Lymphoblastic lymphoma MedDRA version: 20.0 Level: LLT Classification code 10065923 Term: Lymphoblastic lymphoma System Organ Class: 100000004864
Conditions
Sponsors
University Hospital Münster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting the following criteria are eligible to the study (inclusion criteria): •newly diagnosed lymphoblastic lymphoma •age 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 Are the trial subjects under 18? yes Number of subjects for this age range: 683 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients meeting the following criteria are not eligible to the study (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 •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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the first randomized question (R1) open for all LBL patients (pts) of the core study cohort, is to evaluate whether the cumulative incidence of relapses in the central nervous system can be decreased by substituting prednisone (60 mg/m²/d for 21 days plus a 9 day tapering) (standard arm, SA) by dexamethasone (10 mg/m²/d for 14 days without tapering) (experimental arm, EA) in induction therapy. The primary objective of the second randomized question (R2) open for high-risk pts of the core study cohort, is to test whether the probability of pEFS can be improved by an intensified treatment arm (EA) compared to the standard treatment arm (SA). In the EA pts receive 2 additional doses of PEG asparaginase during protocol Ib* and an intensified protocol M consisting of one course for high-risk (HR) ALL (HR-1’), followed by one standard high-dose methotrexate (MTX) course, followed by another intense course for HR ALL (HR-2’) and a second standard high-dose MTX course.;Secondary Objective: Here we aim to analyze: •the pEFS and cumulative incidence of relapse/CNS-relapse as compared to study EURO-LB 02 •overall survival (pOS) defined as time from diagnosis to death of any cause or to date of last contact for patients alive as compared to study EURO-LB 02 •treatment related mortality in the randomized arms and compared to study EURO-LB 02 •adverse event and severe adverse event profile in specific protocol elements or randomized arms and during follow-up and compared to study EURO-LB 02 •feasibility and results of risk group stratification •feasibility of minimal residual disease evaluation in children and adolescents with LBL •identification of prognostic molecular markers for T-LBL which can be added to the risk group stratification system in a subsequent trial(PTEN mutations and deletions, PIK3CA, PIK3R1, KRAS, NRAS, chromosome 6q alterations, status of TRG locus and further molecular markers identified in the targeted panel of mole | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the trial LBL 2018 are the following •survival (pOS) 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 and mortality overall and in specific protocol elements, randomized arms and during follow-up •frequency of adverse events of interest and severe adverse events overall •rate of evaluable patients for risk group stratification •cumulative incidence of relapses in association with molecular markers of the published genetic classifier in T-LBL patients and molecular markers identified in the targeted panel of molecular markers for T-LBL. •cumulative incidence of relapses in association with minimal residual disease results. ;Timepoint(s) of evaluation of this end point: Final analysis: intended to be performed 3 years after randomization of the last patient | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Netherlands, Norway, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Switzerland
Contacts
Public ContactNHL-BFM study center
Universitätsklinikum Münster
Outcome results
None listed