International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma
Phase 3
Recruiting
- 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
Inclusion Criteria
Not provided
Exclusion Criteria
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
Scroll for more (216 remaining)Univ.Klinik für Kinder- und Jugendheilkunde Graz, Klin. Abteilung für pädiatrische Hämato-Onkologie🇦🇹Graz, Austria