E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mantle Cell Lymphoma |
linfoma mantellare |
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E.1.1.1 | Medical condition in easily understood language |
Mantle Cell Lymphoma |
linfoma mantellare |
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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 compare efficacy, as measured by progression-free survival (PFS) determined by independent central review |
Confrontare l’efficacia, misurata mediante la sopravvivenza libera da progressione (Progression-Free Survival, PFS) determinata tramite revisione centrale indipendente |
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E.2.2 | Secondary objectives of the trial |
Secondary: • To evaluate efficacy, as measured by the following: - Progression-free survival determined by investigator assessment - Overall response rate (ORR), as determined by independent central review and by investigator assessment - Duration of response (DOR), as determined by independent central review and by investigator assessment - Overall survival (OS) - Rate of complete response (CR) or complete metabolic response determined by independent central review and by investigator assessment - Time to response, as determined by independent central review and by investigator assessment - Patient reported outcomes - To evaluate safety and tolerability |
Secondari: • Valutare l’efficacia, misurata mediante quanto indicato di seguito: - Sopravvivenza libera da progressione, determinata mediante valutazione dello sperimentatore; - Tasso di risposta complessiva (Overall Response Rate, ORR), determinato mediante revisione centrale indipendente e valutazione dello sperimentatore; - Durata della risposta (Duration of Response, DOR), determinata mediante revisione centrale indipendente e valutazione dello sperimentatore; - Sopravvivenza complessiva (Overall Survival, OS); - Tasso di risposta completa (Complete Response, CR) o di risposta metabolica completa, determinato mediante revisione centrale indipendente e valutazione dello sperimentatore; - Tempo alla risposta, determinato mediante revisione centrale indipendente e valutazione dello sperimentatore; - Esiti riferiti dai pazienti. - Valutare la sicurezza e la tollerabilità. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• = 70 years of age at the time of informed consent, OR • 65-69 years of age with comorbidities precluding autologous stem cell transplantation • Histologically confirmed diagnosis of MCL • No prior systemic treatments for MCL • Measurable disease by CT/MRI • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 • Adequate marrow and organ function |
• = 70 years of age at the time of informed consent, OR • 65-69 years of age with comorbidities precluding autologous stem cell transplantation • Histologically confirmed diagnosis of MCL • No prior systemic treatments for MCL • Measurable disease by CT/MRI • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 • Adequate marrow and organ function |
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E.4 | Principal exclusion criteria |
• Known central nervous system involvement by lymphoma • Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant • Clinically significant cardiovascular disease • History of severe bleeding disorder • Unable to swallow capsules or disease significantly affecting gastrointestinal function • Active fungal, bacterial and/or viral infection requiring systemic therapy • Requires ongoing treatment with a strong CYP3A inhibitor or inducer |
• Known central nervous system involvement by lymphoma • Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant • Clinically significant cardiovascular disease • History of severe bleeding disorder • Unable to swallow capsules or disease significantly affecting gastrointestinal function • Active fungal, bacterial and/or viral infection requiring systemic therapy • Requires ongoing treatment with a strong CYP3A inhibitor or inducer |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PFS as determined by independent central review using the Lugano Classification for NHL and defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first. |
The primary endpoint is PFS as determined by independent central review using the Lugano Classification for NHL and defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
date of first documentation of disease progression or death, whichever occurs first |
date of first documentation of disease progression or death, whichever occurs first |
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E.5.2 | Secondary end point(s) |
• Progression-free survival as determined by investigator assessment using the Lugano Classification for NHL, and defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first • Overall response rate, defined as the proportion of patients who achieve a CR or partial response (PR), determined by independent central review and by investigator assessment • Duration of response, as determined by independent central review and by investigator assessment, and defined as the time from the date that response criteria are first met to the date that disease progression is objectively documented or death, whichever occurs first • Overall survival, defined as the time from randomization to the date of death due to any reason • Rate of CR or complete metabolic response, defined as the proportion of patients who achieve a CR or complete metabolic response, determined by independent central review and by investigator assessment • Time to response, as determined by independent central review and by investigator assessment, and defined as time from randomization to the first documentation of response • Patient-reported outcomes as measured by the EQ-5D-5L and EORTC QLQ-C30 questionnaires • Safety parameters, including AEs, SAEs, clinical laboratory tests, physical exams, and vital signs |
• Progression-free survival as determined by investigator assessment using the Lugano Classification for NHL, and defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first • Overall response rate, defined as the proportion of patients who achieve a CR or partial response (PR), determined by independent central review and by investigator assessment • Duration of response, as determined by independent central review and by investigator assessment, and defined as the time from the date that response criteria are first met to the date that disease progression is objectively documented or death, whichever occurs first • Overall survival, defined as the time from randomization to the date of death due to any reason • Rate of CR or complete metabolic response, defined as the proportion of patients who achieve a CR or complete metabolic response, determined by independent central review and by investigator assessment • Time to response, as determined by independent central review and by investigator assessment, and defined as time from randomization to the first documentation of response • Patient-reported outcomes as measured by the EQ-5D-5L and EORTC QLQ-C30 questionnaires • Safety parameters, including AEs, SAEs, clinical laboratory tests, physical exams, and vital signs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
all of the secondary endpoints except last two have defined timepoints included above. In an addition PRO's are measured at every visit during treatment. Safety parameters are measured at every visit. Adverse events will be reported until 30 days after the last dose of zanubrutinib or bendamustine, or until 90 days after the last dose of rituximab, whichever occurs later. |
all of the secondary endpoints except last two have defined timepoints included above. In an addition PRO's are measured at every visit during treatment. Safety parameters are measured at every visit. Adverse events will be reported until 30 days after the last dose of zanubrutinib or bendamustine, or until 90 days after the last dose of rituximab, whichever occurs later. |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | 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
| 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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
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 |
Australia |
Canada |
China |
Japan |
New Zealand |
Russian Federation |
Taiwan |
Turkey |
Ukraine |
United States |
Austria |
Belgium |
Denmark |
France |
Germany |
Ireland |
Italy |
Netherlands |
Poland |
Portugal |
Romania |
United Kingdom |
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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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |