E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute lymphoblastic leukemia (ALL) |
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E.1.1.1 | Medical condition in easily understood language |
Acute lymphoblastic leukemia (ALL) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063626 |
E.1.2 | Term | Acute lymphocytic leukemia recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Improvement of EFS with arm B (ALLR3) compared to arm A (ALL-REZ BFM 2002) in SR patients
• Improvement of EFS after consolidation with versus without epratuzumab in SR patients |
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E.2.2 | Secondary objectives of the trial |
• Improvement of OS with arm B (ALLR3) compared to arm A (ALL-REZ BFM 2002)
• Improvement of OS after consolidation with versus without epratuzumab in SR patients
• Rate of CR2 of arm B (ALLR3) compared to arm A (ALL-REZ BFM 2002)
• Rate of SCT performed in Arm A versus Arm B
• Toxicity of Arm B (ALLR3) versus Arm A (ALL-REZ BFM 2002) in SR patients
• Toxicity of consolidation with versus without epratuzumab in SR patients
• Improvement of MRD reduction during consolidation with versus without epratuzumab in SR patients
• Rate of MRD negativity prior to SCT with Arm B (ALLR3) versus Arm A (ALL-REZ BFM 2002) in SR patients
• Rate of MRD negativity prior to SCT after consolidation with versus without epratuzumab in SR patients
• Pharmacokinetic of epratuzumab in context with Arm A and B in SR patients
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- at 4 years of arm A
- at 4 years of standard arm |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 29 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Ireland |
Israel |
Italy |
Japan |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Sweden |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |