International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma
- Conditions
- Lymphoblastic Lymphoma, Childhood
- Interventions
- Registration Number
- NCT04043494
- Lead Sponsor
- University Hospital Muenster
- Brief Summary
Primary objectives:
* Randomization R1, all patients eligible: To examine, whether the cumulative incidence of relapses with involvement of the CNS (CNS relapse, pCICR) can be decreased by a modified induction therapy including dexamethasone (experimental arm) instead of prednisone (standard arm)
* Randomization R2, only patients with high risk LBL eligible: to examine, whether the probability of event-free survival (pEFS) in these patients can be improved by receiving an intensified treatment arm versus a standard treatment arm (as used in the EURO-LB 02)
- Detailed Description
The trial LBL 2018 is a collaborative prospective, multi-national, multi-center, randomized clinical trial for the treatment of children and adolescents with newly diagnosed lymphoblastic lymphoma.
The LBL 2018 trial will be open for the qualified centers of following participating study Groups (core study cohort): AIEOP (Italy), BFM (Austria, Czech Republic, Germany, Switzerland), BSPHO (Belgium), CoALL (Germany), DCOG (The Netherlands), NOPHO (Denmark, Finland, Norway, Sweden), PPLLSG (Poland), SEHOP (Spain) and SFCE (France). HKPHOSG (Hong Kong), HPOG (Hungary), ISPHO (Israel), NSPHO (Moscow), SHOP (Portugal) and SPS (Slovak Republic) start patient recruitment into the extended study cohort (without randomization). Over the trial period study groups may switch from the extended study cohort to the core study cohort.
Primary objectives:
* Randomization R1, all patients eligible: To examine, whether the cumulative incidence of relapses with involvement of the CNS (CNS relapse, pCICR) can be decreased by a modified induction therapy including dexamethasone (experimental arm) instead of prednisone (standard arm)
* Randomization R2, only patients with high risk LBL eligible: to examine, whether the probability of event-free survival (pEFS) in these patients can be improved by receiving an intensified treatment arm versus a standard treatment arm (as used in the EURO-LB 02)
Patients are stratified into 3 different risk groups according to CNS status, immunophenotype, genetic markers and stage of disease at diagnosis: high risk group (HR), standard risk group I/II (SR I/II) and standard risk group (SR).
Patients in the risk groups SR I/II and SR are randomized (R1) in two arms after a cytoreductive prephase with prednisone. Patients in standard arm receive the standard induction phase with prednisone. Patients in the experimental arm receive an induction phase with dexamethasone instead of prednisone.
In SR group, induction phase is followed by the consolidation phase, the non-HR extra-compartment phase with HD-MTX (high-dose methotrexate), the reintensification phase and the maintenance therapy for the total therapy duration of 24 months. In SR I/II group, patients receive no reintensification phase. The Induction phase is followed by the consolidation phase, the non-HR extra-compartment phase and the maintenance therapy for the total therapy duration of 24 months.
Patients in the HR group are eligible for randomization (R1) as outlined above. In addition high risk patients are eligible for second randomization (R2) at the end of induction phase. In the standard arm, HR-patients receive the consolidation phase and the non-HR extra-compartment phase. In the experimental arm, HR-patients receive a consolidation phase including two additional doses of PEG asparaginase and the HR-intensified extra-compartment phase consisting of two high risk courses alternating with two HD-MTX courses. Either phase is followed by the reintensification phase and the maintenance therapy for the total therapy duration of 24 months.
Patients with involvement of the CNS (CNS positive) are stratified to the high risk group (HR) and are eligible for both randomizations (R1 and R2). Additionally, patients with CNS involvement (CNS positive) receive intensified intrathecal therapy. Intrathecal therapy consists of TIT (triple intrathecal therapy) after diagnosis of CNS involvement. TIT is administered twice weekly until clearance of blasts in the cerebrospinal fluid is achieved. Further intrathecal therapy is provided at the same points of time as for patients without CNS involvement, but TIT instead of MTX IT. In addition, patients receive four additional doses of TIT during maintenance. Cranial irradiation is omitted for patients with CNS involvement.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 683
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SR I/II: R1 into protocol Ia-Pred Cytarabine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred Daunorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred Methotrexate 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred PEG asparaginase 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred Vincristine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Cyclophosphamide 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Cytarabine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Dexamethasone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Daunorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa PEG asparaginase 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR: R1 into protocol Ia-Pred Dexamethasone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Methotrexate 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred PEG asparaginase 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Thioguanine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Vincristine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Doxorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Methotrexate 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa PEG asparaginase 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Prednisone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Prednisolone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Thioguanine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Prednisolone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Thioguanine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Daunorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase PEG asparaginase 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Vincristine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Dexamethasone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase PEG asparaginase 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Prednisone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Dexamethasone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Doxorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase PEG asparaginase 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Vindesine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Methotrexate 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase PEG asparaginase 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Prednisone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Vindesine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR I/II: R1 into protocol Ia-Pred Cyclophosphamide 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred Prednisone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Pred Prednisolone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Methotrexate 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Prednisone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Prednisolone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR I/II: R1 into protocol Ia-Dexa Vincristine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment Phase (protocol M) 5. maintenance therapy SR: R1 into protocol Ia-Pred Cyclophosphamide 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Cytarabine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Daunorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Prednisolone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Doxorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Pred Prednisone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Cyclophosphamide 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Cytarabine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Dexamethasone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Daunorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Cyclophosphamide 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy SR: R1 into protocol Ia-Dexa Vincristine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Cytarabine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Dexamethasone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Doxorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Methotrexate 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into non-HR extra-compartment phase Prednisone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Cytarabine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Cyclophosphamide 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Daunorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Doxorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Methotrexate 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Prednisolone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Thioguanine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Cyclophosphamide 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Cytarabine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase Vincristine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib) 4. non-HR extra-compartment phase (protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Daunorubicin 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Ifosfamide 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase 6-Mercaptopurine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Methotrexate 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Vincristine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Prednisone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Prednisolone 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Pred" and R2 into HR extra-compartment phase Thioguanine 1. cytoreductive prephase with prednisone 2. standard induction phase (protocol Ia-prednisone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Cytarabine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Cyclophosphamide 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Doxorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Dexamethasone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Daunorubicin 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Ifosfamide 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Prednisolone 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Thioguanine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy HR: R1 into "Dexa" and R2 into HR extra-compartment phase Vincristine 1. cytoreductive prephase with prednisone 2. experimental induction phase (protocol Ia-dexamethasone) 3. consolidation phase (protocol Ib\*) 4. HR extra-compartment phase (intensified protocol M) 5. reintensification phase (protocol II) 6. maintenance therapy
- Primary Outcome Measures
Name Time Method Cumulative incidence of relapse with involvement of the CNS (CNS-relapse, pCICR) through study completion, maximal 7.25 years The time to relapse is defined as the time from randomization to the first relapse or the date of last follow-up. Other events (non-response, progressive disease, relapse, second malignancy or death before and in CR) will be taken into account as competing events.
Estimated probability of event-free survival (pEFS) through study completion, maximal 7.25 years The pEFS is defined as the time from randomization to the first event (non-response, progressive disease, relapse, second malignancy or death from any cause) or date of last follow-up.
- Secondary Outcome Measures
Name Time Method Survival (pOS) through study completion, maximal 7.25 years Survival (pOS) is defined as time from diagnosis to death due to any cause or to the date of last contact for patients alive
Frequency of treatment-related toxicity overall and in specific protocol elements, randomized arms and during follow up through study completion, maximal 7.25 years Frequency of treatment-related mortality overall and in specific protocol elements, randomized arms and during follow up through study completion, maximal 7.25 years Frequency of adverse events of interest and severe adverse events overall through study completion, maximal 7.25 years Cumulative incidence of relapses in association with molecular markers through study completion, maximal 7.25 years Cumulative incidence of relapses in association with minimal residual disease results through study completion, maximal 7.25 years Rate of evaluable patients for risk group stratification during recruitment
Trial Locations
- Locations (226)
Univ.Klinik für Kinder- und Jugendheilkunde Graz, Klin. Abteilung für pädiatrische Hämato-Onkologie
🇦🇹Graz, Austria
Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck, Universitätsklinik für Pädiatrie I
🇦🇹Innsbruck, Austria
Kepler Universitätsklinikum, Med Campus IV / Onkologie
🇦🇹Linz, Austria
LKH Salzburg, Universitätsklinik für Kinder- und Jugendheilkunde, Kinderonkologie
🇦🇹Salzburg, Austria
St. Anna Kinderspital
🇦🇹Wien, Austria
Hôpital Universitaire des Enfants Reine Fabiola (ULB), Pédiatrie hémato-oncologie
🇧🇪Brussels, Belgium
University Hospital Brussels, Pediatrische oncologie
🇧🇪Brussel, Belgium
Cliniques Universitaires Saint-Luc (UCL), Hématologie et oncologie pédiatrique
🇧🇪Brussel, Belgium
UZ Antwerpen Kinderhemato-oncologie
🇧🇪Edegem, Belgium
University Hospital Gent Pediatrische hemato-oncologie
🇧🇪Gent, Belgium
University Hospitals Leuven, Kinderhemato-oncologie
🇧🇪Leuven, Belgium
CHR Citadelle Hémato - oncologie pédiatrique
🇧🇪Montegnée, Belgium
Hong Kong Children's Hospital
🇨🇳Hong Kong, China
Dept. of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University Cernopolni
🇨🇿Brno, Czechia
Dept. of Pediatric Hematology and Oncology. University Hospital Motol and 2nd Medical School, Charles University
🇨🇿Praha, Czechia
University Hospital Aalborg, Nord, Department of Pediatrics
🇩🇰Aalborg, Denmark
Aarhus University Hospital, Department of Pediatrics
🇩🇰Aarhus, Denmark
Børneonkologisk afsnit 5054, BørneUngeKlinikken, Juliane Marie Centret, Rigshospitalet
🇩🇰Kobenhavn, Denmark
H.C. Andersens Children Hospital, Odense University Hospital
🇩🇰Odense, Denmark
Helsinki University Hospital, Department of Pediatric Hematology and Oncology
🇫🇮Helsinki, Finland
Kuopio University Hospital, Department of Pediatric Hematology and Oncology
🇫🇮Kuopio, Finland
University Hospital of Oulu, Paediatric Haematology and Oncology
🇫🇮Oulu, Finland
Tampere University Hospital, Paediatric Haematology and Oncology
🇫🇮Tampere, Finland
Turku University Hospital, Paediatric and Adolescent Haematology and Oncology
🇫🇮Turku, Finland
Service d'oncolologie, Hématologie pédiatrique. CHU Amiens, Avenue René Laënnec - SALOUEL
🇫🇷Amiens, France
Pôle Femme Mère Enfant ; Unité d'Hématologie/Oncologie pédiatrique, CHU Angers
🇫🇷Angers, France
Hématologie Oncologie pédiatrique, CHRU Besançon
🇫🇷Besançon, France
Hôpital de Enfants, Unité Onco-Hématologie Pédiatrique, Groupe Hospitalier Pellegrin
🇫🇷Bordeaux, France
Département de Pédiatrie et Génétique Médicale CHRU Morvan
🇫🇷Brest, France
Unité d'hémato-immuno-oncologie pédiatrique. Centre Hospitalier Universitaire niveau 1 - bâtiment FEH
🇫🇷Caen, France
Unité Onco- Hématologie Pédiatrique CHU Estaing 1 place Lucie-Aubrac
🇫🇷Clermont-Ferrand, France
Service Immuno-Hématologie Oncologie Pédiatrique
🇫🇷Dijon, France
Service onco hématologie pédiatrique CHU de Grenoble site Nord - Hôpital Couple enfant
🇫🇷Grenoble, France
Unité d'hématologie pédiatrique CHRU de Lille - Hôpital Jeanne de Flandre
🇫🇷Lille, France
Service d'Hématologie - Oncologie pédiatrique CHU Limoges - Hôpital de la mère et de l'enfant
🇫🇷Limoges, France
Service d'immuno-hématologie pédiatrique et de transplantation de moelle osseuse, CHU de Lyon HCL - GH Est-Institut d'hématologie et d'oncologie pédiatrique IHOP
🇫🇷Lyon, France
Service de Pédiatrie et hématologie pédiatrique, CHU de Marseille - Hôpital de la Timone
🇫🇷Marseille, France
UAM Hématologie et Oncologie Pédiatrique, CHU de Montpellier - Hôpital Arnaud de Villeneuve
🇫🇷Montpellier, France
Service d'hématologie et oncologie pédiatriques, Hôpital enfant-adolescent, CHU NANTES
🇫🇷Nantes, France
Service d'hémato-oncologie pédiatrique CHU NICE - Hôpital l'Archet 2
🇫🇷Nice, France
service d'oncologie pédiatrique, institut Curie
🇫🇷Paris, France
Service Hémato-immuno- oncologie- CHU PARIS Armand Trousseau
🇫🇷Paris, France
Service d' hémato-immunologie CHU Paris - Hôpital Robert Debré
🇫🇷Paris, France
Service Oncologie-Hématologie pédiatrique CHU de Poitiers
🇫🇷Poitiers, France
Service d'Hémato-Oncologie Pédiatrique- American Hospital
🇫🇷Reims, France
Pôle pédiatrie Hémato-cancérologie pédiatrique- CHU RENNES - Hôpital sud
🇫🇷Rennes, France
Service d'Hemato-Oncologie Pediatrique CHU Rouen
🇫🇷Rouen, France
service d'oncologie pédiatrique, hopital Félix Guyon
🇫🇷Saint-Denis, France
Pôle mère enfant-Unité Hématologie - Oncologie pédiatrique - CHU Hôpital NORD
🇫🇷Saint-Priest-en-Jarez, France
Service d'Onco-Hematologie Pediatrique CHU STRASBOURG -Hôpital de Hautepierre
🇫🇷Strasbourg, France
Service Pédiatrie - Hématologie Immunologie Oncologie - CHU Toulouse
🇫🇷Toulouse, France
Service d'hémato-oncologie pédiatrique- CHU de Nancy - Hôpital de Brabois Enfant
🇫🇷Vandœuvre-lès-Nancy, France
Dépt de Pédiatrie Gustave Roussy
🇫🇷Villejuif, France
Universitätsklinikum Aachen .Klinik für Kinder - und Jugendmedizin Hämatologie / Onkologie
🇩🇪Aachen, Germany
Klinikum Augsburg ,Schwäbisches Kinderkrebszentrum. I. Klinik für Kinder und Jugendliche Hämatologie / Onkologie
🇩🇪Augsburg, Germany
HELIOS Klinikum Berlin-Buch, Kinderklinik, Pädiatrische Hämatologie und Onkologie
🇩🇪Berlin, Germany
Charité Campus Virchow-Klinikum, Zentrum für Kinder- und Jugendmedizin- Abt. Hämatologie / Onkologie
🇩🇪Berlin, Germany
Evangelisches Krankenhaus Bielefeld GmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie
🇩🇪Bielefeld, Germany
Zentrum für Kinderheilkunde der Universität Bonn, Abt. Päd. Hämatologie / Onkologie
🇩🇪Bonn, Germany
Städtisches Klinikum Braunschweig gGmbH, Zentrum für Kinder- und Jugendmedizin
🇩🇪Braunschweig, Germany
Klinikum Bremen-Mitte gGmbH, Prof.-Hess-Kinderklinik,Pädiatrische Onkologie und Hämatologie
🇩🇪Bremen, Germany
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie
🇩🇪Chemnitz, Germany
Carl-Thiem-Klinikum, Kinderklinik, Station 5e
🇩🇪Cottbus, Germany
Vestische Kinderklinik, Universität Witten / Herdecke
🇩🇪Datteln, Germany
Klinikum Dortmund gGmbH, Klinik für Kinder- und Jugendmedizin, Station K1, Abt. Päd. Onkologie / Hämatologie
🇩🇪Dortmund, Germany
Universitätsklinik Carl Gustav Carus der TU Dresden, Klinik für Kinder- und Jugendmedizin
🇩🇪Dresden, Germany
Universitätsklinikum Düsseldorf, Zentrum für Kinder- und Jugendmedizin, Klinik für Päd. Hämatologie und Onkologie
🇩🇪Düsseldorf, Germany
HELIOS Klinikum Erfurt GmbH, Klinik für Kinder- und Jugendmedizin, Päd. Onkologie / Hämatologie
🇩🇪Erfurt, Germany
Universitätsklinikum Erlangen, Klinik für Kinder- und Jugendmedizin, Pädiatrische Onkologie / Hämatologie
🇩🇪Erlangen, Germany
Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin, Hämatologie / Onkologie
🇩🇪Essen, Germany
Universitätsklinikum Frankfurt, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie
🇩🇪Frankfurt, Germany
Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie
🇩🇪Freiburg, Germany
Universitätsklinikum Gießen und Marburg, Standort Gießen, Zentrum für Kinderhämatologie und -onkologie
🇩🇪Gießen, Germany
Universitätsklinikum Greifswald KdöR, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Onkologie und Hämatologie
🇩🇪Greifswald, Germany
Georg-August-Universität Universitäts-Kinderklinik, Pädiatrie I
🇩🇪Göttingen, Germany
Universitätsklinikum Halle (Saale), Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie
🇩🇪Halle, Germany
Universitätsklinikum Hamburg Eppendorf, Zentrum für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover, Kinderheilkunde, Päd. Hämatologie / Onkologie
🇩🇪Hannover, Germany
Universitäts-Kinderklinik Heidelberg, Abt. Hämatologie / Onkologie
🇩🇪Heidelberg, Germany
Gemeinschaftskrankenhaus Herdecke, Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie
🇩🇪Herdecke, Germany
Universitätskliniken für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie, Geb. 9
🇩🇪Homburg, Germany
Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin
🇩🇪Jena, Germany
Städtisches Klinikum Karlsruhe gGmbH, Kinderklinik, Station S 24
🇩🇪Karlsruhe, Germany
Klinikum Kassel Gesundheit Nordhessen Holding AG, Klinik für pädiatrische Hämatologie und Onkologie
🇩🇪Kassel, Germany
Universitätsklinikum Schleswig Holstein Campus Kiel, Klinik für Allgemeine Pädiatrie, Päd. Onkologie / Hämatologie
🇩🇪Kiel, Germany
Gemeinschaftsklinikum Mittelrhein Kemperhof, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie
🇩🇪Koblenz, Germany
HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Päd. Hämatologie/Onkologie
🇩🇪Krefeld, Germany
Klinikum der Universität zu Köln, Klinik für Kinder- und Jugendmedizin, Abt. Kinderonkologie und -hämatologie
🇩🇪Köln, Germany
Universitätsklinikum Leipzig, Klinik für Kinder und Jugendliche, Abt. Päd. Hämatologie / Onkologie
🇩🇪Leipzig, Germany
Universitätsklinikum Schleswig Holstein Campus Lübeck, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie
🇩🇪Lübeck, Germany
Universitätsklinikum Magdeburg A. ö. R., Kinderklinik, Päd. Hämatologie / Onkologie
🇩🇪Magdeburg, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie
🇩🇪Mainz, Germany
Klinikum Mannheim gGmbH, Universitäts-Kinderklinik, Päd. Onkologie /Hämatologie
🇩🇪Manheim, Germany
Johannes Wesling Klinikum Minden, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie, Station E 22
🇩🇪Minden, Germany
Klinikum der LMU, Dr. von Haunersches Kinderspital, Pädiatrische Hämatologie / Onkologie
🇩🇪München, Germany
Klinikum Schwabing, Kinderklinik der TU Päd. Hämatologie / Onkologie, Station 24d
🇩🇪München, Germany
Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie
🇩🇪Münster, Germany
Diakonie Neuendettelsau, Kliniken Hallerwiese / Cnopf'sche Kinderklinik, Pädiatrische Hämatologie /Onkologie
🇩🇪Nürnberg, Germany
Klinikum Oldenburg AöR, Zentrum für Kinder- und Jugendmedizin, Abt. Hämatologie / Onkologie
🇩🇪Oldenburg, Germany
Universitätsklinikum Regensburg, Klinik für Kinder- und Jugendmedizin, Abt. Päd. Hämatologie, Onkologie, SZT
🇩🇪Regensburg, Germany
Universitätsklinikum Rostock, Kinder- und Jugendklinik, Päd. Hämatologie und Onkologie
🇩🇪Rostock, Germany
Asklepios Klinik St. Augustin GmbH, Kinder- und Jugendmedizin, Kinder-Hämatologie und Onkologie
🇩🇪Sankt Augustin, Germany
HELIOS Kliniken Schwerin GmbH, Klinik für Kinder- und Jugendmedizin, Station A1
🇩🇪Schwerin, Germany
Klinikum Stuttgart, Olgahospital Zentrum für Kinder- und Jugendmedizin Pädiatrie 5 (Onkologie, Hämatologie, Immunologie)
🇩🇪Stuttgart, Germany
Klinikum Mutterhaus der Borromäerinnen gGmbH, Pädiatrische Abteilung
🇩🇪Trier, Germany
Universitätsklinik Tübingen, Klinik für Kinderheilkunde und Jugendmedizin, Päd. Hämatologie / Onkologie
🇩🇪Tübingen, Germany
Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie
🇩🇪Ulm, Germany
Universitätskinderklinik Würzburg, Päd. Onkologie und Hämatologie
🇩🇪Würzburg, Germany
2nd Dep. of Pediatrics, Semmelweis Univ
🇭🇺Budapest, Hungary
Heim Pal Children Hospital
🇭🇺Budapest, Hungary
Dep. of Pediatrics, Univ. of Debrecen
🇭🇺Debrecen, Hungary
Children's Treating Center, Miskolc
🇭🇺Miskolc, Hungary
Dep. of Pediatrics, University of Pecs
🇭🇺Pécs, Hungary
Dep. of Pediatrics, Univ. of Szeged
🇭🇺Szeged, Hungary
Our Lady's Children's Hospital Crumlin
🇮🇪Dublin, Ireland
Children's Hospital at Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Ruth Rappaport Children's Hospital, Rambam Medical Center
🇮🇱Haifa, Israel
Children's Hospital at Hadassah, Ein Kerem Medical Center
🇮🇱Jerusalem, Israel
Schneider Children's hospital, Rabin Medical Center
🇮🇱Petah tikva, Israel
Edmond and Lily Safra Children's Hospital, Sheba Medical Center
🇮🇱Ramat Gan, Israel
Dana Children's Hospital, Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliero Universitaria Delle Marche
🇮🇹Ancona, Italy
University Hospital Consorziale Policlinico
🇮🇹Bari, Italy
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Azienda Ospedaliero-Universitaria Di Bologna IRCCS
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
🇮🇹Brescia, Italy
ARNAS G. Brotzu
🇮🇹Cagliari, Italy
Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
🇮🇹Catania, Italy
University Hospital Of Ferrara
🇮🇹Cona, Italy
U. O. di Pediatria- Azienda Ospedaliera Annunziata
🇮🇹Cosenza, Italy
Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria - Università di Ferrara
🇮🇹Ferrara, Italy
Azienda Ospedaliera Universitaria Meyer IRCCS
🇮🇹Florence, Italy
Giannina Gaslini Institute For Scientific Hospitalization And Care
🇮🇹Genova, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria di Modena
🇮🇹Modena, Italy
Fondazione IRCCS San Gerardo Dei Tintori
🇮🇹Monza, Italy
L'Azienda Ospedaliera Di Rilievo Nazionale Santobono-Pausilipon
🇮🇹Naples, Italy
S.C. Ematologia Oncologica- Ospedale "Pausilipon"
🇮🇹Napoli, Italy
Azienda Ospedale-Università Padova
🇮🇹Padova, Italy
ARNAS Civico Di Cristina Benfratelli
🇮🇹Palermo, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Azienda Sanitaria Locale Di Pescara
🇮🇹Pescara, Italy
Azienda Unità Sanitaria della Romagna
🇮🇹Rimini, Italy
Sezione Ematologia- Dipart. Biotecnico Cellulare ed Ematologia- Università "La Sapienza"
🇮🇹Roma, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
Casa Sollievo Della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
Oncologia Pediatrica,- Ospedale "R. Silvestrini"
🇮🇹San Sisto, Italy
Azienda Ospedaliera Universitaria Città Della Salute E Della Scienza Di Torino
🇮🇹Torino, Italy
Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo
🇮🇹Trieste, Italy
Azienda Socio Sanitaria Territoriale Dei Sette Laghi
🇮🇹Varese, Italy
Azienda Ospedaliera Universitaria Integrata di Verona
🇮🇹Verona, Italy
Princess Maxima Centre for Pediatric Oncology
🇳🇱Utrecht, Netherlands
Haukeland University Hospital in Bergen
🇳🇴Bergen, Norway
University Hospital Northern Norway
🇳🇴Tromsø, Norway
St Olavs Hospital in Trondheim
🇳🇴Trondheim, Norway
Department of Pediatric Oncology and Hematology, Medical University of Bialystok
🇵🇱Białystok, Poland
Department of Pediatric Hematology and Oncology, Nicolaus Copernicus University
🇵🇱Bydgoszcz, Poland
Department of Pediatric Hematology and Oncology, Center of Pediatrics and Oncology in Chorzów
🇵🇱Chorzów, Poland
Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdansk
🇵🇱Gdańsk, Poland
Department of Pediatric Oncology and Hematology, Center of Pediatrics in Kielce
🇵🇱Kielce, Poland
Department of Pediatric Oncology/Hematology, Institute of Pediatrics, Medical College Jagiellonian University
🇵🇱Kraków, Poland
Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin
🇵🇱Lublin, Poland
Department of Pediatric Oncology and Hematology, Provincial Specialist Children's Hospital
🇵🇱Olsztyn, Poland
Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences
🇵🇱Poznań, Poland
Department of Paediatric Oncology and Haematology, University of Rzeszów, Department of Pediatrics
🇵🇱Rzeszów, Poland
Department of Pediatrics, Children Hematology nad Oncology, Pomeranian Medical University
🇵🇱Szczecin, Poland
Department of Pediatrics, Hematology and Oncology, Medical University of Warsaw
🇵🇱Warsaw, Poland
Department of Pediatric Oncology, Children's Memorial Health Institute
🇵🇱Warsaw, Poland
Department of Bone Marrow Transplantation, Children Oncology and Hematology, Wroclaw Medical University
🇵🇱Wrocław, Poland
Department of Pediatric Hematology and Oncology, Silesian Medical University in Katowice
🇵🇱Zabrze, Poland
Department of Pediatrics, Oncology, Hematology and Diabetology, Institute of Pediatrics, Medical University of Lodz
🇵🇱Łódź, Poland
Centro Hospitalar e Universitário de Coimbra
🇵🇹Coimbra, Portugal
Instituto Português de Oncologia - Francisco Gentil - Libosa
🇵🇹Lisboa, Portugal
Instituto Português de Oncologia - Francisco Gentil - Porto
🇵🇹Porto, Portugal
Oncological center of regional Children's Hospital
🇷🇺Ekaterinburg, Russian Federation
National Center for Pediatric Hematology, Oncology and Immunology Moscow
🇷🇺Moscow, Russian Federation
Department of pediatric oncology and hematology, Children´s Faculty Hospital
🇸🇰Banská Bystrica, Slovakia
Department of pediatric hematology and oncology, National Institute of Children's Diseases
🇸🇰Bratislava, Slovakia
Department of pediatric hematology and oncology, Children´s University Hospital
🇸🇰Košice, Slovakia
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitario Torrecárdenas
🇪🇸Almería, Spain
Hospital Materno-Infantil de Badajoz
🇪🇸Badajoz, Spain
Hospital Universitario Cruces
🇪🇸Baracaldo, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Donostia
🇪🇸Donostia, Spain
Hospital Sant Joan de Déu
🇪🇸Esplugues De Llobregat, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Complejo Hospitalario Universitario Insular Materno Infantil
🇪🇸Las Palmas De Gran Canaria, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Hospital Universitari Son Espases
🇪🇸Palma De Mallorca, Spain
Hospital Virgen del Camino
🇪🇸Pamplona, Spain
Complejo Hospitalario Universitario de Vigo
🇪🇸Pontevedra, Spain
Hospital Universitario Nuestra Señora de Candelaria
🇪🇸Santa Cruz De Tenerife, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Clínico Universitario de Santiago
🇪🇸Santiago De Compostela, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Virgen de la Salud
🇪🇸Toledo, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitari i Politècnic La Fe
🇪🇸Valencia, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸Valladolid, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Barncancercentrum, Drottning Silvias Barn och Ungdomssjukhus, Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Barnonkologiska enheten, Barn och Ungdomsmedicinska kliniken, Universitetssjukhuset i Linköping
🇸🇪Linköping, Sweden
Barnonkologi, Skåne Universitetssjukhus
🇸🇪Lund, Sweden
Barncanceravdelningen Astrid Lindgrens Barnsjukhus, Nya Karolinska Universitetssjukhuset
🇸🇪Stockholm, Sweden
Barnonkologiska avdelningen, Barn 3, Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
Barnavdelningen för blod- och tumörsjukdomar 95A, Akademiska sjukhuset
🇸🇪Uppsala, Sweden
Kantonsspital Aarau
🇨🇭Aarau, Switzerland
Universitäts-Kinderspital beider Basel (UKBB)
🇨🇭Basel, Switzerland
Ospedale San Giovanni
🇨🇭Bellinzona, Switzerland
Inselspital Bern, University of Bern
🇨🇭Bern, Switzerland
HUG Hôpitaux Universitaires de Genève
🇨🇭Geneva, Switzerland
CHUV - Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Luzerner Kantonspital - Kinderspital Luzern
🇨🇭Luzern, Switzerland
Ostschweizer Kinderspital
🇨🇭Sankt Gallen, Switzerland
Universitäts-Kinderspital Zürich
🇨🇭Zürich, Switzerland