ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT02858258
- Lead Sponsor
- Prof. Dr. M. Dreyling (co-chairman)
- Brief Summary
The primary objective of the the trial is to establish one of three study arms, as future standard based on the comparison of the investigator-assessed failure-free survival.
- Detailed Description
Objectives and Endpoints
Primary Objective:
To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance experimental arm I) as future standard based on the comparison of the investigator-assessed failure-free survival (FFS).
Secondary Objectives:
* To compare the efficacy of the three treatment arms in terms of secondary efficacy endpoints
* To determine the safety and tolerability of ibrutinib during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints
Primary Endpoint:
FFS defined as time from start of treatment to stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause.
Secondary Efficacy Endpoints:
* Overall survival (OS)
* Progression-free survival (PFS) from randomization, from end of induction immuno-chemotherapy in patients with CR or PR at end of induction immuno-chemotherapy, and from the staging 6 weeks after end of induction assessment (at month 6)
* Overall response and complete remission rates at midterm, at end of induction, 3 months after end of induction immunochemotherapy (at month 6)
* PR to CR conversion rate during follow-up after end of induction immuno-chemotherapy
Secondary Toxicity Endpoints:
* Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during induction immuno-chemotherapy and during periods of follow-up after response to immune-chemotherapy
* Cumulative incidence rates of SPMs
Exploratory Objectives:
* To compare feasibility of ASCT in arm A+I vs. arm A
* To compare minimal residual disease status between the three treatment groups
* To determine the impact of ibrutinib during induction immuno-chemotherapy and during maintenance therapy on the minimal residual disease status
* To determine the prognostic value of minimal residual disease status
* To determine the prognostic value of positron emission tomography with fluorine 18-fluorodeoxyglucose
* To determine clinical and biological prognostic and predictive factors
* To determine the role of total body irradiation (TBI) in ASCT conditioning
Exploratory Endpoints:
* Rate of successful stem cell mobilisations (success: separation of at least 2x2x10(6) CD34-positive cells, including a back-up)
* Rate of molecular remissions (MRD-negative patients) at midterm, at end of induction immuno-chemotherapy, and at staging time-points during follow-up in patients with remission after end of induction immuno-chemotherapy
* Time to molecular remission from start of therapy
* Time to molecular relapse for patients in clinical and molecular remission after end of induction immunochemotherapy
* RD in FDG-PET negative or positive patients after induction and ASCT
Exploratory objectives may be evaluated only in a subset of patients according to local standards and resources.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 870
All patients must meet the following criteria:
-
Histologically confirmed diagnosis of MCL according to WHO classification
-
suitable for high-dose treatment including high-dose Ara-C
-
Stage II-IV (Ann Arbor)
-
Age ≥ 18 years and ≤ 65 years
-
Previously untreated MCL
-
At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
-
ECOG/WHO performance status ≤ 2
-
The following laboratory values at screening (unless related to MCL):
- Absolute neutrophil count (ANC) ≥1000 cells/µL
- Platelets ≥100,000 cells/µL
- Transaminases (AST and ALT) ≤3 x upper limit of normal (ULN)
- Total bilirubin ≤2 x ULN unless due to known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome])
- Creatinine ≤2 mg/dL or calculated creatinine clearance ≥ 50 mL/min
-
Written informed consent form according to ICH/EU GCP and national regulations
-
Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug.
Any potential subject who meets any of the following criteria will be excluded from participating in the study.
-
Major surgery within 4 weeks prior to randomization.
-
Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg phenprocoumon).
-
History of stroke or intracranial hemorrhage within 6 months prior to randomization.
-
Requires treatment with strong CYP3A4/5 inhibitors.
-
Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
-
Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.
-
Known CNS involvement of MCL
-
Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of ibrutinib itself or to the excipients in its formulation)
-
Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
-
Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon except prephase therapy according to trial protocol
-
Serious concomitant disease interfering with a regular therapy according to the study protocol:
- Cardiac (Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below LLN )
- Pulmonary (e.g. chronic lung disease with hypoxemia)
- Endocrinological (e.g. severe, not sufficiently controlled diabetes mellitus)
- Renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value and/or creatinin clearance < 50 ml/min)
- Impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2,0 mg/dl unless due to morbus Meulengracht (Gilbert-Meulengracht-Syndrome)
-
Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test)
-
Prior organ, bone marrow or peripheral blood stem cell transplantation
-
Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer or in situ uterine cervix cancer
-
Pregnancy or lactation
-
Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
-
Subjects not able to give consent
-
Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial
-
Participation in another clinical trial within 30 days before randomization in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Arm A+I ASCT conditioning R-CHOP+Ibrutinib/R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days 1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenace) Standard Arm A ASCT conditioning R-CHOP/R-DHAP: Alternating 3 cycles of R-CHOP in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM Experimental Arm A+I Ibrutinib (Induction) R-CHOP+Ibrutinib/R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days 1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenace) Standard Arm A R-CHOP/R-DHAP R-CHOP/R-DHAP: Alternating 3 cycles of R-CHOP in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM Experimental Arm A+I R-CHOP/R-DHAP R-CHOP+Ibrutinib/R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days 1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenace) Experimental Arm I R-CHOP/R-DHAP R-CHOP+Ibrutinib / R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenance) Experimental Arm I Ibrutinib (Induction) R-CHOP+Ibrutinib / R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenance) Experimental Arm I Ibrutinib (Maintenance) R-CHOP+Ibrutinib / R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenance) Experimental Arm A+I Ibrutinib (Maintenance) R-CHOP+Ibrutinib/R-DHAP: Alternating 3 cycles of R-CHOP + Ibrutinib at Days 1-19 in cycle 1,3,5 and 3 cyles of R-DHAP in cycle 2,4,6; each 21 day cycle Drug: R-CHOP/R-DHAP Drug: Ibrutinib (Induction) ASCT conditioning (ASCT: autologous stemm cell transplantation) Drug: THAM or BEAM 2 years Ibrutinib Maintenance Drug: Ibrutinib (Maintenace)
- Primary Outcome Measures
Name Time Method Failure Free Survival From start of treatment until stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause, whichever comes first, assessed up to 120 months.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) PFS is the time to progression or death from any cause. Assed up to 120 months. Number of Adverse Events by CTC grade (Version 4.03) From start of treatment through the study conduction, up to 120 months. Toxicity Endpoints
Number of participants with treatment-related adverse events as assessed by CTC Version 4.03 From start of Ibrutinib treatment during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints. Through study conduction, an average of up to 30 months. Safety and tolerability
Overall Survival From start of treatment until the date of first documented progression, assessed up to 120 months. Number of Secondary Primary Malignancies From start of treatment through the study conduction, up to 120 months. Toxicity Endpoints
Trial Locations
- Locations (112)
DONAUISAR Klinikum Deggendorf, Innere Medizin II
🇩🇪Deggendorf, Germany
Knappschaftskrankenhaus Bochum-Langendreer
🇩🇪Bochum, Germany
Charité Univ.-Medizin Berlin, Med. Klinik - Hämatologie, Onkologie und Tumorimmunologie
🇩🇪Berlin, Germany
Klinikum Chemnitz gGmbH, Klinik f. Innere Medizin II
🇩🇪Chemnitz, Germany
Zentralklinik Augsburg, II. Med. Klinik, Hämatologie int. Onkologie
🇩🇪Augsburg, Germany
Herlev Hospital, Department of Hematology L121
🇩🇰Herlev, Denmark
Sjaelland University Hospital, Dept of Hematology
🇩🇰Roskilde, Denmark
Onkologische Gemeinschaftspraxis Dr. Janssen/Dr. Reichert in der Ubbo-Emmius-Klinik
🇩🇪Aurich, Germany
Klinikum Bayreuth, Klinik f. Onkologie und Hämatologie
🇩🇪Bayreuth, Germany
Vivantes Klinikum Am Urban, Klinik f. Innere Medizin, Hämatologie und Onkologie
🇩🇪Berlin, Germany
Diako ev. Diakonie-KH gGmbH, Med. Klinik II, Hämatologie und Onkologie
🇩🇪Bremen, Germany
St.-Johannes-Hospital
🇩🇪Dortmund, Germany
Uniklinik Köln, Klinik I für Innere Medizin
🇩🇪Köln, Germany
Asklepios Klinik Altona, II. Med.Abt. f. Hämatologie und internistische Onkologie, Stammzelltransplantation
🇩🇪Hamburg, Germany
Klinikum Idar-Oberstein GmbH, Medizinische Klinik I
🇩🇪Idar-Oberstein, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik f. Innere Medizin II - Hämatologie und Onkologie
🇩🇪Kiel, Germany
AOU Policlinico Careggi, Unità Funzionale di Ematologia
🇮🇹Firenze, Italy
Universitätsmedizin Rostock, Abt. f. Hämatologie und Onkologie, Klinik und Poliklinik für Innere Medizin
🇩🇪Rostock, Germany
Onkologisch-Hämatologische Praxis Dr. Vehling-Kaiser
🇩🇪Landshut, Germany
Klinikum Lippe GmbH, Onkologie und Hämatologie
🇩🇪Lemgo, Germany
Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Med. Klinik A
🇩🇪Ludwigshafen, Germany
Johannes Wiesling Klinikum Minden, Klinik f. Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin
🇩🇪Minden, Germany
Klinikum Nürnberg,5. Medizinische Klinik, Onkologie / Hämatologie
🇩🇪Nürnberg, Germany
KH Barmherzige Brüder, Klinik f. Onkologie und Hämatologie
🇩🇪Regensburg, Germany
Klinikum Traunstein, Hämatologie - Onkologie- Palliativmedizin
🇩🇪Traunstein, Germany
Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo, SC Ematologia
🇮🇹Alessandria, Italy
Policlinico S. Orsola Malpighi, Istituto di Ematologia e Oncologia Medica Seragnoli
🇮🇹Bologna, Italy
Spedali Civili, Struttura Complessa di Ematologia
🇮🇹Brescia, Italy
Ospedale Businco, UO Ematologia - CTMO
🇮🇹Cagliari, Italy
ASO S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo
🇮🇹Cuneo, Italy
IRCCS AOU S. Martino - IST, Clinica Ematologia
🇮🇹Genova, Italy
Ospedale Niguarda, Struttura Complessa di Ematologia
🇮🇹Milano, Italy
Università di Modena e Reggio Emilia Policlinico - COM Centro Oncologico Modenese, Dipartimento di Oncologia ed Ematologia
🇮🇹Modena, Italy
Ospedale S. Maria delle Croci, U.O di Ematologia
🇮🇹Ravenna, Italy
Policlinico Tor Vergata, UOC Oncoematologia
🇮🇹Roma, Italy
Ospedale degli Infermi, U.O. Ematologia
🇮🇹Rimini, Italy
Casa Sollievo della Sofferenza, U.O. Ematologia
🇮🇹San Giovanni Rotondo, Italy
A.O. Città della Salute e della Scienza, SC Ematologia
🇮🇹Torino, Italy
Ospedale Cà Foncello, U.O.C. Ematologia
🇮🇹Treviso, Italy
Ospedale Cardinale Panico, Divisione di Ematologia
🇮🇹Tricase, Italy
Ospedale S. Bortolo, Ematologia
🇮🇹Vicenza, Italy
Aalborg University Hospital, Dept of Hematology
🇩🇰Aalborg, Denmark
Aarhus University Hospital, Dept of Hematology
🇩🇰Aarhus C, Denmark
Odense University Hospital, Dept of Hematology X
🇩🇰Odense C, Denmark
Universitätsklinikum Erlangen, Med. Klinik 5, Hämatologie und internistische Onkologie
🇩🇪Erlangen, Germany
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
🇩🇪Dresden, Germany
Universitätsklinikum Heidelberg, Med. Klinik - Innere Medizin V - Hämatologie, Onkologie und Rheumatologie
🇩🇪Heidelberg, Germany
Helios Klinikum Erfurt GmbH, Zentrum f. Innere Medizin u. internistische Onkologie, Hämostaseologie
🇩🇪Erfurt, Germany
Universitätsmedizin Greifswald, Klinik u. Poliklinik f. Innere Medizin C, Hämatologie u. Onkologie-, Transplantationszentrum
🇩🇪Greifswald, Germany
Universitätsklinikum Hamburg-Eppendorf (UKE), II. Med. Klinik u. Poliklinik, Onkologie, Hämatologie, KMT
🇩🇪Hamburg, Germany
Katholisches Krankenhaus Hagen gGmbH, St.-Marien-Hospital, Klinik f. Hämatologie und Onkologie
🇩🇪Hagen, Germany
Universitätsklinikum des Saarlandes, Klinik f. Innere Medizin I Hämatologie & Onkologie
🇩🇪Homburg, Germany
Klinikum Oldenburg gGmbH, Med. Klinik II
🇩🇪Oldenburg, Germany
Universitätsklinikum Tübingen, Med Klinik I, Innere Medizin II
🇩🇪Tübingen, Germany
Universitätsklinikum Würzburg, Med. Klinik u. Poliklinik II /ZIM
🇩🇪Würzburg, Germany
Comprensorio Sanitario di Bolzano, Ematologia e trapianto di midollo osseo
🇮🇹Bolzano, Italy
IRCCS AOU S. Martino - IST, Ematologia
🇮🇹Genova, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Ematologia
🇮🇹Meldola (FC), Italy
Istituto Scientifico San Raffaele, Unità Ricerca Clinica Linfomi
🇮🇹Milano, Italy
Ospedale S. Gerardo, Divisione di Ematologia
🇮🇹Monza, Italy
"IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale", Ematologia Oncologica
🇮🇹Napoli, Italy
AOU Maggiore della Carità - Università del Piemonte Orientale, S.C.D.U Ematologia
🇮🇹Novara, Italy
AO Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
🇮🇹Palermo, Italy
IRCCS Fondazione Policlinico San Matteo, Clinica Ematologia
🇮🇹Pavia, Italy
Azienda Ospedaliera Pisana Ospedale "S.Chiara", Dipartimento di Oncologia Divisione di Ematologia
🇮🇹Pisa, Italy
Azienda Ospedaliera Bianchi, Melacrino, Morelli, Divisione di Ematologia
🇮🇹Reggio Calabria, Italy
Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Ematologia
🇮🇹Reggio Emilia, Italy
Università La Sapienza, Ematologia
🇮🇹Roma, Italy
A.O. U. Città della Salute e della Scienza, S C Ematologia U
🇮🇹Torino, Italy
ASUI Integrata di Udine, Clinica Ematologia
🇮🇹Udine, Italy
Ospedale Policlinico G.B. Rossi, "Centro trapianto midollo osseo Ematologia"
🇮🇹Verona, Italy
Stavanger University Hospital, Division for Hematology&Oncology
🇳🇴Stavanger, Norway
Oslo University Hospital, Dept of Oncology
🇳🇴Oslo, Norway
St. Olavs Hospital, Department of Oncology
🇳🇴Trondheim, Norway
University Hospital, Dept of Hematolgy
🇸🇪Linköping, Sweden
Sunderbyn Hospital, Dept of Medicine
🇸🇪Lulea, Sweden
Norrland University Hospital, Dept of Oncology
🇸🇪Umea, Sweden
Academic Hospital, Dept of Oncology
🇸🇪Uppsala, Sweden
Örebro University Hospital, Dept of Oncology
🇸🇪Örebro, Sweden
Sahlgrenska University Hospital, Section of Hematology and Coagulation, Dept of internal medicine
🇸🇪Göteborg, Sweden
Skane University Hospital
🇸🇪Lund, Sweden
Karolinska University Hospital, Center of Hematology
🇸🇪Stockholm, Sweden
UNN Tromsø, Oncology Dep
🇳🇴Tromsø, Norway
Haukeland University Hospital , Dept. of Oncology and Medical Physics
🇳🇴Bergen, Norway
Helios Klinikum Berlin-Buch, Hämatologie, Onkologie und Tumorimmunologie
🇩🇪Berlin, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Gemeinschaftspraxis Dr. Mohm und Prange-Krex - Fachärzte für Innere Medizin und Hämatologie und Onkologie
🇩🇪Dresden, Germany
Universitätsklinikum Düsseldorf, Klinik f. Hämatologie, Onkologie und klinische Immunologie
🇩🇪Düsseldorf, Germany
Marien Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Essen, Klinik f. Hämatologie
🇩🇪Essen, Germany
Klinikum Landshut gGmbH, Med. Klinik III, Hämatologie/Internistische Onkologie
🇩🇪Landshut, Germany
Universitätsklinikum Magdeburg AöR, Klinik f. Hämatologie und Onkologie
🇩🇪Magdeburg, Germany
Universitätsklinikum Freiburg, Klinik f. Innere Medizin, Hämatologie, Onkologie u. Stammzelltransplantation
🇩🇪Freiburg, Germany
Caritas-KHLebach, Gemeinschaftspraxis f. Hämatologie und Onkologie, Onkologisches Zentrum Lebach
🇩🇪Lebach, Germany
Universitätsklinikum Leipzig AöR, selbständige Abteilung f. Hämatologie und Internistische Onkologie, Hämostaseologische Ambulanz
🇩🇪Leipzig, Germany
Klinikum der Universität München, Med. Klinik und Poliklinik III
🇩🇪München, Germany
Universitätsmedizin Göttingen, Zentrum f. Innere Medizin, Klinik f. Hämatologie und Medizinische Onkologie
🇩🇪Göttingen, Germany
Universitätsmedizin Jena, Klinik f. Innere Medizin II, Abteilung Hämatologie u. Internistische Onkologie
🇩🇪Jena, Germany
Gemeinschaftsklinikum Mittelrhein gGmbH, Ev. Stift St. Martin, Klinik f. Innere Medizin
🇩🇪Koblenz, Germany
Klinikum Rechts der Isar, III. Med. Klinik - Hämatologie und Onkologie
🇩🇪München, Germany
Universitätsklinikum Münster, Med. Klinik A, Translationale Onkologie / Lymphome
🇩🇪Münster, Germany
Klinikum Ernst von Bergmann Potsdam gGmbH, Zentrum f. Innere Medizin, Klinik f. Hämatologie und Onkologie
🇩🇪Potsdam, Germany
Robert-Bosch-Krankenhaus, Abt.f. Hämatologie und Onkologie
🇩🇪Stuttgart, Germany
Klinikum Stuttgart - Katharinenhospital, Klinik f. Hämatologie und Onkologie
🇩🇪Stuttgart, Germany
Universitätsklinikum Ulm, Klinik für Innere Medizin III
🇩🇪Ulm, Germany
Klinikum Mutterhaus der Borromäerinnen gGmbH, Okologisches Zentrum
🇩🇪Trier, Germany
Klinikum Wolfsburg, Med. Klinik II
🇩🇪Wolfsburg, Germany
Rigshospitalet, Clinic of Hematology
🇩🇰Copenhagen, Denmark
Universitätsmedizin der Univ. Mainz, III. Med. Klinik u. Poliklinik
🇩🇪Mainz, Germany
St.-Antonius-Hospital Eschweiler, Klinik für Hämatologie und Onkologie
🇩🇪Eschweiler, Germany
Städtisches Klinikum Karlsruhe, Med. Klinik III, Hämatologie und Onkologie
🇩🇪Karlsruhe, Germany
Praxisklinik f. Hämatologie und Onkologie Koblenz
🇩🇪Koblenz, Germany