E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mantle Cell Lymphoma |
Linfoma a cellule mantellari |
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E.1.1.1 | Medical condition in easily understood language |
Mantle Cell Lymphoma |
Linfoma a cellule mantellari |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061275 |
E.1.2 | Term | Mantle cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To assess the efficacy of INCB050465 in terms of objective response rate (ORR) in subjects with mantle cell lymphoma (MCL) that is relapsed or refractory after at least 1 but no more than 3 prior systemic treatment regimens. |
Valutare l¿efficacia di INCB050465 in termini di tasso di risposta obiettiva (ORR) in soggetti con linfoma a cellule mantellari (MCL) recidivante o refrattario dopo almeno 1 ma non pi¿ di 3 regimi precedenti di trattamento sistemico. |
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E.2.2 | Secondary objectives of the trial |
¿ To assess duration of response (DOR). ¿ To assess complete response rate (CRR). ¿ To assess progression-free survival (PFS). ¿ To assess overall survival (OS). ¿ To assess the best percentage change in target lesion size. ¿ To characterize the safety and tolerability of INCB050465. |
- Valutare la durata della risposta (DOR) - Valutare il tasso di risposta completa (CRR) -Valutare la sopravvivenza libera da progressione (PFS) - Valutare la sopravvivenza complessiva (OS) -Valutare la migliore variazione percentuale nelle dimensioni delle lesioni target - Caratterizzare la sicurezza e la tollerabilit¿ di INCB050465. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11;14), who have had at least 1 but no more than 3 prior systemic treatment regimens. • Men and women, aged 18 or older • Documented failure to achieve at least PR with or documented disease progression after the most recent treatment regimen. • Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of = 1 lesion that measures > 1.5 cm in the longest dimension and = 1.0 cm in the longest perpendicular dimension as assessed by CT or magnetic resonance imaging (MRI). • Eastern Cooperative Oncology Group (ECOG) performance status of = 2. |
Soggetti affetti da MCL patologicamente confermato, con documentata sovraespressione della ciclina D1 o traslocazione t (11;14), che abbiano ricevuto almeno 1 ma non più di 3 regimi precedenti di trattamento sistemico. • Uomini e donne di età pari o superiore a 18 anni (pari o superiore a 19 anni nella Corea del Sud). • Documentazione di mancato raggiungimento di almeno una PR, con o senza progressione di malattia documentata, dopo il regime di trattamento più recente. • Linfoadenopatia o neoplasia linfoide extranodale radiologicamente misurabile (definita come presenza di =1 lesione che misuri >1,5 cm nella dimensione maggiore e =1,0 cm nella dimensione perpendicolare maggiore, come valutato mediante TAC o risonanza magnetica [RMN]). • Stato di validità secondo l’Eastern Cooperative Oncology Group (ECOG) (Gruppo cooperativo orientale di oncologia) =2.
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E.4 | Principal exclusion criteria |
• History of central nervous system lymphoma (either primary or metastatic). • Prior treatment with idelalisib, other selective phosphoinositide 3-kinase (PI3K) d inhibitors, or a pan-PI3K inhibitor. • Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of first dose of study treatment. • Active graft-versus-host disease. • Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for HBV-DNA; these subjects should be considered for prophylactic antiviral therapy. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA. . |
• Anamnesi di linfoma del sistema nervoso centrale (primario o metastatico). • Precedente trattamento con idelalisib, o con altri inibitori selettivi della fosfoinositide 3-chinasi (PI3K) d o con un pan-inibitore di PI3K. • Trapianto allogenico di cellule staminali entro gli ultimi 6 mesi o trapianto autologo di cellule staminali entro gli ultimi 3 mesi precedenti la data della prima dose di trattamento dello studio. • Malattia attiva da rigetto del trapianto. • Epatite B (HBV) o infezione da epatite C (HCV). I soggetti positivi per l’antigene di superficie dell’epatite B o per l’anticorpo anti-core dell’epatite B saranno eleggibili se risulteranno negativi per HBV-DNA: questi soggetti dovranno essere considerati per la terapia profilattica antivirale. I soggeti positivi per l’anticorpo anti HCV saranno eleggibili se saranno negativi per HCV-RNA.
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR defined as the percentage of subjects with a complete response (CR) or partial response (PR) as determined by independent review committee (IRC) assessment of response according to computed tomography (CT)-based response criteria for lymphomas.
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ORR definito come percentuale di soggetti che ottengono una risposta completa (CR) o una risposta parziale (PR), determinata in base alla valutazione della risposta da parte di un comitato di revisione indipendente (IRC) secondo i criteri di risposta per i linfomi basati sulla tomografia computerizzata (TC).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Response data will be analyzed when all subjects in the respective cohort have received at least 1 postbaseline disease assessment or have progressed, withdrawn from the study, or died |
I dati relativi alla risposta saranno analizzati quando tutti i soggetti nella rispettiva coorte avranno ricevuto almeno1 valutazione postbasale della malattia, o avranno progredito o si saranno ritirati dallo studio o saranno morti
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E.5.2 | Secondary end point(s) |
¿ DOR defined as the time from first documented evidence of CR or PR until disease progression or death from any cause among subjects who achieve an objective response, as determined by radiographic disease assessment provided by an IRC. ¿ CRR defined as the percentage of subjects with a CR as defined by response criteria for lymphomas as determined by an IRC. ¿ PFS defined as the time from the date of the first dose of study treatment until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause. ¿ Overall survival defined as the time from the date of the first dose of study treatment until death from any cause. ¿ Best percentage change in target lesion size from baseline, where target lesion size is measured by the sum of the product of diameters of all target lesion sizes. ¿ Safety measured by adverse events (AEs), 12-lead electrocardiograms (ECGs), chemistry and hematology laboratory values, vital signs, and physical examinations. |
- DOR definita come l¿intervallo di tempo dalla prima evidenza documentata di CR o PR fino alla progressione di malattia o al decesso dovuto a qualsiasi causa nei soggetti che ottengono una risposta obiettiva, determinata in base alla valutazione radiologica della malattia fornita da un IRC. - CRR definita come percentuale di soggetti che ottengono una CR, come determinata da un IRC secondo i criteri di risposta per i linfomi. - PFS definita come l¿intervallo di tempo dalla data della prima dose di trattamento dello studio fino alla prima data di progressione di malattia, determinata in base alla valutazione radiologica della malattia fornita da un IRC, o al decesso per qualsiasi causa. - Sopravvivenza complessiva definita come l¿intervallo di tempo dalla data della prima dose di trattamento dello studio fino al decesso per qualsiasi causa. - Migliore variazione percentuale nelle dimensioni delle lesioni target rispetto al basale, ove le dimensioni delle lesioni target sono ottenute dalla somma del prodotto dei diametri di tutte le lesioni target. - Sicurezza misurata in base agli eventi avversi (EA), elettrocardiogrammi (ECG) a 12 derivazioni, valori degli esami di laboratorio chimici ed ematologici, segni vitali ed esami obiettivi. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
Durante lo studio |
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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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | Information not present in EudraCT |
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 |
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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 the study will be when all subjects have met any of the study discontinuation criteria or have completed at least 24 months of study participation (starting from first dose of INCB50465). |
La fine dello studio sarà quando tutte le persone avranno soddisfatto uno dei criteri di sospensione dello studio o avranno partecipato allo studio per almeno 24 mesi (a partire dalla prima dose di INCB50465). |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |