E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mantle Cell Lymphoma |
Linfoma de células del manto |
|
E.1.1.1 | Medical condition in easily understood language |
Mantle Cell Lymphoma |
Linfoma de células del manto |
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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 |
Comparar la eficacia, medida por la supervivencia sin progresión (SSP) determinada mediante una revisión central independiente. |
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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 |
Secundarios: • Evaluar la eficacia, medida mediante los parámetros siguientes: − Supervivencia sin progresión determinada por la evaluación del investigador. − Tasa de respuesta global (TRG), determinada mediante la revisión central independiente y por la evaluación del investigador. − Duración de la respuesta (DR), determinada mediante revisión central independiente y por la evaluación del investigador. − Supervivencia global (SG) − Tasa de respuesta completa (RC) o respuesta metabólica completa determinada mediante revisión central independiente y por la evaluación del investigador. − Tiempo que tarda en alcanzarse la respuesta terapéutica, determinado mediante revisión central independiente y por la evaluación del investigador. − Resultados comunicados por el paciente. − Evaluar la seguridad y la tolerabilidad. |
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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 |
- Adultos ≥ 70 años en el momento de la firma del consentimiento informado o - 65-69 años con que impidan un trasplante autólogo de células madre - Dagnóstico confirmado histológicamente de LCM - No haber recibido tratamiento sistémico previo para LCM - Enfermedad cuantificable mediante TAC/ RM - Estado Funcional 0-2 conforme a The Eastern Cooperative Oncology Group (ECOG). - Funciones medulares y orgánicas adecuadas |
|
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 |
• Afección conocida del sistema nervioso central por linfoma • Pacientes para los que el objetivo del tratamiento es la desbulking tumoral antes del trasplante de células madre • Enfermedad cardiovascular clínicamente significativa • Antecedentes de trastorno hemorrágico grave • Incapacidad de tragar cápsulas o enfermedadquen significativamente afectando la función gastrointestinal • Infección activa de hongos, bacterias y/o virales que requiera terapia sistémica • Necesidad de tratamiento continuo con un inhibidor o inductor potente del CYP3A |
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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. |
El análisis principal de la eficacia de la SSP se realizará según la evaluación mediante revisión central independiente, siguiendo la clasificación de Lugano para el LAH y definido como el tiempo desde la randomización hasta la fecha de la primera documentación de progresión de la enfermedad o muerte, lo que ocurra primero. |
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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 |
Fecha de la primera documentación de progresión de la enfermedad o muerte, lo que ocurra primero. |
|
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 |
• Supervivencia sin progresión según lo determinado por la evaluación del investigador utilizando la Clasificación de Lugano para el NHL, y definida como el tiempo desde la aleatorización hasta la fecha de la primera documentación de progresión o fallecimiento, lo que ocurra primero • Tasa de respuesta global, definida como la proporción de pacientes que logran una CR o respuesta parcial (PR), determinada por la revisión central independiente y por la evaluación del investigador • Duración de la respuesta, determinada por la revisión central independiente y por la evaluación del investigador, y definida como el tiempo a partir de la fecha en que se cumplen por primera vez los criterios de respuesta hasta la fecha en que la progresión de la enfermedad esté objetivamente documentada o la muerte, lo que ocurra primero • Supervivencia global, definida como el tiempo desde la aleatorización hasta la fecha de la muerte por cualquier motivo • Tasa de CR o respuesta metabólica completa, definida como la proporción de pacientes que logran una respuesta metabólica completa o CR, determinada por la revisión central independiente y por la evaluación del investigador • Tiempo de respuesta, según lo determinado por la revisión central independiente y por la evaluación del investigador, y definido como el tiempo de la aleatorización a la primera documentación de la respuesta • Resultados reportados por el paciente medidos por los cuestionarios EQ-5D-5L y EORTC QLQ-C30 • Parámetros de seguridad, incluidos AE, EAS, pruebas clínicas de laboratorio, exámenes físicos y signos vitales |
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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. |
Todos los criterios de evaluación excepto los dos útlimos han definido los criterios incluidos. Además, los PRO se miden en cada visita durante el tratamiento. Los parámetros de seguridad se miden en cada visita. Los acontecimientos adversos se notificarán hasta 30 días después de la última dosis de zanubrutinib o bendamustina, o hasta 90 días después de la última dosis de rituximab, lo que ocurra más tarde. |
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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 | 11 |
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 | 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 |
Australia |
Austria |
Belgium |
Canada |
China |
Denmark |
France |
Germany |
Ireland |
Italy |
Japan |
Netherlands |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Taiwan |
Turkey |
Ukraine |
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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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 |