E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) |
Leucemia Linfocitica Cronica recidivante/refrataria (LLC) |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the blood and bone marrow |
Tumore del sangue e del midollo osseo |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068852 |
E.1.2 | Term | B-cell chronic lymphocytic leukaemia |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate the efficacy of GDC-0199 and rituximab (GDC-0199+R) compared with bendamustine and rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) as measured by investigator-assessed progression-free survival (PFS). |
Valutare l’efficacia di GDC-0199 e rituximab (GDC-0199+R) rispetto a bendamustina e rituximab (BR) in pazienti con Leucemia Linfocitica Cronica recidivante o refrattaria misurata sulla sopravvivenza libera da progressione valutata dallo sperimentatore. |
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E.2.2 | Secondary objectives of the trial |
• To analyze Independent Review Committee (IRC) & investigator-assessed PFS in the subset of CLL patients with 17p deletion
• To evaluate PFS as assessed by an IRC.
• To evaluate rates of OR, PR, and CR and CRi at 12 weeks after Day 1 of the last cycle of multi-agent therapy.
• To evaluate OR, PR, CR, and CRi rates 12 weeks after Day 1 of the last cycle of multi-agent therapy, as determined by the IRC.
• To evaluate overall survival (OS).
• To evaluate duration of response for patients with a best overall response of CR, CRi, or PR.
• To evaluate time to next anti-CLL treatment.
• To evaluate the proportion of patients with MRD-negativity at the disease response assessment time points. |
• Analizzare la SLP valutata dal Comitato di revisione indipendente (CRI) nel sottoinsieme di pazienti LLC con delezione 17p
• Valutare la SLP come definita da un CRI.
• Valutare i tassi di OR, PR, CR e CRi 12 settimane dopo il Giorno 1 dell’ultimo ciclo della terapia multi-agente.
Valutare i tassi di OR, PR, CR e CRi 12 settimane dopo il Giorno 1 dell’ultimo ciclo della terapia multi-agente, come determinato dal CRI.
• Valutare la sopravvivenza complessiva (overall survival, OS).
• Valutare la durata della risposta (duration of response, DOR) per pazienti con una migliore risposta globale di CR, CRi o PR.
• Valutare il tempo trascorso fino al successivo trattamento anti LLC (time to next treatment, TTNT).
• Valutare la percentuale di pazienti con negatività alla malattia residua minima (minimal residual disease, MRD) nei punti temporali di valutazione della risposta della malattia.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2008).
Patients must have peripheral blood B-lymphocyte counts which clonally express CD5, CD19/20 and CD23 and are either kappa or lambda light-chain restricted.
Pro-lymphocytes may comprise no more than 55% of total circulating lymphocytes.
At initial diagnosis of CLL (ie, prior to front-line treatment), the peripheral lymphocyte count must have been >5000/mm3. Patients must meet the following criteria for relapsed or refractory CLL (per the iwCLL guidelines [Hallek et al. 2008]):
-Relapsed disease: a patient who previously achieved a CR or PR, but after a period of 6 months or more demonstrates evidence of progression;
-refractory disease: treatment failure or disease progression within 6 months of the last anti-leukemia therapy. |
Diagnosi di LLC che soddisfa i criteri diagnostici pubblicati (Hallek et al. 2008). I pazienti devono avere conte di linfociti B periferici con espressione clonale di CD5, CD19/20 e CD23 e ristretti alle catene leggere kappa o lambda. I pro-linfociti possono costituire non più del 55% dei linfociti circolanti totali. Alla diagnosi iniziale di LLC (cioè prima del trattamento di prima linea), la conta di linfociti periferici deve essere stata 5000/mm3. I pazienti devono soddisfare i criteri della LLC recidivante o refrattaria (secondo le linee guida iwCLL [Hallek et al. 2008]).
• Malattia recidivante: un paziente che precedentemente ha raggiunto una CR o una PR ma che dopo un periodo di 6 mesi o più presenta evidenza di progressione.
• Malattia refrattaria: fallimento del trattamento o progressione della malattia entro 6 mesi dall’ultima terapia antileucemica. |
|
E.4 | Principal exclusion criteria |
Transformation of CLL to aggressive NHL (eg, Richter's transformation, prolymphocytic leukemia, or DLBCL) or CNS involvement by CLL. |
• Trasformazione della LLC in LNH (linfoma non-Hodgkin) aggressivo (ad es. sindrome di Richter, leucemia prolinfocitica o LDGCB) o coinvolgimento del SNC da parte della LLC. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy of GDC-0199 and rituximab (GDC-0199+R) compared with bendamustine and rituximab (BR) in patients with relapsed or refractory CLL as measured by investigator-assessed progression-free survival (PFS). |
Valutare l’efficacia di GDC-0199 e rituximab (GDC-0199+R) rispetto a bendamustina e rituximab (BR) in pazienti con leucemia linfocitica cronica recidivante o refrattaria (LLC) misurata sulla sopravvivenza libera da progressione (SLP) valutata dallo sperimentatore. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
September 2016 & September 2017 |
Settembre 2016 e Settembre 2017 |
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E.5.2 | Secondary end point(s) |
To analyze Independent Review Committee (IRC)-assessed PFS in the subset of CLL patients with 17p deletion identified by fluorescence in situ hybridization (FISH) testing performed at a central laboratory. |
Analizzare la SLP valutata dal Comitato di revisione indipendente (CRI) nel sottoinsieme di pazienti LLC con delezione 17p identificata mediante test di ibridizzazione fluorescente in situ (fluorescence in situ hybridization, FISH) eseguito presso un laboratorio centrale. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
September 2017
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Settembre 2017 |
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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 | No |
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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient-Reported Outcome Objectives |
obiettivi di eventi riportati dal soggetto |
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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 | No |
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 | No |
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) | No |
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
| 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Belgium |
Canada |
Denmark |
France |
Italy |
Austria |
Netherlands |
Sweden |
Australia |
Czech Republic |
Finland |
Germany |
Hungary |
Korea, Republic of |
Spain |
Poland |
Taiwan |
United Kingdom |
United States |
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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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The end of study will be approximately 3 years after last patient is enrolled allowing for completion of the maximum duration of planned therapy (in the absence of disease progression) as well as at least one year of follow-up for all patients. |
La fine dello studio sarà circa 3 anni dopo l’arruolamento dell’ultimo paziente per consentire il completamento della durata massima della terapia pianificata (in assenza di progressione della malattia) ed almeno un anno di follow-up per tutti i pazienti. |
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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 | 5 |
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 | 5 |
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 |