Primary objectives: - Overall: Improvement of event-free survival (EFS) probabilities in childhood relapsed ALL - Randomization 1: EFS of Arm A (ALL-REZ BFM 2002) versus B (ALLR3) in SR patients - Randomization 2: Influence of…
ID
Source
Brief title
Condition
- Leukaemias
Health condition
IntReALL, Relapsed ALL 2010
Research involving
Sponsors and support
European Union
Intervention
Outcome measures
Primary outcome
Primary parameters:
- Overall: Improvement of event-free survival (EFS) probabilities in childhood relapsed ALL
- Randomization 1: EFS of Arm A (ALL-REZ BFM 2002) versus B (ALLR3) in SR patients
- Randomization 2: Influence of epratuzumab on EFS in consolidation of SR patients
Secondary outcome
Secondary parameters:
- OS of Arm A (ALL-REZ BFM 2002) versus B (ALLR3) in SR patients
- Influence of epratuzumab on OS in consolidation of SR patients
- Rate of second complete remission (CR2) of Arm A versus Arm B
- Rate of SCT performed in Arm A versus Arm B
- Toxicity of randomized SR arms A versus B
- Toxicity of consolidation with versus without epratuzumab
- Improvement of MRD reduction during consolidation with versus without epratuzumab
- Rate of MRD negativity prior to SCT with Arm A vs. Arm B
- Rate of MRD negativity prior to SCT after consolidation with versus without epratuzumab
- Pharmacokinetic of epratuzumab in context with arm A and arm B
Background summary
Within the group, over the last few years two different treatment protocols, ALL-REZ BFM 2002 and ALL R3 have been used by most study groups for treatment of relapsed ALL. Both trials have produced comparable results. The trials risk stratified patients based on duration of first
remission, immunophenotype, site of relapse and post induction minimal residual disease (MRD) levels to identify patients who should be transplanted. For non-HR or standard risk (SR) patients both ALL-REZ BFM 2002 and ALL R3 have achieved better results than previous trials.
Both protocols have however been primarily used in patients relapsing off different frontline protocols. Thus there is need for a prospective randomized controlled comparison across the study groups (randomization 1), before a uniform backbone for further trials can be developed.
[The 2nd randomisation with/without Epratuzumab closed 01-02-2019]
In SR patients, survival may be improved by modifying the consolidation therapy using targeted non-myelotoxic drugs. As ideal candidate, epratuzumab (humanised chimeric anti CD22 antibody) will be randomly tested in combination with conventional chemotherapy (randomization 2). CD22 is well expressed in all B-cell precursor ALL cells. Epratuzumab has been developed in combination phase I and II trials in childhood relapsed ALL and has shown a favourable toxicity profile and moderate antileukemic activity.
Study objective
- Overall: Improvement of event-free survival (EFS) probabilities in childhood relapsed ALL
- Randomization 1: EFS of Arm A (ALL-REZ BFM 2002) versus B (ALLR3) in SR patients
- Randomization 2: Influence of epratuzumab on EFS in consolidation of SR patients
Secondary objectives:
- OS of Arm A (ALL-REZ BFM 2002) versus B (ALLR3) in SR patients
- Influence of epratuzumab on OS in consolidation of SR patients
- Rate of second complete remission (CR2) of Arm A versus Arm B
- Rate of SCT performed in Arm A versus Arm B
- Toxicity of randomized SR arms A versus B
- Toxicity of consolidation with versus without epratuzumab
- Improvement of MRD reduction during consolidation with versus without epratuzumab
- Rate of MRD negativity prior to SCT with Arm A vs. Arm B
- Rate of MRD negativity prior to SCT after consolidation with versus without epratuzumab
- Pharmacokinetic of epratuzumab in context with arm A and arm B
Study design
- SR induction/consolidation arm A (ALL-REZ BFM 2002, arm protocol II-IDA) versus B (UKALL-R3, arm MITOX): prospective, randomized, open label, phase III trial
[The 2nd randomisation with/without Epratuzumab closed 01-02-2019]
- SR consolidation +/- epratuzumab: prospective, randomized, open label, phase III trial
Intervention
| Epratuzumab |
Study burden and risks
Prof. dr. P.M. Hoogerbrugge
Heidelberglaan 25
3584 CS
Utrecht
Nederland
088 972 72 72
trialmanagement@prinsesmaximacentrum.nl
Prof. Dr. P.M. Hoogerbrugge
Heidelberglaan 25
3584 CS
Utrecht
Nederland
088 972 72 72
trialmanagement@prinsesmaximacentrum.nl
Age
Inclusion criteria
• Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL
• Children less than 18 years of age at inclusion
• Meeting SR criteria: late isolated or late/early combined BCP BM relapse, any late/early isolated extramedullary relapse
• Patient enrolled in a participating centre
• Written informed consent
• Start of treatment falling into the study period
• No participation in other clinical trials 30 days prior to study enrolment that interfere with this protocol, except trials for primary ALL Inclusion criteria specific for the epratuzumab randomization
• Precursor B-cell immunophenotype. A specific CD22 expression level is not required
• M1 or M2 status of the bone marrow after induction
Exclusion criteria
• BCR-ABL / t(9;22) positive ALL
• Pregnancy or positive pregnancy test (urine sample positive for β-HCG > 10 U/l)
• Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 2 years after end of antileukemic therapy
• Breast feeding
• Relapse post allogeneic stem-cell transplantation
• The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
• No consent is given for saving and propagation of pseudonymized medical data for study reasons
• Severe concomitant disease that does not allow treatment according to the protocol at the investigator’s discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
• Karnovsky / Lansky score < 50%
• Subjects unwilling or unable to comply with the study procedures
• Subjects who are legally detained in an official institute
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL4579 |
| NTR-old | NTR4720 |
| EudraCT | 2012-000793-30 |
| CCMO | NL42228.078.14 |
| OMON | NL-OMON50278 |