at Elisenhof
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: Municipal Hospital Munich
city: Mutlangen
country: Germany
facility: Klinikum Schwaebisch Gmuend Stauferklinik
city: Münchberg
country: Germany
facility: Kreiskrankenhaus Muenchberg
city: Nettetal
country: Germany
facility: Staedtisches Krankenhaus Nettetal GmbH
city: Neubrandenburg
country: Germany
facility: Klinikum Neubrandenburg
city: Neumarkt
country: Germany
facility: Onkologische Schwerwpunktpraxis Dr. Ladda
city: Neumarkt
country: Germany
facility: Regional Hospital Neumarkt
city: Neunkirchen
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Schmidt
city: Neunkirchen
country: Germany
facility: Staedtisches Klinikum Neunkirchen gGmbH
city: Neuss
country: Germany
facility: Internistische Praxis - Neuss
city: Neuss
country: Germany
facility: Lukaskrankenhaus Neuss
city: Neuwied
country: Germany
facility: DRK Krankenhaus Neuwied
city: Norderstedt
country: Germany
facility: Praxis fuer Haematologie und Interne Onkologie
city: Nordhorn
country: Germany
facility: Gemeinschaftspraxis fuer Onkologie - Nordhorn
city: Northeim
country: Germany
facility: Gemeinschaftspraxis fuer Haematologie - Northeim
city: Nuremberg
country: Germany
facility: Praxisklinik fuer Innere Medizin - Nuernberg
city: Nuremberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Oberstaufen
country: Germany
facility: Schlossbergkliniken Oberstaufen
city: Offenbach
country: Germany
facility: Internistische Gemeinschaftspraxis - Offenbach
city: Offenburg
country: Germany
facility: Klinikum Offenburg
city: Oldenburg
country: Germany
facility: Pius Hospital - Oldenburg
city: Oldenburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Oldenburg
city: Oldenburg
country: Germany
facility: Ev. Hospital Oldenburg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Olpe
country: Germany
facility: St. Martinus Hospital - Olpe
city: Osnabrück
country: Germany
facility: Marien Hospital
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück GmbH
city: Osnabrück
country: Germany
facility: Paracelsus - Klinik Osnabrück
city: Paderborn
country: Germany
facility: Bruederkrankenhaus St. Josef Paderborn
city: Parchim
country: Germany
facility: Asklepios Klinik - Parchim
city: Pforzheim
country: Germany
facility: Staedtisches Krankenhaus
city: Pforzheim
country: Germany
facility: Krankenhaus Siloah - Pforzheim
city: Pforzheim
country: Germany
facility: Praxis fuer Innere Medizin am Krankenhaus Siloah - Pforzheim
city: Pinneberg
country: Germany
facility: Gemeinschaftspraxis - Pinneberg
city: Potsdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Radebeul
country: Germany
facility: Kreiskrankenhaus Radebeul
city: Ravensburg
country: Germany
facility: Gemeinschaftspraxis - Ravensburg
city: Ravensburg
country: Germany
facility: Krankenhaus St. Elisabeth - Ravensburg
city: Recklinghausen
country: Germany
facility: Elisabeth Krankenhaus
city: Recklinghausen
country: Germany
facility: Prosper-Hospital Recklinghausen
city: Regensburg
country: Germany
facility: Hematologische Onkologische Praxis
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Rehling
country: Germany
facility: Internistische Praxis Dres. Hempel und Hochdorfer
city: Remscheid
country: Germany
facility: Klinikum Remscheid GmbH
city: Rheine
country: Germany
facility: Jakobi Krankenhaus
city: Rostock
country: Germany
facility: Haematologische/Onkologische Schwerpunktpraxis - Rostock
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Rostock
country: Germany
facility: Klinikum Suedstadt Rostock
city: Rotenburg
country: Germany
facility: Diakonie - Krankenhaus
city: Russelsheim
country: Germany
facility: Internistische Schwerpunktpraxis
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresia
city: Saarbruecken
country: Germany
facility: Gemeinschaftspraxis - Saarbruecken
city: Saarlouis
country: Germany
facility: St. Elizabeth-Klinik Saarlouis
city: Schleswig
country: Germany
facility: Martin - Luther Hospital
city: Schmiedeberg
country: Germany
facility: Praxis fur Innere Medizin - Schmiedeberg
city: Schwabisch Hall
country: Germany
facility: Deaconess Hospital
city: Schweinfurt
country: Germany
facility: Gemeinschaftspraxis fuer Haematologie und Internist - Schweinfurt
city: Schweinfurt
country: Germany
facility: Leopoldina - Krankenhaus
city: Schwelm
country: Germany
facility: HELIOS Klinikum - Schwelm
city: Schwerin
country: Germany
facility: Klinikum Schwerin
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Siegen
country: Germany
facility: Evang. Jung-Stilling Hospital
city: Solingen
country: Germany
facility: St. Lukas - Clinic Solingen
city: Stadtlohn
country: Germany
facility: Krankenhaus Maria-Hilf - Stadtlohn
city: Straubing
country: Germany
facility: Onkologische Schwerpunktpraxis - Straubing
city: Stuttgart
country: Germany
facility: Hospital Bad Cannstatt
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: Gastroenterologische und Haematologisch-Onkologische Praxis E. M. Dr. Hoering von Ehr Respondek
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart - Buergerhospital
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: Onkologische Gemeinschaftspraxis - Trier
city: Trier
country: Germany
facility: Krankenanstalt Mutterhaus der Borromaerinnen
city: Trier
country: Germany
facility: Krankenhaus Der Barmherzigen Brueder
city: Troisdorf
country: Germany
facility: Praxis Fuer Internistische Haematologie / Onkologie
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Tutzing
country: Germany
facility: Hospital Tutzing
city: Twistringen
country: Germany
facility: Praxis fuer Haematologie und Onkologie
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: Villingen
country: Germany
facility: Onkologische Schwerpunktpraxis - Villingen
city: Waldbrol
country: Germany
facility: Regional Hospital Waldbrol
city: Weiden
country: Germany
facility: Haematologische Praxis
city: Weilheim
country: Germany
facility: Gemeinschaftspraxis feur Haemotologie und Onkologie - Weilheim
city: Weimar
country: Germany
facility: Sophien - und Hufeland - Klinikum Weimar gGmbH
city: Wendlingen
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Wernigerode
country: Germany
facility: Harz-Klinikum Wernigerode-Blankenburg GmbH
city: Westerland
country: Germany
facility: Asklepios Nordseeklinik Westerland GmbH
city: Westerstede
country: Germany
facility: Ammerland-Klinik GmbH
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: Wittenberg
country: Germany
facility: Evangelisches Krankenhaus - Lutherstadt Wittenberg
city: Witten
country: Germany
facility: Ev. Hospital Witten-Herdecke
city: Wolfsburg
country: Germany
facility: Klinikum der Stadt Wolfsburg
city: Worms
country: Germany
facility: Burkhard and Reimann Gemeinschaftspraxis
city: Wuerzburg
country: Germany
facility: Medizinische Poliklinik, Universitaet Wuerzburg
city: Wuppertal 2
country: Germany
facility: Kliniken St. Antonius
city: Wuppertal
country: Germany
facility: Helios Kliniken Wuppertal University Hospital
city: Zwickau
country: Germany
facility: Heinrich-Braun-Krankenhaus Zwickau
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Children's Hospital
city: Wroclaw
country: Poland
facility: Akademia Medyczna im. Piastow Slaskich
city: Goeteborg
country: Sweden
facility: Goeteborg University
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: Universitaets-Kinderspital beider Basel
city: Locarno
country: Switzerland
facility: Ospedale "la Carita", Locarno
city: Lucerne 16
country: Switzerland
facility: Kinderspital Luzern
city: St. Gallen
country: Switzerland
facility: Ostschweizer Kinderspital
city: Zurich
country: Switzerland
facility: University Children's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
Study officials:
affiliation: Universitaetsklinikum des Saarlandes
name: Michael G.M. Pfreundschuh, MD
role: STUDY_CHAIR
affiliation: Asklepios Klinik St. Georg
name: Norbert Schmitz, MD, PhD
role: STUDY_CHAIR
References: