E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
INDOLENT NON-HODGKIN'S LYMPHOMA |
Linfoma no-Hodgkin indolente |
|
E.1.1.1 | Medical condition in easily understood language |
INDOLENT NON-HODGKIN'S LYMPHOMA |
Linfoma no-Hodgkin indolente |
|
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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
Progression-free survival in patients with follicular lymphoma, investigator-assessed according to the Revised Response Criteria for Malignant Lymphoma up to 7.5 years |
Supervivencia libre de progresión (SLP) evaluada por el investigador según los criterios de respuesta Revised Response Criteria for Malignant Lymphoma hasta 7.5 años |
|
E.2.2 | Secondary objectives of the trial |
PFS in the overall study population, investigator-assessed up to approximately 7.5 years PFS in the overall study population, Independent Review Committee assessed up to approximately 7.5 years Response (OR and CR) assessed by the investigator up to 168 days Response (OR and CR) assessed by Independent Review Committee 168 days OS up to approximately 10.7 years Event-free survival up to approximately 7.5 years Disease-free survival up to approximately 7.5 years Duration of response up to approximately 7.5 years Time to next anti-lymphoma treatment up to approximately 10.7 years Incidence of adverse events up to approximately 10.7 years Patient-reported outcomes (Functional Assessment of Cancer Therapy for Lymphoma scale, EuroQol EQ-5D questionnaire) up to approximately 7.5 years Medical resource utilization (hospitalizations, subsequent drug Identificador del archivo XML: therapies, medical and surgical procedures) up to approximately 7.5 years |
SLP evaluada por el investigador hasta aproximadamente 7,5 años SLP evaluada por el comité de revisión independiente (CRI) , hasta aproximadamente 7,5 años Tasas de respuesta global y de respuestas completas (RC) tras el final del tratamiento de inducción, según lo evaluado por el investigador Tasas de respuesta global y RC tras el final del tratamiento de inducción, según lo evaluado por el CRI Supervivencia global, la supervivencia libre de episodios (SLEp), la supervivencia libre de enfermedad (SLE), la duración de la respuesta hasta aproximadamente 7,5 años y el tiempo hasta el siguiente tratamiento contra el linfoma entre los dos grupos, hasta aproximadamente 10.7 años Incidencia de eventos adversos hasta aproximadamente 10.7 años Evaluar resultados comunicados por los pacientes (RCP), hasta aproximadamente 7,5 años Evaluar la utilización de recursos médicos, hasta aproximadamente 7,5 años |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Biomarker Samples (Stored in the Roche Clinical Repository) |
Recogida de muestras para el Banco de Muestras Clínicas de Roche (RCR), INCLUIDO EN EL PROTOCOLO INICIAL, versión 14 de enero de 2011 |
|
E.3 | Principal inclusion criteria |
Adult patients, >/= 18 years of age CD20-positive indolent B-cell non-Hodgkin's lymphoma (follicular lymphoma or splenic, nodal or extranodal marginal zone lymphoma) Stage II or IV disease, or Stage II bulky disease At least one bi-dimensionally measurable lesion (>2 cm in its largest dimension by CT scan or MRI) Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 Adequate hematologic function" |
Edad mayor igual 18 años. LNH de células B, indolente y CD20 positivo (linfoma folicular, LZM esplénico, LZM ganglionar o LZM extraganglionar.) Enfermedad en estadio III o IV o enfermedad de bulky en estadio II. Al menos una lesión medible en dos dimensiones (> 2 cm en su dimensión mayor mediante TAC o RM). Estado funcional ECOG de 0, 1 o 2 Función hematológica adecuada |
|
E.4 | Principal exclusion criteria |
Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma - Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's macroglobulinaemia - Ann Arbor Stage I disease - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy, known hypersensitivity to any of the study drugs or sensitivity to murine products, or history of sensitivity to mannitol - For patients with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma with chemotherapy, immunotherapy, or radiotherapy - For patients with non-follicular lymphoma: prior treatment with chemotherapy or immunotherapy - History of prior malignancy with the exception of curatively treated basal or squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix - Known active infection, or major episode of infection within 4 week prior to the start of Cycle 1 - Positive for HIV, HTLV1, hepatitis C or chronic hepatitis B" |
-Linfoma del sistema nervioso central, linfoma leptomeníngeo o datos histológicos de transformación en linfoma de alto grado o linfoma difuso de linfocitos B grandes. Linfoma folicular de grado 3b, LLCP o MW. Enfermedad en estadio I de Ann Arbor Hipersensibilidad conocida a productos de origen murino, hipersensibilidad a manitol, a alguno de los fármacos del estudio. En los pacientes con linfoma folicular: tratamiento previo para el LNH con quimioterapia, inmunoterapia o radioterapia. En los pacientes con linfoma no folicular: tratamiento previo con quimioterapia o inmunoterapia Antecedentes de neoplasias malignas previas a excepción de carcinoma de piel de células basales o escamosas tratado con intención curativa y carcinoma de cuello de utero in situ de bajo grado Infección activa conocida por bacterias, virus, hongos, micobacterias, parásitos u otras infecciones (excepto micosis de las uñas) o cualquier episodio importante de infección que requiera tratamiento con antibióticos IV u hospitalización (en relación con la finalización del ciclo de antibióticos) en las 4 semanas previas al comienzo del ciclo 1. Resultados positivos de las pruebas de hepatitis B crónica, C VIH, HTLV1. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint, PFS in patients with follicular lymphoma, is defined as the time from randomization to the first occurrence of progression or relapse as assessed by the investigator according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007; see Appendix C), or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment, or if no tumor assessments were performed after the baseline visit, at the time of randomization. |
El criterio de valoración principal de la eficacia, la SLP en los pacientes con linfoma folicular, se define como el tiempo transcurrido entre la aleatorización y el primer episodio de progresión o recidiva, según lo evaluado por el investigador con arreglo a los Criterios de respuesta revisados para el linfoma maligno, o la muerte por cualquier causa |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 7.5 years |
Hasta aproximadamente 7.5 años |
|
E.5.2 | Secondary end point(s) |
Progression-free survival in the overall study population, investigatorassessed Progression-free survival, Independent Review Committee - assessed Response (overall response and complete response), investigatorassessed Response (overall response and complete response), Independent Review Committee - assessed Overall survival Event-free survival Disease-free survival Duration of response Time to next anti-lymphoma treatment Safety: Incidence of adverse events Patient-reported outcomes (Functional Assessment of Cancer Therapy for Lymphoma scale, EuroQol EQ-5D questionnaire) Medical resource utilization (hospitalizations, subsequent drug therapies, medical and surgical procedures) |
Supervivencia libre de progresión en la población total del estudio, evaluados por el investigador Supervivencia libre de progresión, evaluado por un Comité de Revisión Independiente - Respuesta (respuesta global y respuesta completa), evaluados por el investigador Respuesta (respuesta global y respuesta completa), evaluado por Comité de Revisión Independiente - La supervivencia global Supervivencia libre de eventos Supervivencia libre de enfermedad Duración de la respuesta Tiempo al siguiente tratamiento contra el linfoma Seguridad: La incidencia de eventos adversos Paciente informó de los resultados (evaluación funcional de la terapia contra el cáncer de linfoma escala, EuroQol EQ-5D cuestionario) La utilización de recursos médicos (hospitalizaciones, tratamientos posteriores de medicamentos, procedimientos médicos y quirúrgicos) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
84 days for induction 168 day for Response 7.5 to 10.7 years for all other end points |
84 dias para inducción 168 dias para respuesta 7.5 to 10.7 años para otros criterios de evaluación |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
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 |
Argentina |
Australia |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
China |
Colombia |
El Salvador |
Guatemala |
Ireland |
Japan |
Macedonia, the former Yugoslav Republic of |
Mexico |
Panama |
Peru |
Russian Federation |
South Africa |
Taiwan |
Ukraine |
United States |
|
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
|
Last Patient Last Visit |
ultima visita ultimo paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |