Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia
- Conditions
- Leukemia
- Interventions
- Radiation: radiation therapy
- Registration Number
- NCT00430118
- Lead Sponsor
- University Hospital Schleswig-Holstein
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia.
PURPOSE: Thisphase III trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with acute lymphoblastic leukemia.
- Detailed Description
OBJECTIVES:
* Compare the relative efficacy of induction therapy comprising dexamethasone or prednisone, in terms of a higher rate of event-free survival (EFS) and overall survival and a reduced rate of relapse, in pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia (ALL).
* Compare the relative safety of a reduced-intensity reintensification regimen comprising dexamethasone, vincristine, cyclophosphamide, and anthracyclines vs a standard treatment regimen in pediatric patients with standard-risk ALL identified by fast clearance of leukemic cells.
* Compare the efficacy of a second delayed reintensification regimen vs standard reintensification therapy, in terms of improved EFS, in pediatric patients with intermediate-risk ALL.
* Compare the efficacy of extended reintensification therapy (triple reinduction) vs standard reintensification therapy (intensive pulses and one reintensification) in pediatric patients with high-risk ALL.
OUTLINE: This is a randomized, multicenter study.
* Prednisone prephase therapy: Patients receive oral prednisone on days 1-7 and one dose of methotrexate (MTX) intrathecally (IT) on day 1.
* Induction/consolidation therapy, protocol I: Patients are randomized to 1 of 2 treatment arms.
* Arm I (closed to accrual as of 6/30/2006): Patients receive prednisone (PRED) on days 8-28.
* Arm II (closed to accrual as of 6/30/2006): Patients receive dexamethasone (DEXA) on days 8-28.
Patients in both arms also receive vincristine (VCR) and daunorubicin hydrochloride (DNR) once weekly in weeks 2-5; asparaginase (ASP) on days 12-33; cyclophosphamide (CPM) on days 36 and 64; cytarabine (ARA-C) in weeks 6-9; mercaptopurine (MP) on days 36-63; and MTX IT on days 1, 12, 33, 45, and 59.\*
NOTE: \*Patients with CNS disease also receive MTX IT on days 18 and 27.
After completion of induction/consolidation therapy, patients are stratified according to risk group based on disease response (standard-risk \[SR\] group \[negative minimal residual disease (MRD) on day 33 and before protocol M, day 78\] vs high-risk \[HR\] group \[MRD ≥ 10\^-³ on day 78\] vs intermediate-risk \[IR\] group \[all nonSR/nonHR\]).\* Patients with SR and IR disease proceed to extracompartment therapy. Patients with HR disease proceed to reintensification therapy.
NOTE: \*Patients meeting any of the following criteria are placed in the HR group regardless of MRD response: Philadelphia chromosome-positive disease (BCR/ABL or t\[9;22\]; translocations \[t4;11\]\[q11;q23\] or MLL/AF4); "prednisone-poor-response" (≥ 1,000 blasts/mm³ in the peripheral blood on day 8 after prednisone prephase therapy); or no response to study induction therapy (M2/3 at day 33).
* Extracompartment therapy, protocol M: Patients receive MP on days 1-56 and MTX on days 8, 22, 36, and 50.
After completion of extracompartment therapy, SR and IR patients proceed to reintensification therapy. SR patients are randomized to arms I or II. IR patients are randomized to arms I or III. HR patients who have completed induction/consolidation therapy are randomized to arms IV or V.
* Reintensification therapy:
* Arm I (standard reinduction therapy, protocol II \[closed to accrual as of 6/30/2006\]): SR and IR patients receive DEXA on days 1-22; VCR and doxorubicin hydrochloride (DOX) in weeks 2-5; ASP on days 8, 11, 15, and 18; CPM on day 36; ARA-C and thioguanine (TG) on days 36-49; and MTX IT on days 38 and 45.\* Patients then proceed to maintenance therapy.
NOTE: \*Patients with CNS disease also receive MTX IT on days 1 and 18.
* Arm II (reduced-intensity reinduction therapy, protocol III \[closed to accrual as of 6/30/2006\]): SR patients receive DEXA on days 1-15; VCR and DOX on days 1 and 8; ASP on days 1, 4, 8, and 11; CPM on day 15; ARA-C and TG on days 15-28; and MTX IT on days 17 and 24.\* Patients then proceed to maintenance therapy.
NOTE: \*Patients with CNS disease also receive MTX on day 1.
* Arm III (reduced-intensity reinduction/second delayed reinduction therapy \[double reintensification therapy\] \[closed to accrual as of 6/30/2006\]): IR patients receive reduced-intensity reintensification therapy as in arm II. After a 10-week interim maintenance phase, treatment repeats once for a second delayed course of reintensification therapy. Patients then proceed to maintenance therapy.
* Arm IV (standard reintensification therapy \[closed to accrual as of 6/30/2006\]): HR patients receive two sequences of the following HR therapy elements (i.e., in this order: 1, 2, 3, 1, 2, 3) following reintensification therapy as in arm I. Patients then proceed to maintenance therapy.
* Element HR-1: Patients receive DEXA on days 1-5; VCR on days 1 and 6; ARA-C twice on day 5; MTX and CPM every 12 hours on days 2-4 (5 doses); ASP on days 6 and 11; and MTX/ARA-C/PRED IT on day 1.
* Element HR-2: Patients receive DEXA on days 1-5; vindesine on days 1 and 6; DNR on day 5; MTX and ifosfamide every 12 hours on days 2-4 (5 doses); ASP on days 6 and 11; and MTX/ARA-C/PRED IT on day 1.\* NOTE: \*HR patients with CNS disease also receive IT therapy on day 5.
* Element HR-3: Patients receive DEXA on days 1-5; ARA-C every 12 hours on days 1-2 (4 doses); etoposide five times daily on days 3-5; ASP on days 6 and 11; and MTX/ARA-C/PRED IT on day 1.
* Arm V (extended reintensification therapy \[triple protocol III\] \[closed to accrual as of 6/30/2006\]): HR patients receive HR therapy elements 3, 2, and 1 as in arm IV following reintensification therapy as in arm II repeated the therapy element twice with 4-week interim maintenance phases in between. Patients then proceed to maintenance therapy.
* Interim maintenance/maintenance therapy: Patients receive MTX once weekly and MP daily until week 104.
* Radiotherapy: HR patients or patients with T-cell acute lymphoblastic leukemia or CNS disease undergo CNS radiotherapy.
PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4559
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Induction Prot I/Dexa - reinduction Prot III vincristine sulfate - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III radiation therapy - Induction Prot I/Pred - reinduction Prot III daunorubicin hydrochloride - Induction Prot I/Pred - reinduction Prot II thioguanine - Induction Prot I/Dexa - reinduction 2x Prot III mercaptopurine - Induction Prot I/Dexa - reinduction 2x Prot III methotrexate - Induction Prot I/Dexa - reinduction Prot III daunorubicin hydrochloride - Induction Prot I/Dexa - reinduction Prot III prednisone - Induction Prot I/Dexa - reinduction Prot III thioguanine - Induction Prot I/Dexa - reinduction Prot III radiation therapy - Induction Prot I/Pred - reinduction Prot III dexamethasone - Induction Prot I/Pred - reinduction Prot III methotrexate - Induction Prot I/Pred - reinduction Prot III thioguanine - Induction Prot I/Pred - reinduction Prot II daunorubicin hydrochloride - Induction Prot I/Pred - reinduction Prot III vincristine sulfate - Induction Prot I/Pred - reinduction Prot III vindesine - Induction Prot I/Pred - reinduction Prot III radiation therapy - Induction Prot I/Dexa - reinduction Prot II daunorubicin hydrochloride - Induction Prot I/Dexa - reinduction Prot II vincristine sulfate - Induction Prot I/Dexa - reinduction Prot II radiation therapy - Induction Prot I/Pred - reinduction Prot II dexamethasone - Induction Prot I/Pred - reinduction Prot II mercaptopurine - Induction Prot I/Pred - reinduction Prot II radiation therapy - Induction Prot I/Pred - reinduction Prot II vincristine sulfate - Induction Prot I/Dexa - reinduction 2x Prot III daunorubicin hydrochloride - Induction Prot I/Dexa - reinduction 2x Prot III dexamethasone - Induction Prot I/Dexa - reinduction 2x Prot III doxorubicin hydrochloride - Induction Prot I/Dexa - reinduction 2x Prot III vincristine sulfate - Induction Prot I/Dexa - reinduction 2x Prot III thioguanine - Induction Prot I/Dexa - reinduction 2x Prot III vindesine - Induction Prot I/Dexa - reinduction 2x Prot III radiation therapy - Induction Prot I/Pred - reinduction 2x Prot III asparaginase - Induction Prot I/Pred - reinduction 2x Prot III cytarabine - Induction Prot I/Pred - reinduction 2x Prot III daunorubicin hydrochloride - Induction Prot I/Pred - reinduction 2x Prot III dexamethasone - Induction Prot I/Pred - reinduction 2x Prot III ifosfamide - Induction Prot I/Pred - reinduction 2x Prot III vincristine sulfate - Induction Prot I/Pred - reinduction 2x Prot III radiation therapy - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III cytarabine - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III daunorubicin hydrochloride - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III vincristine sulfate - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III daunorubicin hydrochloride - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III thioguanine - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III ifosfamide - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III methotrexate - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III prednisone - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III radiation therapy - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III vincristine sulfate - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II cyclophosphamide - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II cytarabine - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II daunorubicin hydrochloride - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II ifosfamide - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II vincristine sulfate - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II radiation therapy - Induction Prot I/Pred - reinduction 6 HR courses + Prot II daunorubicin hydrochloride - Induction Prot I/Pred - reinduction 6 HR courses + Prot II etoposide - Induction Prot I/Pred - reinduction 6 HR courses + Prot II ifosfamide - Induction Prot I/Pred - reinduction 6 HR courses + Prot II methotrexate - Induction Prot I/Pred - reinduction 6 HR courses + Prot II vincristine sulfate - Induction Prot I/Pred - reinduction 6 HR courses + Prot II radiation therapy - Induction Prot I/Dexa - reinduction Prot III doxorubicin hydrochloride - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III prednisone - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III vindesine - Induction Prot I/Pred - reinduction 2x Prot III doxorubicin hydrochloride - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III asparaginase - Induction Prot I/Pred - reinduction 2x Prot III methotrexate - Induction Prot I/Dexa - reinduction Prot III asparaginase - Induction Prot I/Dexa - reinduction Prot III cytarabine - Induction Prot I/Dexa - reinduction Prot III cyclophosphamide - Induction Prot I/Dexa - reinduction Prot III dexamethasone - Induction Prot I/Dexa - reinduction Prot III ifosfamide - Induction Prot I/Dexa - reinduction Prot III methotrexate - Induction Prot I/Dexa - reinduction Prot III mercaptopurine - Induction Prot I/Dexa - reinduction Prot III vindesine - Induction Prot I/Pred - reinduction Prot III asparaginase - Induction Prot I/Pred - reinduction Prot III cyclophosphamide - Induction Prot I/Pred - reinduction Prot III cytarabine - Induction Prot I/Pred - reinduction Prot III doxorubicin hydrochloride - Induction Prot I/Pred - reinduction Prot III ifosfamide - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III mercaptopurine - Induction Prot I/Pred - reinduction Prot III mercaptopurine - Induction Prot I/Pred - reinduction Prot III prednisone - Induction Prot I/Dexa - reinduction Prot II asparaginase - Induction Prot I/Dexa - reinduction Prot II cyclophosphamide - Induction Prot I/Dexa - reinduction Prot II cytarabine - Induction Prot I/Dexa - reinduction Prot II mercaptopurine - Induction Prot I/Dexa - reinduction Prot II dexamethasone - Induction Prot I/Dexa - reinduction Prot II doxorubicin hydrochloride - Induction Prot I/Dexa - reinduction Prot II ifosfamide - Induction Prot I/Dexa - reinduction Prot II methotrexate - Induction Prot I/Dexa - reinduction Prot II prednisone - Induction Prot I/Dexa - reinduction Prot II thioguanine - Induction Prot I/Pred - reinduction Prot II cytarabine - Induction Prot I/Dexa - reinduction Prot II vindesine - Induction Prot I/Pred - reinduction Prot II asparaginase - Induction Prot I/Pred - reinduction Prot II cyclophosphamide - Induction Prot I/Pred - reinduction Prot II doxorubicin hydrochloride - Induction Prot I/Pred - reinduction Prot II ifosfamide - Induction Prot I/Pred - reinduction Prot II methotrexate - Induction Prot I/Pred - reinduction Prot II prednisone - Induction Prot I/Pred - reinduction Prot II vindesine - Induction Prot I/Dexa - reinduction 2x Prot III asparaginase - Induction Prot I/Dexa - reinduction 2x Prot III cytarabine - Induction Prot I/Dexa - reinduction 2x Prot III cyclophosphamide - Induction Prot I/Dexa - reinduction 2x Prot III ifosfamide - Induction Prot I/Dexa - reinduction 2x Prot III prednisone - Induction Prot I/Pred - reinduction 2x Prot III cyclophosphamide - Induction Prot I/Pred - reinduction 2x Prot III mercaptopurine - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III doxorubicin hydrochloride - Induction Prot I/Pred - reinduction 2x Prot III prednisone - Induction Prot I/Pred - reinduction 2x Prot III thioguanine - Induction Prot I/Pred - reinduction 2x Prot III vindesine - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III cyclophosphamide - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III dexamethasone - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III doxorubicin hydrochloride - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III etoposide - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III methotrexate - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III ifosfamide - Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III thioguanine - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III asparaginase - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III cytarabine - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III cyclophosphamide - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III dexamethasone - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III etoposide - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III mercaptopurine - Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III vindesine - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II mercaptopurine - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II asparaginase - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II dexamethasone - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II doxorubicin hydrochloride - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II thioguanine - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II etoposide - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II methotrexate - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II prednisone - Induction Prot I/Dexa - reinduction 6 HR courses + Prot II vindesine - Induction Prot I/Pred - reinduction 6 HR courses + Prot II asparaginase - Induction Prot I/Pred - reinduction 6 HR courses + Prot II cyclophosphamide - Induction Prot I/Pred - reinduction 6 HR courses + Prot II cytarabine - Induction Prot I/Pred - reinduction 6 HR courses + Prot II doxorubicin hydrochloride - Induction Prot I/Pred - reinduction 6 HR courses + Prot II dexamethasone - Induction Prot I/Pred - reinduction 6 HR courses + Prot II mercaptopurine - Induction Prot I/Pred - reinduction 6 HR courses + Prot II prednisone - Induction Prot I/Pred - reinduction 6 HR courses + Prot II thioguanine - Induction Prot I/Pred - reinduction 6 HR courses + Prot II vindesine -
- Primary Outcome Measures
