E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated, activated B-cell (ABC) type diffuse large B-cell lymphoma (DLBCL). |
Linfoma difuso de células B grandes (LDCBG) de tipo célula B activada (CBA) no tratado con anterioridad |
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E.1.1.1 | Medical condition in easily understood language |
DLBCL is a blood cell cancer of B-lymphocytes which are part of the immune system. There are different types of DLBCL and this study is for patients with DLBCL of the ABC type who haven?t been treated |
LDCBG es un cáncer de células de sangre de linfocitos B que son parte del sistema inmune.Hay diferentes tipos de LDCBG y este estudio es para pacientes con LDCBG del tipo CBA que no han sido tratados |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012859 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) stage II |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012855 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012860 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012861 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) stage IV |
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 compare the efficacy of lenalidomide, rituximab, cyclophosphamide, doxorubicin,vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in subjects who have previously untreated ABC type DLBCL. |
Evaluar la eficacia de la quimioterapia con lenalidomida, rituximab, ciclofosfamida, doxorrubicina, vincristina y prednisona (R2-CHOP) frente a la quimioterapia con placebo, rituximab, ciclofosfamida, doxorrubicina, vincristina y prednisona (placebo-R-CHOP) en sujetos con LDCBG de tipo CBA no tratado con anterioridad. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to compare the safety of lenalidomide, rituximab, cyclophosphamide, doxorubicin,vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in subjects who have previously untreated ABC type DLBCL |
El objetivo secundario de este estudio es evaluar la seguridad de la quimioterapia con lenalidomida, rituximab, ciclofosfamida, doxorrubicina, vincristina y prednisona (R2-CHOP) frente a la quimioterapia con placebo, rituximab, ciclofosfamida, doxorrubicina, vincristina y prednisona (placebo-R-CHOP) en sujetos con LDCBG de tipo CBA no tratado con anterioridad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histologically proven Diffuse Large B-Cell Lymphoma (DLBCL) of the ABC type. -Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma (DLBCL) -Measurable Diffuse Large B-Cell Lymphoma (DLBCL) disease by Computed Tomography (CT) -Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2. Age 18 -80 years |
- LDCBG confirmado histológicamente de tipo CBA - Nuevo diagnóstico, el sujeto no ha recibido tratamiento previo para el LDCBG - Enfermedad mensurable en imágenes transversales de TC - Estado funcional <= 2 en la escala del Eastern Cooperative Oncology Group (ECOG). - Edad entre 18 y 80 años |
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E.4 | Principal exclusion criteria |
-Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma (DLBCL). -History of malignancies, other than Diffuse Large B-Cell Lymphoma (DLBCL), unless the patient has been disease free for 5 years or more. -Known seropositive for, or history of, active Human Immunodeficiency Virus (HIV) Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) -Contraindication to any drug in the chemotherapy regimen, and specifically: LVEF < 45% or peripheral neuropathy grade > =2. |
- Diagnóstico de linfoma con histología distinta del LDCBG. - Antecedentes de otras neoplasias malignas, a menos que el sujeto se haya mantenido sin enfermedad durante >= 5 años - Seropositividad o infección vírica activa conocida por el virus de a inmunodeficiencia humana (VIH), hepatitis B (VHB), hepatitis C (VHC) - Contraindicación de cualquiera de los fármacos del régimen de quimioterapia, y en concreto: FEVI < 45% o Neuropatía periférica >= grado 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Progression-free Survival (PFS) |
- Supervivencia Libre de Progresión (SLP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-This will be analyzed after a total of 192 PFS events in the ITT population have been observed. This is estimated to occur approximately 42 months after the first subject is randomized. -An interim analysis for futility is planned after a total of 96 PFS events in the ITT population have been observed. This is estimated to occur approximately 28 months after the first subject is randomized. |
- El análisis principal se realizará cuando se hayan producido los 192 acontecimientos preestablecidos de SSP (progresión/muerte) en la población por intención de tratar (IT), lo que tendrá lugar unos 42 meses después del comienzo del reclutamiento. - Está previsto un único análisis intermedio de inutilidad cuando se hayan producido 96 acontecimientos de SSP en los sujetos de la población IT de los dos grupos de tratamiento. Se calcula que se habrán producido unos 28 meses después de la aleatorización del primer sujeto. |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint -Event-free Survival (EFS) Other secondary endpoints -Overall Survival (OS) -Complete Response (CR) rate -Duration of CR -Time to next lymphoma therapy (TTNLT) -Objective response rate (ORR) -Health-related quality of life (HRQoL) as measured by the EuroQuol 5 Dimension Scale (EQ-5D) and the Functional Assessment of Cancer Therapy for Patients with Lymphoma (FACT Lym) standardized measures of health status. |
Criterio de valoración secundario fundamental - Supervivencia sin acontecimientos (SSA) Otros criterios de valoración secundarios - Supervivencia global - Tasa de respuesta completa (RC) - Duración de la RC - Tiempo hasta el siguiente tratamiento contra el linfoma (TSTL) - Tasa de respuesta objetiva (TRO) - Calidad de vida relacionada con la salud (CDVRS) determinada mediante los instrumentos normalizados de medición del estado de salud EQ-5D (Escala EuroQuol de 5 dimensiones) y FACT-Lym (Evaluación funcional del tratamiento del cáncer en pacientes con linfoma) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- At time of primary endpoint evaluation (applies for all secondary end points listed above) |
En el momento de la evaluación de la variable principal (se aplica para todos los criterios de valoración secundarios mencionados anteriormente) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
exploratory objectives ie - to compare the progression free survival 2 and genetic mutations - to explore minimal residual disease - to explore molecular markers |
Objetivos exploratorios, es decir, - Para comparar la supervivencia libre de progresión 2 y las mutaciones genéticas - Explorar la enfermedad residual mínima - Para explorar marcadores moleculares |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Belgium |
Canada |
China |
Czech Republic |
France |
Hungary |
Ireland |
Italy |
Japan |
Netherlands |
Poland |
Portugal |
Slovakia |
Spain |
Sweden |
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 date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan, whichever is the later date |
El final del ensayo se define como la fecha de la última visita del último sujeto que completó el estudio, o como la fecha de recepción de los últimos datos del último sujeto necesarios para los análisis primarios, secundarios y/o exploratorios estipulados en el protocolo y el plan de análisis estadístico, lo que ocurra después |
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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 | 8 |
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 | 8 |
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 |