E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mantle ell lymphoma |
Linfoma mantellare |
|
E.1.1.1 | Medical condition in easily understood language |
Mantle cell lymphoma |
Linfoma mantellare |
|
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 | LLT |
E.1.2 | Classification code | 10026806 |
E.1.2 | Term | Mantle zone lymphoma |
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 |
The primary objective of the phase II is to define the efficacy of ibrutinib in combination with bortezomib in patients with relapsed or refractory MCL. |
L'obiettivo primario della fase II ¿ definire l'efficacia di ibrutinib in combinazione con bortezomib in pazienti con MCL recidivo o refrattario |
|
E.2.2 | Secondary objectives of the trial |
- to determine the safety and tolerability of the RP2D of ibrutinib in combination with bortezomib - to determine the efficacy of ibrutinib in combination with bortezomib in patients with relapsed MCL followed by an ibrutinib maintenance therapy. |
- determinare la sicurezza e la tollerabilit¿ della dose di ibrutinib raccomandata per la fase II in combinazione con bortezomib - determinare l'efficacia di ibrutinib in combinazione con bortezomib in pazienti con MCL recidivo seguita da una terapia di mantenimento con ibrutinib. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Mantle cell lymphoma with either overexpression of cyclin D1 protein or evidence of t - Refractory or relapsed LCM after pretreatment with nonbortezomib-containing chemotherapy - At least one measurable lesion =11 mm (greatest transverse diameter) measured with CT scan or MRI - Adequate hematological values, hepatic and renal function - Effective method of birth control in women of childbearing potential and men who are sexually active - Negative pregnancy test in women of childbearing potential; breastfeeding women are ineligible for this trial |
• Linfoma mantellare (LCM) con sovra-espressione della ciclina D1 o con documentazione di t(11;14) • LCM refrattario o recidivante dopo precedente trattamento con chemioterapia non comprendente il bortezomib • Almeno una lesione misurabile =11 mm (diametro trasversale maggiore) con TAC o RMN • Valori ematici, funzione epatica e renale adeguati • Efficace contraccezione nelle donne in età fertile e negli uomini sessualmente attivi. • Test di gravidanza negativo nelle donne in età fertile; le donne in allattamento non possono partecipare |
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E.4 | Principal exclusion criteria |
- Prior therapy with ibrutinib or bortezomib - Actual or prior presence of the disease in the CNS - Exclusion of the following prior treatments prior to trial registration o major surgery within 4 weeks o concurrent treatment with other experimental drugs or treatment in a clinical trial within 30 days. o treatment with chemotherapy and radiotherapy within 3 weeks o vaccinated with live, attenuated vaccines within 4 weeks - History of stroke or intracranial hemorrhage within 6 months prior to trial registration - Requires anticoagulation with warfarin or equivalent vitamin K antagonists - Requires treatment with strong or moderate CYP3A inhibitors - Prior allogeneic bone marrow or solid organ transplantation |
• Precedente terapia con ibrutinib e bortezomib • Attuale o pregresso focolaio della malattia nel sistema nervoso centrale • Esclusione dei seguenti trattamenti prima della registrazione ¿ Interventi di chirurgia maggiore nelle 4 settimane precedenti ¿ Concomitante trattamento con medicamenti sperimentali o in uno studio clinico nelle 4 settimane precedenti ¿ Chemioterapie o irradiazioni nelle 3 settimane precedenti ¿ Vaccinazioni con vaccini vivi attenuati, nelle 4 settimane precedenti • Storia di ictus o sanguinamento intracranico nei 6 mesi precedenti l'inizio dello studio • Assunzione di anticoagulanti (warfarin o simili antagonisti della vitamina K) • Necessità di trattamento con inibitori forti o moderati del CYP3A • Pregresso trapianto allogenico di midollo osseo o di organo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response (OR) (combination therapy) |
Tasso di risposta alla terapia in terapia combinata |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Adverse Events; Overall response (OR) during trial treatment; Progression-free survival (PFS); Time to treatment failure; Duration of objective response |
Eventi avversi; Tasso di risposta alla terapia durante il trattamento in studio; Sopravvivenza senza progressione ; Tempo al fallimento della terapia; Durata della risposta oggettiva alla terapia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During Trial treatment; During Trial treatment; Time from registration until progression of disease or death; From registration until treatment failure; Time from first observation of CR, CRu or PR until documentation of progression, or relapse thereafter |
In corso di trattamento in studio; In corso di trattamento in studio; Dalla registrazione fino a progressione della malattia o decesso; Dalla registrazione fino al fallimento del trattamento; Tempo dalla prima osservazione di CR, CRu o PR fino alla documentazione di progressione o recidiva |
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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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
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 | 1 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Germany |
Italy |
Switzerland |
|
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 | 3 |
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 | 5 |
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 |