Name Time Method Efficacy of dexamethasone vs prednisone during the induction phase End of Trial Event-free survival (EFS) and overall survival after initial remission in intermediate-risk and high-risk patients End of Trial Safety and efficacy of treatment reduction during reintensification in standard-risk patients End of Trial EFS after second delayed reintensification in intermediate-risk patients End of Trial Outcome after extended reintensification therapy in high-risk patients End of Trial
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (75)
LKH Leoben
🇦🇹Leoben, Austria
Landeskrankenhaus Feldkirch
🇦🇹Feldkirch-Tisis, Austria
Universitaet Kinderklinik
🇦🇹Graz, Austria
Innsbruck Universitaetsklinik
🇦🇹Innsbruck, Austria
Landeskrankenhaus Klagenfurt
🇦🇹Klagenfurt, Austria
A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung
🇦🇹Linz, Austria
Landes-Kinderkrankenhaus
🇦🇹Linz, Austria
St. Johanns-Spital
🇦🇹Salzburg, Austria
St. Anna Children's Hospital
🇦🇹Vienna, Austria
Universitaets-Kinderspital beider Basel
🇨🇭Basel, Switzerland
Ospedale "la Carita", Locarno
🇨🇭Locarno, Switzerland
Kinderspital Luzern
🇨🇭Lucerne 16, Switzerland
Ostschweizer Kinderspital
🇨🇭St. Gallen, Switzerland
Universitaetsklinikum Goettingen
🇩🇪Goettingen, Germany
Klinikum Kemperhof Koblenz
🇩🇪Koblenz, Germany
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
Universitatsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Klinikum Coburg
🇩🇪Coburg, Germany
Universitaetsklinikum Halle
🇩🇪Halle, Germany
Klinikum Augsburg
🇩🇪Augsburg, Germany
Charite University Hospital - Campus Virchow Klinikum
🇩🇪Berlin, Germany
Kinderklinik
🇩🇪Giessen, Germany
Vestische Kinderklinik Universitaetsklinik Witten/Herdecke
🇩🇪Datteln, Germany
Caritas-Krankenhaus Bad Mergentheim
🇩🇪Bad Mergentheim, Germany
Klinikum Lippe - Detmold
🇩🇪Detmold, Germany
Kinderklinik - Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Klinikum Duisburg
🇩🇪Duisburg, Germany
Helios Klinikum Berlin
🇩🇪Berlin, Germany
Kinderklinik der Universitaet Bonn
🇩🇪Bonn, Germany
Krankenhaus Dornbirn
🇦🇹Dornbirn, Austria
Klinikum Schwerin
🇩🇪Schwerin, Germany
Staedtisches Klinikum - Howedestrase
🇩🇪Braunschweig, Germany
Klinikum Bayreuth
🇩🇪Bayreuth, Germany
Universitaets-Kinderklinik Heidelberg
🇩🇪Heidelberg, Germany
Kantonsspital Aarau
🇨🇭Aarau, Switzerland
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, Germany
Staedtisches Klinik - Kinderklinik
🇩🇪Mannheim, Germany
Universitaetsklinikum Giessen und Marburg GmbH - Marburg
🇩🇪Marburg, Germany
Johanniter-Kinderklinik
🇩🇪St. Augustin, Germany
Universitatsklinikum der MA
🇩🇪Magdeburg, Germany
Kinderklink Siegen Deutsches Rotes Kreuz
🇩🇪Siegen, Germany
Klinikum der Stadt Wolfsburg
🇩🇪Wolfsburg, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl
🇩🇪Cologne, Germany
Children's Hospital
🇩🇪Cologne, Germany
Klinikum Dortmund
🇩🇪Dortmund, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Universitaets - Kinderklinik
🇩🇪Jena, Germany
Universitaetskinderklinik - Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen
🇩🇪Heilbronn, Germany
St. Annastift Krankenhaus
🇩🇪Ludwigshafen, Germany
Universitaets - Kinderklinik - Luebeck
🇩🇪Luebeck, Germany
Gemeinschaftskrankenhaus
🇩🇪Herdecke, Germany
Universitaetsklinikum des Saarlandes
🇩🇪Homburg, Germany
Staedtisches Klinikum Karlsruhe gGmbH
🇩🇪Karlsruhe, Germany
Klinikum Kassel
🇩🇪Kassel, Germany
Klinikum Minden
🇩🇪Minden, Germany
Krankenhaus Muenchen Schwabing
🇩🇪Munich, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Krankenanstalt Mutterhaus der Borromaerinnen
🇩🇪Trier, Germany
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Olgahospital
🇩🇪Stuttgart, Germany
Kinderklinik - Universitaetsklinikum Rostock
🇩🇪Rostock, Germany
Saarbrucker Winterbergkliniken
🇩🇪Saarbrucken, Germany
St. Marienhospital - Vechta
🇩🇪Vechta, Germany
Universitaets - Kinderklinik Wuerzburg
🇩🇪Wuerzburg, Germany
Reinhard-Nieter-Krankenhaus
🇩🇪Wilhelmshaven, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Carl - Thiem - Klinkum Cottbus
🇩🇪Cottbus, Germany
Kinderklinik Kohlhof
🇩🇪Neunkirchen, Germany
Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Cnopf'sche Kinderklinik
🇩🇪Nuremberg, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
University Children's Hospital
🇨🇭Zurich, Switzerland