E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Refractory and/or Relapsed Richters Transformation (RT) |
Síndrome de Richter recidivado o resistente al tratamiento (SR) primario |
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E.1.1.1 | Medical condition in easily understood language |
Richters Transformation (RT) |
Síndrome de Richter (SR) |
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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 | PT |
E.1.2 | Classification code | 10058728 |
E.1.2 | Term | Richter's syndrome |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the Overall Response Rate (ORR) including Partial Response (PR) and Complete Response (CR), as well as the Duration of Response (DOR). |
Determinar la tasa de respuesta global (TRG), que engloba la respuesta parcial (RP) y la respuesta completa (RC), así como la duración de la respuesta (DR) |
|
E.2.2 | Secondary objectives of the trial |
- To determine the Disease Control Rate (DCR = CR + PR + SD), as well as duration of DCR. - To determine Progression Free Survival (PFS). - To determine PFS on selinexor versus the patients PFS(s) on prior therapy(s) for RT. - To determine Overall Survival (OS). - To further evaluate toxicity of selinexor in this patient population. - To assess Quality of Life using FACT-Lym Questionnaire. |
- Determinar la tasa de control de la enfermedad (TCE = RC + RP + EE), así como la duración del control de la enfermedad. - Determinar la supervivencia sin progresión (SSP). - Determinar la SSP de selinexor frente a la SSP con los tratamientos previos recibidos por el paciente para el SR. - Determinar la supervivencia global (SG). - Evaluar exhaustivamente la toxicidad de selinexor en esta población de pacientes. - Evaluar la calidad de vida utilizando el cuestionario FACT-Lym (evaluación funcional del tratamiento oncológico, linfoma). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male and female patients older or equal to 18 years with a histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) according to the World Health Organization criteria for diagnosis of non-Hodgkins lymphoma (NHL) in the setting of RT from CLL who have had at least one, and no more than two, prior regimens including cytotoxic chemotherapy and anti-CD20 monoclonal antibodies for RT and meet criteria for refractory and/or relapsed disease. Stem cell transplantation after induction therapy is considered one therapeutic regimen. Patients who refuse or are deemed unfit by the treating physician for standard chemo-immunotherapy agents (documentation as unfit is required), but have received prior anti-CD20 monoclonal antibody therapy may be included. Patients must have disease that is objectively progressing on study entry. |
Varones y mujeres mayor de edad con diagnóstico confirmado histológicamente de linfoma difuso de linfocitos B grandes (LDCBG) de acuerdo con los criterios de la Organización Mundial de la Salud para el diagnóstico de linfoma no hodgkiniano (LNH), que presenten una transformación de LLC a SR habiendo recibido como mínimo uno y como máximo dos tratamientos previos con quimioterapia citotóxica y anticuerpos monoclonales anti-CD20 para el SR y que cumplan los criterios de enfermedad recidivada y/o resistente al tratamiento. |
|
E.4 | Principal exclusion criteria |
Patients whose Cycle 1 Day 1 is less than 1 month since completion of autologous stem cell transplantation or less than 3 months since completion of allogeneic stem cell transplantation are excluded. However, patients with radiation, chemotherapy, or immunotherapy or any other anticancer therapy less or equal to 2 weeks prior to Cycle 1 Day 1 and radio-immunotherapy 4 weeks prior to Cycle 1 Day 1 are allowed provided that patients have recovered to Grade less or equal to 1 from clinically significant effects. |
Se excluirá a los pacientes que hayan recibido un trasplante autólogo de células madre en menos de 1 mes antes del día 1 del ciclo 1 o si han transcurrido menos de 3 meses desde que el paciente recibió un trasplante alogénico de células madre. Sin embargo, se podrá incluir a los pacientes que hayan recibido radioterapia, quimioterapia, inmunoterapia o cualquier otro tratamiento antineoplásico menor o igual a 2 semanas antes del día 1 del ciclo 1 y radioinmunoterapia 4 semanas antes día 1 del ciclo 1, siempre que se hayan recuperado de los efectos adversos clínicamente significativos hasta un grado menor o igual a 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is Overall Response Rate (ORR) (as defined by the IWG Criteria) achieved by RT patients treated with single-agent selinexor. Supportive data will be provided by the duration of ORR (DOR). |
El criterio principal de valoración es la tasa de respuesta global (TRG), definida según los criterios del IWG, alcanzada por los pacientes con SR tratados con selinexor en monoterapia. Como datos complementarios se indicará la duración de la TRG (DR). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint is overall response rate (ORR) achieved on or after Day 1 of Cycle 3, or at any 2nd cycle thereafter, by RT patients who have been treated with at least one dose of single-agent selixenor. |
El criterio principal de valoración es la tasa de respuesta global (TRG) conseguida el día 1 del ciclo 3 o en cualquier momento cada 2 ciclos a partir de entonces, por los pacientes con SR tratados como mínimo con una dosis de selinexor en monoterapia. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints include the determination of the following: - DCR, including supportive data provided by duration of DCR - Progression Free Survival (PFS) - PFS on selinexor versus the patients PFS(s) on prior therapy(s) for RT - Overall Survival (OS), including OS from diagnosis and from initiation of selinexor - Further evaluation of toxicity of selinexor in this patient population - Assessment of Quality of Life using the FACT-Lym Questionnaire |
- TCE, incluida la duración del CE como dato complementario - Supervivencia sin progresión (SSP) - SSP de selinexor frente a la SSP con los tratamientos previos recibidos por el paciente para el SR - Supervivencia global (SG), incluida la SG desde el momento del diagnóstico y desde el inicio del tratamiento con selinexor - Evaluación exhaustiva de la toxicidad de selinexor en esta población de pacientes - Evaluación de la calidad de vida utilizando el cuestionario FACT-Lym |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be evaluated at end of study. |
Los criterios de valoración secundarios se evaluarán al final del estudio |
|
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 | Yes |
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) | 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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
|
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 del ultimo paciente |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |