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

• ClinicalTrials.gov Identifier: NCT04043494
• Recruitment Status: Recruiting
• First Posted: August 2, 2019
• Last Update Posted: December 16, 2022
• Sponsor: University Hospital Muenster
• Collaborator: Deutsche Krebshilfe e.V., Bonn (Germany)
• Information provided by (Responsible Party): University Hospital Muenster

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Lymphoblastic Lymphoma, Childhood	Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Daunorubicin; Drug: Doxorubicin; Drug: Ifosfamide; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: PEG asparaginase; Drug: Prednisone; Drug: Prednisolone; Drug: Thioguanine; Drug: Vincristine; Drug: Vindesine	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 683 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LBL 2018 - International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma
• Actual Study Start Date: August 23, 2019
• Estimated Primary Completion Date: November 22, 2027
• Estimated Study Completion Date: November 22, 2027

Arms and Interventions

Arm	Intervention/treatment
SR I/II: R1 into protocol Ia-Pred; cytoreductive prephase with prednisone; standard induction phase (protocol Ia-prednisone); consolidation phase (protocol Ib); non-HR extra-compartment phase (protocol M); maintenance therapy	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: 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: 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: 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)
Experimental: SR I/II: R1 into protocol Ia-Dexa; cytoreductive prephase with prednisone; experimental induction phase (protocol Ia-dexamethasone); consolidation phase (protocol Ib); non-HR extra-compartment Phase (protocol M); maintenance therapy	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: 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: 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)
SR: R1 into protocol Ia-Pred; cytoreductive prephase with prednisone; standard induction phase (protocol Ia-prednisone); consolidation phase (protocol Ib); non-HR extra-compartment phase (protocol M); reintensification phase (protocol II); maintenance therapy	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: 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)
Experimental: SR: R1 into protocol Ia-Dexa; cytoreductive prephase with prednisone; experimental induction phase (protocol Ia-dexamethasone); consolidation phase (protocol Ib); non-HR extra-compartment phase (protocol M); reintensification phase (protocol II); maintenance therapy	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: 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)
HR: R1 into "Pred" and R2 into non-HR extra-compartment phase; cytoreductive prephase with prednisone; standard induction phase (protocol Ia-prednisone); consolidation phase (protocol Ib); non-HR extra-compartment phase (protocol M); reintensification phase (protocol II); maintenance therapy	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: 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)
Experimental: HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase; cytoreductive prephase with prednisone; experimental induction phase (protocol Ia-dexamethasone); consolidation phase (protocol Ib); non-HR extra-compartment phase (protocol M); reintensification phase (protocol II); maintenance therapy	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: 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)
Experimental: HR: R1 into "Pred" and R2 into HR extra-compartment phase; cytoreductive prephase with prednisone; standard induction phase (protocol Ia-prednisone); consolidation phase (protocol Ib*); HR extra-compartment phase (intensified protocol M); reintensification phase (protocol II); maintenance therapy	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)
Experimental: HR: R1 into "Dexa" and R2 into HR extra-compartment phase; cytoreductive prephase with prednisone; experimental induction phase (protocol Ia-dexamethasone); consolidation phase (protocol Ib*); HR extra-compartment phase (intensified protocol M); reintensification phase (protocol II); maintenance therapy	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)

Outcome Measures

Primary Outcome Measures :

1. Cumulative incidence of relapse with involvement of the CNS (CNS-relapse, pCICR) [ Time Frame: 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.
2. Estimated probability of event-free survival (pEFS) [ Time Frame: 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 :

1. Survival (pOS) [ Time Frame: 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
2. Frequency of treatment-related toxicity overall and in specific protocol elements, randomized arms and during follow up [ Time Frame: through study completion, maximal 7.25 years ]
3. Frequency of treatment-related mortality overall and in specific protocol elements, randomized arms and during follow up [ Time Frame: through study completion, maximal 7.25 years ]
4. Frequency of adverse events of interest and severe adverse events overall [ Time Frame: through study completion, maximal 7.25 years ]
5. Rate of evaluable patients for risk group stratification [ Time Frame: during recruitment ]
6. Cumulative incidence of relapses in association with molecular markers [ Time Frame: through study completion, maximal 7.25 years ]
7. Cumulative incidence of relapses in association with minimal residual disease results [ Time Frame: through study completion, maximal 7.25 years ]

Eligibility Criteria

• Ages Eligible for Study: up to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• newly diagnosed lymphoblastic lymphoma
• age <18 years
• patient enrolled in a participating center
• written informed consent of patient (>14 years of age or according to local law and regulation) and parents to trial participation and transfer and processing of data
• willingness of patients and the investigator/pathologist to provide adequate slides/blocks for reference (molecular) pathology and international pathology panel and/or fresh or fresh frozen samples for genetic risk group stratification if these samples are available after standard diagnostic procedures.

Exclusion criteria:

• lymphoblastic lymphoma as secondary malignancy

• non-lymphoma related relevant medical, psychiatric or social conditions incompatible with trial treatment, including among others

  • prior organ transplant
  • severe immunodeficiency
  • demyelinating Charcot-Marie Tooth syndrome
  • serious acute or chronic infections, such as HIV, VZV and tuberculosis
  • urinary tract infection, cystitis, urinary outflow obstruction, severe renal impairment (creatinine clearance less than 20 ml/min)
  • severe hepatic impairment (bilirubin >3 times ULN, transaminases >10 times ULN)
  • myocardial insufficiency, severe arrhythmias
  • ulcers of the oral cavity and known active gastrointestinal ulcer disease
  • known hypersensitivity to any IMP and to any excipient (listed in section 6.1 of the respective SmPC)
• steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis
• vaccination with live vaccines within 2 weeks before start of protocol treatment
• treatment started according to another protocol or pre-treatment with cytostatic drugs
• participation in another clinical trial that interferes with the protocol, except NHL-BFM Registry 2012 and trials with different endpoints, involving aspects of supportive treatment, which can run parallel to LBL 2018 without influencing the outcome of this trial (e.g. trials on antiemetics, antibiotics, strategies for psychosocial support)
• evidence of pregnancy or lactation period
• sexually active adolescents not willing to use highly effective contraceptive method (pearl index < 1) until 12 months after end of cytostatic therapy

Contacts and Locations

Contacts

Contact: Birgit Burkhardt, Prof. Dr. Dr.; +49 251 83 55696; LBL2018@ukmuenster.de

Locations

Austria

Univ.Klinik für Kinder- und Jugendheilkunde Graz, Klin. Abteilung für pädiatrische Hämato-Onkologie; Recruiting

Graz, Austria, 8036

Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck, Universitätsklinik für Pädiatrie I; Recruiting

Innsbruck, Austria, 6020

Kepler Universitätsklinikum, Med Campus IV / Onkologie; Recruiting

Linz, Austria, 4020

LKH Salzburg, Universitätsklinik für Kinder- und Jugendheilkunde, Kinderonkologie; Recruiting

Salzburg, Austria, 5020

St. Anna Kinderspital; Recruiting

Wien, Austria, 1090

Belgium

Hôpital Universitaire des Enfants Reine Fabiola (ULB), Pédiatrie hémato-oncologie; Recruiting

Brussels, Belgium, 1020

University Hospital Brussels, Pediatrische oncologie; Recruiting

Brussel, Belgium, 1090

Cliniques Universitaires Saint-Luc (UCL), Hématologie et oncologie pédiatrique; Recruiting

Brussel, Belgium, 1200

UZ Antwerpen Kinderhemato-oncologie; Recruiting

Edegem, Belgium, 2650

University Hospital Gent Pediatrische hemato-oncologie; Recruiting

Gent, Belgium, 9000

University Hospitals Leuven, Kinderhemato-oncologie; Recruiting

Leuven, Belgium, 3000

CHR Citadelle Hémato - oncologie pédiatrique; Recruiting

Liège, Belgium, 4000

CHR Citadelle Hémato - oncologie pédiatrique; Recruiting

Montegnée, Belgium, 4000

China

Hong Kong Children's Hospital; Not yet recruiting

Hong Kong, China

Czechia

Dept. of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University Cernopolni; Recruiting

Brno, Czechia, 662 63

Dept. of Pediatric Hematology and Oncology. University Hospital Motol and 2nd Medical School, Charles University; Recruiting

Praha, Czechia, 160 06

Denmark

University Hospital Aalborg, Nord, Department of Pediatrics; Recruiting

Aalborg, Denmark, 9000

Aarhus University Hospital, Department of Pediatrics; Recruiting

Aarhus, Denmark, 8200

Børneonkologisk afsnit 5054, BørneUngeKlinikken, Juliane Marie Centret, Rigshospitalet; Recruiting

Kobenhavn, Denmark, 2100 Ø

H.C. Andersens Children Hospital, Odense University Hospital; Recruiting

Odense, Denmark, 5000

Finland

Helsinki University Hospital, Department of Pediatric Hematology and Oncology; Recruiting

Helsinki, Finland, 00029 HUS

Kuopio University Hospital, Department of Pediatric Hematology and Oncology; Recruiting

Kuopio, Finland, 70029 KYS

University Hospital of Oulu, Paediatric Haematology and Oncology; Recruiting

Oulu, Finland, 90029 OYS

Tampere University Hospital, Paediatric Haematology and Oncology; Recruiting

Tampere, Finland, 33521 Tampere

Turku University Hospital, Paediatric and Adolescent Haematology and Oncology; Recruiting

Turku, Finland, 20521 Turku

France

Service d'oncolologie, Hématologie pédiatrique. CHU Amiens, Avenue René Laënnec - SALOUEL; Not yet recruiting

Amiens, France, 80054

Pôle Femme Mère Enfant ; Unité d'Hématologie/Oncologie pédiatrique, CHU Angers; Not yet recruiting

Angers, France, 49033

Hématologie Oncologie pédiatrique, CHRU Besançon; Not yet recruiting

Besançon, France, 25030

Hôpital de Enfants, Unité Onco-Hématologie Pédiatrique, Groupe Hospitalier Pellegrin; Not yet recruiting

Bordeaux, France, 33076

Département de Pédiatrie et Génétique Médicale CHRU Morvan; Not yet recruiting

Brest, France, 29609

Unité d'hémato-immuno-oncologie pédiatrique. Centre Hospitalier Universitaire niveau 1 - bâtiment FEH; Not yet recruiting

Caen, France, 14033

Unité Onco- Hématologie Pédiatrique CHU Estaing 1 place Lucie-Aubrac; Not yet recruiting

Clermont-Ferrand, France, 63303

Service Immuno-Hématologie Oncologie Pédiatrique; Not yet recruiting

Dijon, France, 21079

Service onco hématologie pédiatrique CHU de Grenoble site Nord - Hôpital Couple enfant; Not yet recruiting

Grenoble, France, 38043

Unité d'hématologie pédiatrique CHRU de Lille - Hôpital Jeanne de Flandre; Not yet recruiting

Lille, France, 59037

Service d'Hématologie - Oncologie pédiatrique CHU Limoges - Hôpital de la mère et de l'enfant; Not yet recruiting

Limoges, France, 87042

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; Not yet recruiting

Lyon, France, 69373

Service de Pédiatrie et hématologie pédiatrique, CHU de Marseille - Hôpital de la Timone; Not yet recruiting

Marseille, France, 13385

UAM Hématologie et Oncologie Pédiatrique, CHU de Montpellier - Hôpital Arnaud de Villeneuve; Not yet recruiting

Montpellier, France, 34295

Service d'hématologie et oncologie pédiatriques, Hôpital enfant-adolescent, CHU NANTES; Not yet recruiting

Nantes, France, 44093

Service d'hémato-oncologie pédiatrique CHU NICE - Hôpital l'Archet 2; Not yet recruiting

Nice, France, 06200

service d'oncologie pédiatrique, institut Curie; Not yet recruiting

Paris, France, 75005

Service Hémato-immuno- oncologie- CHU PARIS Armand Trousseau; Not yet recruiting

Paris, France, 75012

Service d' hémato-immunologie CHU Paris - Hôpital Robert Debré; Not yet recruiting

Paris, France, 75019

Service Oncologie-Hématologie pédiatrique CHU de Poitiers; Not yet recruiting

Poitiers, France, 86000

Service d'Hémato-Oncologie Pédiatrique- American Hospital; Not yet recruiting

Reims, France, 51100

Pôle pédiatrie Hémato-cancérologie pédiatrique- CHU RENNES - Hôpital sud; Not yet recruiting

Rennes, France, 35203

Service d'Hemato-Oncologie Pediatrique CHU Rouen; Not yet recruiting

Rouen, France, 76031

service d'oncologie pédiatrique, hopital Félix Guyon; Not yet recruiting

Saint-Denis, France, 97405

Pôle mère enfant-Unité Hématologie - Oncologie pédiatrique - CHU Hôpital NORD; Not yet recruiting

Saint-Priest-en-Jarez, France, 42270

Service d'Onco-Hematologie Pediatrique CHU STRASBOURG -Hôpital de Hautepierre; Not yet recruiting

Strasbourg, France, 67098

Service Pédiatrie - Hématologie Immunologie Oncologie - CHU Toulouse; Not yet recruiting

Toulouse, France, 31059

Service d'hémato-oncologie pédiatrique- CHU de Nancy - Hôpital de Brabois Enfant; Not yet recruiting

Vandœuvre-lès-Nancy, France, 54511

Dépt de Pédiatrie Gustave Roussy; Not yet recruiting

Villejuif, France, 94805

Germany

Universitätsklinikum Aachen .Klinik für Kinder - und Jugendmedizin Hämatologie / Onkologie; Recruiting

Aachen, Germany, 52057

Klinikum Augsburg ,Schwäbisches Kinderkrebszentrum. I. Klinik für Kinder und Jugendliche Hämatologie / Onkologie; Recruiting

Augsburg, Germany, 86156

HELIOS Klinikum Berlin-Buch, Kinderklinik, Pädiatrische Hämatologie und Onkologie; Recruiting

Berlin, Germany, 13125

Charité Campus Virchow-Klinikum, Zentrum für Kinder- und Jugendmedizin- Abt. Hämatologie / Onkologie; Recruiting

Berlin, Germany, 13353

Evangelisches Krankenhaus Bielefeld GmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie; Recruiting

Bielefeld, Germany, 33617

Zentrum für Kinderheilkunde der Universität Bonn, Abt. Päd. Hämatologie / Onkologie; Recruiting

Bonn, Germany, 55113

Städtisches Klinikum Braunschweig gGmbH, Zentrum für Kinder- und Jugendmedizin; Recruiting

Braunschweig, Germany, 38126

Klinikum Bremen-Mitte gGmbH, Prof.-Hess-Kinderklinik,Pädiatrische Onkologie und Hämatologie; Recruiting

Bremen, Germany, 28177

Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie; Not yet recruiting

Chemnitz, Germany, 09116

Carl-Thiem-Klinikum, Kinderklinik, Station 5e; Recruiting

Cottbus, Germany, 03048

Vestische Kinderklinik, Universität Witten / Herdecke; Recruiting

Datteln, Germany, 45711

Klinikum Dortmund gGmbH, Klinik für Kinder- und Jugendmedizin, Station K1, Abt. Päd. Onkologie / Hämatologie; Recruiting

Dortmund, Germany, 44137

Universitätsklinik Carl Gustav Carus der TU Dresden, Klinik für Kinder- und Jugendmedizin; Recruiting

Dresden, Germany, 01307

Universitätsklinikum Düsseldorf, Zentrum für Kinder- und Jugendmedizin, Klinik für Päd. Hämatologie und Onkologie; Recruiting

Düsseldorf, Germany, 40225

HELIOS Klinikum Erfurt GmbH, Klinik für Kinder- und Jugendmedizin, Päd. Onkologie / Hämatologie; Recruiting

Erfurt, Germany, 99089

Universitätsklinikum Erlangen, Klinik für Kinder- und Jugendmedizin, Pädiatrische Onkologie / Hämatologie; Recruiting

Erlangen, Germany, 91054

Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin, Hämatologie / Onkologie; Recruiting

Essen, Germany, 45122

Universitätsklinikum Frankfurt, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie; Recruiting

Frankfurt, Germany, 60590

Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie; Recruiting

Freiburg, Germany, 79106

Universitätsklinikum Gießen und Marburg, Standort Gießen, Zentrum für Kinderhämatologie und -onkologie; Recruiting

Gießen, Germany, 35385

Universitätsklinikum Greifswald KdöR, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Onkologie und Hämatologie; Recruiting

Greifswald, Germany, 17475

Georg-August-Universität Universitäts-Kinderklinik, Pädiatrie I; Recruiting

Göttingen, Germany, 37075

Universitätsklinikum Halle (Saale), Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie; Recruiting

Halle, Germany, 06120

Universitätsklinikum Hamburg Eppendorf, Zentrum für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie; Recruiting

Hamburg, Germany, 20246

Medizinische Hochschule Hannover, Kinderheilkunde, Päd. Hämatologie / Onkologie; Recruiting

Hannover, Germany, 30625

Universitäts-Kinderklinik Heidelberg, Abt. Hämatologie / Onkologie; Recruiting

Heidelberg, Germany, 69120

Gemeinschaftskrankenhaus Herdecke, Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie; Recruiting

Herdecke, Germany, 58313

Universitätskliniken für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie, Geb. 9; Recruiting

Homburg, Germany, 66421

Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin; Recruiting

Jena, Germany, 07745

Städtisches Klinikum Karlsruhe gGmbH, Kinderklinik, Station S 24; Recruiting

Karlsruhe, Germany, 76133

Klinikum Kassel Gesundheit Nordhessen Holding AG, Klinik für pädiatrische Hämatologie und Onkologie; Recruiting

Kassel, Germany, 34125

Universitätsklinikum Schleswig Holstein Campus Kiel, Klinik für Allgemeine Pädiatrie, Päd. Onkologie / Hämatologie; Recruiting

Kiel, Germany, 24105

Gemeinschaftsklinikum Mittelrhein Kemperhof, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie; Recruiting

Koblenz, Germany, 56073

HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Päd. Hämatologie/Onkologie; Recruiting

Krefeld, Germany, 47805

Klinikum der Universität zu Köln, Klinik für Kinder- und Jugendmedizin, Abt. Kinderonkologie und -hämatologie; Not yet recruiting

Köln, Germany, 50924

Universitätsklinikum Leipzig, Klinik für Kinder und Jugendliche, Abt. Päd. Hämatologie / Onkologie; Recruiting

Leipzig, Germany, 04103

Universitätsklinikum Schleswig Holstein Campus Lübeck, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie; Recruiting

Lübeck, Germany, 23538

Universitätsklinikum Magdeburg A. ö. R., Kinderklinik, Päd. Hämatologie / Onkologie; Recruiting

Magdeburg, Germany, 39120

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie; Recruiting

Mainz, Germany, 55101

Klinikum Mannheim gGmbH, Universitäts-Kinderklinik, Päd. Onkologie /Hämatologie; Recruiting

Manheim, Germany, 68167

Johannes Wesling Klinikum Minden, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie, Station E 22; Recruiting

Minden, Germany, 32429

Klinikum der LMU, Dr. von Haunersches Kinderspital, Pädiatrische Hämatologie / Onkologie; Recruiting

München, Germany, 80337

Klinikum Schwabing, Kinderklinik der TU Päd. Hämatologie / Onkologie, Station 24d; Recruiting

München, Germany, 80804

Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie; Recruiting

Münster, Germany, 48149

Diakonie Neuendettelsau, Kliniken Hallerwiese / Cnopf'sche Kinderklinik, Pädiatrische Hämatologie /Onkologie; Recruiting

Nürnberg, Germany, 90419

Klinikum Oldenburg AöR, Zentrum für Kinder- und Jugendmedizin, Abt. Hämatologie / Onkologie; Recruiting

Oldenburg, Germany, 26133

Universitätsklinikum Regensburg, Klinik für Kinder- und Jugendmedizin, Abt. Päd. Hämatologie, Onkologie, SZT; Recruiting

Regensburg, Germany, 93053

Universitätsklinikum Rostock, Kinder- und Jugendklinik, Päd. Hämatologie und Onkologie; Recruiting

Rostock, Germany, 18057

Asklepios Klinik St. Augustin GmbH, Kinder- und Jugendmedizin, Kinder-Hämatologie und Onkologie; Recruiting

Sankt Augustin, Germany, 53757

HELIOS Kliniken Schwerin GmbH, Klinik für Kinder- und Jugendmedizin, Station A1; Recruiting

Schwerin, Germany, 19049

Klinikum Stuttgart, Olgahospital Zentrum für Kinder- und Jugendmedizin Pädiatrie 5 (Onkologie, Hämatologie, Immunologie); Recruiting

Stuttgart, Germany, 70174

Klinikum Mutterhaus der Borromäerinnen gGmbH, Pädiatrische Abteilung; Withdrawn

Trier, Germany, 54290

Universitätsklinik Tübingen, Klinik für Kinderheilkunde und Jugendmedizin, Päd. Hämatologie / Onkologie; Recruiting

Tübingen, Germany, 72076

Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie; Recruiting

Ulm, Germany, 89081

Universitätskinderklinik Würzburg, Päd. Onkologie und Hämatologie; Recruiting

Würzburg, Germany, 97080

Hungary

2nd Dep. of Pediatrics, Semmelweis Univ; Not yet recruiting

Budapest, Hungary

Heim Pal Children Hospital; Not yet recruiting

Budapest, Hungary

Dep. of Pediatrics, Univ. of Debrecen; Not yet recruiting

Debrecen, Hungary

Children's Treating Center, Miskolc; Not yet recruiting

Miskolc, Hungary

Dep. of Pediatrics, University of Pecs; Not yet recruiting

Pécs, Hungary

Dep. of Pediatrics, Univ. of Szeged; Not yet recruiting

Szeged, Hungary

Ireland

Our Lady's Children's Hospital Crumlin; Not yet recruiting

Dublin, Ireland

Israel

Children's Hospital at Soroka Medical Center; Not yet recruiting

Be'er Sheva, Israel

Ruth Rappaport Children's Hospital, Rambam Medical Center; Not yet recruiting

Haifa, Israel

Children's Hospital at Hadassah, Ein Kerem Medical Center; Not yet recruiting

Jerusalem, Israel

Schneider Children's hospital, Rabin Medical Center; Not yet recruiting

Petah tikva, Israel

Edmond and Lily Safra Children's Hospital, Sheba Medical Center; Not yet recruiting

Ramat Gan, Israel

Dana Children's Hospital, Tel-Aviv Sourasky Medical Center; Not yet recruiting

Tel Aviv, Israel

Italy

Clinica Pediatrica, Centro Regionale Oncoematologia Pediatrica- Ospedale dei Bambini "G. Salesi"; Not yet recruiting

Ancona, Italy, 60123

Dipartimento Biomedicina Età Evolutiva- U.O. Pediatrica I Policlinico; Not yet recruiting

Bari, Italy, 70124

Dipartimento Pediatrico degli OO.RR. di Bergamo; Not yet recruiting

Bergamo, Italy, 24100

Dipartimento di Scienze Pediatriche Mediche Chirurgiche Ospedale Sant'Orsola Malpighi; Not yet recruiting

Bologna, Italy, 40138

Clinica Pediatrica Ospedale Civile; Not yet recruiting

Brescia, Italy, 25123

Istituto di Clinica Pediatrica- Ospedale Regionale Microcitemie; Not yet recruiting

Cagliari, Italy, 09121

Divisione Ematologia - Oncologia Pediatrica, Clinica Pediatrica; Not yet recruiting

Catania, Italy, 95123

U. O. di Pediatria- Azienda Ospedaliera Annunziata; Not yet recruiting

Cosenza, Italy, 87100

Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria - Università di Ferrara; Not yet recruiting

Ferrara, Italy, 44100

Unità Autonoma di Oncoematologia Pediatrica, Dipartimento Pediatria - Azienda "A.Meyer"; Not yet recruiting

Firenze, Italy, 50132

Dipartimento di Ematologia e Oncologia Pediatrica Istituto " G. Gaslini"; Not yet recruiting

Genova, Italy, 16148

Divisione di Oncologia Pediatrica Ist. Nazionale Studio e Cura Tumori; Not yet recruiting

Milano, Italy, 20133

U.O. di Ematologia, Oncologia e Trapianto-Azienda Policlinico di Modena; Not yet recruiting

Modena, Italy, 41100

Clinica Pediatrica Ospedale S. Gerardo Via Donizetti; Not yet recruiting

Monza, Italy, 20052

S.C. Ematologia Oncologica- Ospedale "Pausilipon"; Not yet recruiting

Napoli, Italy, 80123

Clinica di Oncoematologia Pediatrica- Azienda Ospedaliera-Università di Padova; Not yet recruiting

Padova, Italy, 35128

Oncoematologia Pediatrica- Ospedale dei Bambini G. di Cristina; Not yet recruiting

Palermo, Italy, 90100

U.O. di Pediatria e Oncoematologia Pediatrica. Az. Osp. di Parma; Not yet recruiting

Parma, Italy, 43100

Oncoematologia Pediatrica IRCCS, Policlinico San Matteo Piazzale Golgi; Not yet recruiting

Pavia, Italy, 27100

Dipartimento di Ematologia -Ospedale Civile; Not yet recruiting

Pescara, Italy, 65123

U.O. Pediatria Ospedale Infermi- Azienda USL Rimini; Not yet recruiting

Rimini, Italy, 47900

Sezione Ematologia- Dipart. Biotecnico Cellulare ed Ematologia- Università "La Sapienza"; Not yet recruiting

Roma, Italy, 00161

Divisione di Ematologia Pediatrica- Ospedale "Bambino Gesù". Istituto di Ricerca Scientifica; Not yet recruiting

Roma, Italy, 00165

Divisione di Pediatria- Ospedale "Casa Sollievo della Sofferenza"; Not yet recruiting

San Giovanni Rotondo, Italy, 71013

Oncologia Pediatrica,- Ospedale "R. Silvestrini"; Not yet recruiting

San Sisto, Italy, 06080

Dip. Scienze Pediatriche e dell'Adolescenza Ospedale Infantile Regina Margherita; Not yet recruiting

Torino, Italy, 10126

U.O. Emato-Oncologia Pediatrica- Università degli studi di Trieste-Ospedale Infantile Burlo Garofolo; Not yet recruiting

Trieste, Italy, 34137

U.O. Oncoematologia Pediatrica- Policlinico "G.B. Rossi"; Not yet recruiting

Verona, Italy, 37134

Netherlands

Princess Maxima Centre for Pediatric Oncology; Not yet recruiting

Utrecht, Netherlands, 3584CS

Norway

Haukeland University Hospital in Bergen; Recruiting

Bergen, Norway

University Hospital Northern Norway; Recruiting

Tromsø, Norway

St Olavs Hospital in Trondheim; Recruiting

Trondheim, Norway

Poland

Department of Pediatric Oncology and Hematology, Medical University of Bialystok; Not yet recruiting

Białystok, Poland, 15-247

Department of Pediatric Hematology and Oncology, Nicolaus Copernicus University; Not yet recruiting

Bydgoszcz, Poland, 85-094

Department of Pediatric Hematology and Oncology, Center of Pediatrics and Oncology in Chorzów; Not yet recruiting

Chorzów, Poland, 41-500

Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdansk; Not yet recruiting

Gdańsk, Poland, 20-211

Department of Pediatric Oncology and Hematology, Center of Pediatrics in Kielce; Not yet recruiting

Kielce, Poland, 25-736

Department of Pediatric Oncology/Hematology, Institute of Pediatrics, Medical College Jagiellonian University; Not yet recruiting

Kraków, Poland, 30-663

Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin; Not yet recruiting

Lublin, Poland, 20-093

Department of Pediatric Oncology and Hematology, Provincial Specialist Children's Hospital; Not yet recruiting

Olsztyn, Poland, 10-561

Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences; Not yet recruiting

Poznań, Poland, 60-572

Department of Paediatric Oncology and Haematology, University of Rzeszów, Department of Pediatrics; Not yet recruiting

Rzeszów, Poland, 35-301

Department of Pediatrics, Children Hematology nad Oncology, Pomeranian Medical University; Not yet recruiting

Szczecin, Poland, 71-242

Department of Pediatrics, Hematology and Oncology, Medical University of Warsaw; Not yet recruiting

Warsaw, Poland, 00-576

Department of Pediatric Oncology, Children's Memorial Health Institute; Not yet recruiting

Warsaw, Poland, 04-576

Department of Bone Marrow Transplantation, Children Oncology and Hematology, Wroclaw Medical University; Not yet recruiting

Wrocław, Poland, 50-556

Department of Pediatric Hematology and Oncology, Silesian Medical University in Katowice; Not yet recruiting

Zabrze, Poland, 41-800

Department of Pediatrics, Oncology, Hematology and Diabetology, Institute of Pediatrics, Medical University of Lodz; Not yet recruiting

Łódź, Poland, 91-138

Portugal

Centro Hospitalar e Universitário de Coimbra; Not yet recruiting

Coimbra, Portugal, 3000-602

Instituto Português de Oncologia - Francisco Gentil - Libosa; Not yet recruiting

Lisboa, Portugal, 1099-023

Instituto Português de Oncologia - Francisco Gentil - Porto; Not yet recruiting

Porto, Portugal, 4200-072

Russian Federation

Oncological center of regional Children's Hospital; Recruiting

Ekaterinburg, Russian Federation

National Center for Pediatric Hematology, Oncology and Immunology Moscow; Recruiting

Moscow, Russian Federation, 117198

Slovakia

Department of pediatric oncology and hematology, Children´s Faculty Hospital; Not yet recruiting

Banská Bystrica, Slovakia, 974 09

Department of pediatric hematology and oncology, National Institute of Children's Diseases; Not yet recruiting

Bratislava, Slovakia, 833 40

Department of pediatric hematology and oncology, Children´s University Hospital; Not yet recruiting

Košice, Slovakia, 04011

Spain

Hospital General Universitario de Alicante; Recruiting

Alicante, Spain, 03010

Hospital Universitario Torrecárdenas; Recruiting

Almería, Spain, 04009

Hospital Materno-Infantil de Badajoz; Recruiting

Badajoz, Spain, 06010

Hospital Universitario Cruces; Recruiting

Baracaldo, Spain, 48903

Hospital Universitari Vall d'Hebron; Recruiting

Barcelona, Spain, 08035

Hospital de la Santa Creu i Sant Pau; Recruiting

Barcelona, Spain, 08041

Hospital Universitario Donostia; Recruiting

Donostia, Spain, 20014

Hospital Sant Joan de Déu; Recruiting

Esplugues De Llobregat, Spain, 08950

Hospital Universitario Virgen de las Nieves; Recruiting

Granada, Spain, 18014

Complejo Hospitalario Universitario Insular Materno Infantil; Recruiting

Las Palmas De Gran Canaria, Spain, 35016

Hospital General Universitario Gregorio Marañón; Recruiting

Madrid, Spain, 28007

Hospital Infantil Universitario Niño Jesús; Recruiting

Madrid, Spain, 28009

Hospital Universitario 12 de Octubre; Recruiting

Madrid, Spain, 28041

Hospital Universitario La Paz; Recruiting

Madrid, Spain, 28046

Hospital Clínico Universitario Virgen de la Arrixaca; Recruiting

Murcia, Spain, 30120

Hospital Regional Universitario de Málaga; Recruiting

Málaga, Spain, 29010

Hospital Universitario Central de Asturias; Recruiting

Oviedo, Spain, 33011

Hospital Universitari Son Espases; Recruiting

Palma De Mallorca, Spain, 07120

Hospital Virgen del Camino; Recruiting

Pamplona, Spain, 31008

Complejo Hospitalario Universitario de Vigo; Recruiting

Pontevedra, Spain, 36036

Hospital Universitario Nuestra Señora de Candelaria; Recruiting

Santa Cruz De Tenerife, Spain, 38010

Hospital Universitario Marqués de Valdecilla; Recruiting

Santander, Spain, 390008

Hospital Clínico Universitario de Santiago; Recruiting

Santiago De Compostela, Spain, 15706

Hospital Universitario Virgen Macarena; Recruiting

Sevilla, Spain, 41009

Hospital Universitario Virgen del Rocío; Recruiting

Sevilla, Spain, 41013

Hospital Virgen de la Salud; Recruiting

Toledo, Spain, 45004

Hospital Clínico Universitario de Valencia; Recruiting

Valencia, Spain, 46010

Hospital Universitari i Politècnic La Fe; Recruiting

Valencia, Spain, 46026

Hospital Clínico Universitario de Valladolid; Recruiting

Valladolid, Spain, 47003

Hospital Universitario Miguel Servet; Recruiting

Zaragoza, Spain, 50009

Sweden

Barncancercentrum, Drottning Silvias Barn och Ungdomssjukhus, Sahlgrenska Universitetssjukhuset; Recruiting

Göteborg, Sweden, 416 85

Barnonkologiska enheten, Barn och Ungdomsmedicinska kliniken, Universitetssjukhuset i Linköping; Recruiting

Linköping, Sweden, 581 85

Barnonkologi, Skåne Universitetssjukhus; Recruiting

Lund, Sweden, 221 85

Barncanceravdelningen Astrid Lindgrens Barnsjukhus, Nya Karolinska Universitetssjukhuset; Recruiting

Stockholm, Sweden, 171 76

Barnonkologiska avdelningen, Barn 3, Norrlands Universitetssjukhus; Recruiting

Umeå, Sweden, 901 85

Barnavdelningen för blod- och tumörsjukdomar 95A, Akademiska sjukhuset; Recruiting

Uppsala, Sweden, 752 39

Switzerland

Kantonsspital Aarau; Not yet recruiting

Aarau, Switzerland, 5001

Universitäts-Kinderspital beider Basel (UKBB); Not yet recruiting

Basel, Switzerland, 4056

Ospedale San Giovanni; Not yet recruiting

Bellinzona, Switzerland, 6500

Inselspital Bern, University of Bern; Not yet recruiting

Bern, Switzerland, 3010

HUG Hôpitaux Universitaires de Genève; Not yet recruiting

Geneva, Switzerland, 1211

CHUV - Centre Hospitalier Universitaire Vaudois; Not yet recruiting

Lausanne, Switzerland, 1011

Luzerner Kantonspital - Kinderspital Luzern; Not yet recruiting

Luzern, Switzerland, 6000

Ostschweizer Kinderspital; Not yet recruiting

Sankt Gallen, Switzerland, 9006

Universitäts-Kinderspital Zürich; Not yet recruiting

Zürich, Switzerland, 8032

Sponsors and Collaborators

University Hospital Muenster

Deutsche Krebshilfe e.V., Bonn (Germany)

Investigators

• Principal Investigator: Birgit Burkhardt, Prof. Dr. Dr.; University Hospital Muenster, Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Khanam T, Sandmann S, Seggewiss J, Ruether C, Zimmermann M, Norvil AB, Bartenhagen C, Randau G, Mueller S, Herbrueggen H, Hoffmann P, Herms S, Wei L, Woeste M, Wuensch C, Gowher H, Oschlies I, Klapper W, Woessmann W, Dugas M, Burkhardt B. Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance. Blood. 2021 Apr 29;137(17):2347-2359. doi: 10.1182/blood.2020005381.

• Responsible Party: University Hospital Muenster
• ClinicalTrials.gov Identifier: NCT04043494
• Other Study ID Numbers: UKM17_0023; 2017-001691-39 ( EudraCT Number )
• First Posted: August 2, 2019
• Last Update Posted: December 16, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Cytarabine; Dexamethasone; Prednisone; Prednisolone; Cyclophosphamide; Ifosfamide; Doxorubicin; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Thioguanine; Pegaspargase; Vindesine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents