Acute lymphoblastic leukemia (ALL) MedDRA version: 21.1 Level: LLT Classification code 10063626 Term: Acute lymphocytic leukemia recurrent System Organ Class: 100000004864
Conditions
Sponsors
Charité - University Hospital of Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
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 (stopped 01.02.2019) • Precursor B-cell immunophenotype. A specific CD22 expression level is not required • M1 or M2 status of the bone marrow after induction Are the trial subjects under 18? yes Number of subjects for this age range: 640 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: • BCR-ABL / t(9;22) positive ALL • Pregnancy or positive pregnancy test (urine sample positive for ß-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) • Subjects unwilling or unable to comply with the study procedures • Subjects who are legally detained in an official institute
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main 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 Objective: - 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 ;Primary end point(s): - SR induction/consolidation ALL-REZ BFM 2002 versus UK-ALL-R3 (randomisation 1): 10% pEFS superiority of arm B above a 65% pEFS at 4 years of arm A - SR consolidation +/- epratuzumab (randomisation 2): 10% pEFS superiority of the arm with epratuzumab above an expected 74% pEFS at 4 years of the standard arm;Timepoint(s) of evaluation of this end point: - at 4 years of arm A/B - at 4 years of standard arm +/- epratuzumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: at the end of the study;Secondary end point(s): - SR induction/consolidation: comparison of OS, toxicity, rate of CR2, and rate of MRD between treatment groups - SR consolidation +/- epratuzumab: comparison of OS, toxicity, MRD levels, rate of MRD and evaluation of pharmacokinetic parameters of Epratuzumab | — |
Countries
Australia, Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactPD Dr. Arend von Stackelberg
Charité - University Hospital of Berlin
Outcome results
None listed