International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma (LBL 2018)
Brief Summary
- 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
- 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)
Intervention / Treatment
Study Design
Treatment
Randomized
Parallel Assignment
None (Open Label)
Arm Groups
Other: SR I/II: R1 into protocol Ia-Pred
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
Experimental: SR I/II: R1 into protocol Ia-Dexa
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
Other: SR: R1 into protocol Ia-Pred
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
Experimental: SR: R1 into protocol Ia-Dexa
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
Other: HR: R1 into "Pred" and R2 into non-HR extra-compartment phase
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
Experimental: HR: R1 into "Dexa" and R2 into non-HR extra-compartment phase
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
Experimental: HR: R1 into "Pred" and R2 into HR extra-compartment phase
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
Experimental: HR: R1 into "Dexa" and R2 into HR extra-compartment phase
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
Eligibility 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.
- 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
Outcome Measures
Cumulative incidence of relapse with involvement of the CNS (CNS-relapse, pCICR)
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.
Through study completion, maximal 7.25 years
Estimated probability of event-free survival (pEFS)
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.
Through study completion, maximal 7.25 years
Survival (pOS)
Survival (pOS) is defined as time from diagnosis to death due to any cause or to the date of last contact for patients alive
Through study completion, maximal 7.25 years
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
Rate of evaluable patients for risk group stratification
During recruitment
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
Where is this study conducted?
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