NCT04043494

International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma

LBL 2018 - International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 683 (estimated)
• Sponsor: University Hospital Muenster · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lymphoblastic Lymphoma, Childhood

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Part of standard chemotherapy and included in the experimental treatment phase protocol Ib\* (Randomization 2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)
DRUG	Cytarabine	No involvement of CNS: Part of standard chemotherapy and included in the experimental treatment phase protocol Ib\* (Randomization 2) and in the experimental treatment phase Intensified Protocol M (Randomization R2). Involvement of CNS: Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)
DRUG	Dexamethasone	Part of the experimental therapy in Randomization R1 (Protocol Ia-Dexamethasone) and in Randomization R2 (Intensified Protocol M)
DRUG	Daunorubicin	Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)
DRUG	Doxorubicin	Part of standard chemotherapy
DRUG	Ifosfamide	Part of the experimental therapy in Randomization R2 (Intensified Protocol M)
DRUG	6-Mercaptopurine	Part of standard chemotherapy and included in the experimental treatment phase protocol Ib\* (Randomization 2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)
DRUG	Methotrexate	Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2)
DRUG	PEG asparaginase	Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1) and in the experimental treatment phase Protocol Ib\* (Randomization R2)
DRUG	Prednisone	Part of standard chemotherapy
DRUG	Prednisolone	No involvement of CNS: Part of standard chemotherapy. Involvement of CNS: Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1), in the experimental treatment phase Protocol Ib\* (Randomization R2) and in the experimental treatment phase Intensified Protocol M (Randomization R2
DRUG	Thioguanine	Part of standard chemotherapy
DRUG	Vincristine	Part of standard chemotherapy and included in the experimental treatment phase Protocol Ia-Dexamethasone (Randomization R1) and in the experimental treatment phase Intensified Protocol M (Randomization R2)
DRUG	Vindesine	Part of the experimental therapy in Randomization R2 (Intensified Protocol M)

Timeline

• Start date: 2019-08-23
• Primary completion: 2027-11-22
• Completion: 2027-11-22
• First posted: 2019-08-02
• Last updated: 2025-03-21

Locations

228 sites across 21 countries: Austria, Belgium, China, Czechia, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Norway, Poland, Portugal, Russia, Slovakia, Spain, Sweden, Switzerland