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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Improvement of CR2 rates after induction with ALL R3 with bortezomib versus without bortezomib in HR relapsed ALL patients |
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E.2.2 | Secondary objectives of the trial |
Improvement of EFS and OS rates
Improvement of EFS and OS rates
Improvement of MRD reduction after induction with versus without bortezomib
Improvement of MRD load prior to SCT
Increasing the proportion of HR patients reaching SCT
Prognostic relevance of MRD pre SCT
Improvement of CR2 and/or MRD rates during consolidation
Toxicity of induction with versus without bortezomib
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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 date of inclusion into the study
• Meeting HR criteria (any T BM relapse, early/very early isolated BM relapse, very early isolated/combined 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 day prior to study enrolment that interfere with this protocol, except trials for primary ALL
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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 12 months after end of anti-leukemic therapy
• Breast feeding
• Relapse post allogeneic stem-cell transplantation
• Neuropathy > II°
• The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
• Objection to the study participation by a minor patient, able to object
• Any patient being dependent on the investigator
• 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
- 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Randomized induction trial: Improvement of CR2 rates with standard chemotherapy + Bortezomib (Arm B) quantified by cytology compared with standard chemotherapy (Arm A) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint will be evaluated at week 5 after induction. |
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E.5.2 | Secondary end point(s) |
- Improvement of three years EFS and OS, rate of patients reaching HSCT, MRD rates post induction and pre-HSCT, prognostic relevance of MRD pre HSCT, CR2 and MRD rates during consolidation, toxicity of randomized arms |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- EFS, OS: three years after recruitment is completed
- toxicity: together with the primary endpoint
- MRD rates: 9 weeks after primary endpoint |
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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 | No |
E.6.11 | Pharmacogenomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 198 |
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 |
Israel |
Japan |
New Zealand |
Belgium |
Denmark |
Finland |
France |
Germany |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Sweden |
Switzerland |
Czechia |
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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 | 6 |
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 | 6 |
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 |