E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-risk and very high-risk chronic lymphocytic leukemia (CLL) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008962 |
E.1.2 | Term | Chronic lymphocytic leukaemia refractory |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study if allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) can increase event-free survival (EFS) 2 years after randomization from 40% to 70% (high-risk CLL) and from 10% to 40% (very high-risk CLL), respectively, in comparison with conventional treatment. |
|
E.2.2 | Secondary objectives of the trial |
Key secondary efficacy endpoints; 5-year overall survival (OS) from randomization; 5-year OS from registration (Stratum 2 only). Additional secondary efficacy endpoints; Clinical response (measured by iwCLL/NCI criteria); time from randomization to retreatment; minimal residual disease levels at 12 and 24 months (MRD; measured by 4-colour flow cytometry); safety (death within 3 months after randomization from any cause; non-relapse mortality; morbidity (measured by CTC criteria), chronic graft-versus-host-disease (GVHD; measured by NIH consensus project forms), quality of life (QOL; measured by EORTC QLQ C30 and HDC29), all within 2 years from randomization, impact of 7/8 vs 8/8 donor; impact of remission status at SCT; impact of the MRD status at 12 and 24 months after randomization on EFS after 12 and 24 months landmarks; FISH karyotype subset analyses. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion: Patients (age 18-65 years; PS WHO 0-1), who have active and measurable high-risk CLL (Stratum 1) or very-high-risk CLL (Stratum 2). High-risk CLL is defined as CLL without p53 lesions, relapsed between 6 and 24 months after intensive therapy (i.e. purine analogue combination therapy, autologous stem cell transplantation, or treatment of similar efficacy). Very high-risk CLL is defined as CLL, refractory or relapsed within 6 months after at least one prior chemotherapy regimen which must have included two or more cycles containing purine analogues; or refractory or relapsed within 6 months after treatment with a salvage regimen of comparable intensity given for relapse after a purine analogue-containing combination regimen; or with progressive disease with p53 lesions. |
|
E.4 | Principal exclusion criteria |
Exclusion: Patients unable to withstand RIC allo-SCT |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: EFS 2 years after randomization, in comparison with conventional treatment. EFS is defined as clinical relapse, progression, CLL-specific retreatment, or death. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | 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 | Yes |
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.8.3 |
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 | 23 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
|
2 years after randomization of the last patient enrolled |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |