E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL) |
Linfoma de Hodgkin clásico (LHc) recidivante o resistente al tratamiento (R/R) |
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E.1.1.1 | Medical condition in easily understood language |
Hodgkin Lymphoma |
Linfoma de Hodgkin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 determine the safety, tolerability and Overall Response Rate (ORR) of pembrolizumab in each of the three cohorts listed below. Cohort 1: Subjects with relapsed/refractory classical Hodgkin Lymphoma that have failed to achieve a response, or progressed after auto stem cell transplant (auto-SCT) and have relapsed after treatment with or failed to respond to brentuximab vedotin. Cohort 2: Subjects with relapsed/refractory classical Hodgkin Lymphoma that are ineligible for an auto-SCT (unable to achieve a complete or partial response to salvage therapy) and have relapsed after treatment with or failed to respond to brentuximab vedotin. Cohort 3: Subjects with relapsed/refractory classical Hodgkin Lymphoma that have failed to achieve a response, progressed after stem cell transplant and have not received treatment with brentuximab vedotin. These subjects could have received brentuximab vedotin as part of primary treatment or salvage therapy. |
Dentro de cada una de las 3 cohortes especificadas que se definen en la sección 5.1.2., y en todas ellas agrupadas, en los sujetos con linfoma de Hodgkin clásico (LHc) recidivante o resistente (R/R): (1)Objetivo: Determinar la seguridad y la tolerabilidad del pembrolizumab. Dentro de cada una de las 3 cohortes de sujetos con LHc R/R: (2)Objetivo: Evaluar la tasa de respuesta global (TRG) del pembrolizumab mediante una revisión central independiente, según los criterios de respuesta del Grupo de Trabajo Internacional (IWG) (Cheson, 2007). Hipótesis: La administración intravenosa de pembrolizumab en monoterapia deparará una TRG superior al 15% en las cohortes 1 y 3 (5% en la cohorte 2) utilizando los criterios de respuesta del IWG (Cheson, 2007), mediante una revisión centra independiente |
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E.2.2 | Secondary objectives of the trial |
(1)Objective: To evaluate ORR of pembrolizumab by investigator assessment according to the IWG response criteria (Cheson, 2007) in subjects with relapsed/refractory classical Hodgkin lymphoma and additionally by independent central review using the 5-point scale according to the Lugano Classification. (2)Objective: To evaluate Complete Remission Rate (CRR) of pembrolizumab in subjects with relapsed/refractory classical Hodgkin lymphoma. (3)Objective: To evaluate Progression Free Survival (PFS) and Duration of Response (DOR) in subjects with relapsed/refractory classical Hodgkin lymphoma. (4)Objective: To evaluate the Overall Survival (OS) in subjects with relapsed/refractory classical Hodgkin lymphoma. |
(1)Objetivo: Evaluar la TRG del pembrolizumab mediante la evaluación del investigador, conforme a los criterios de respuesta del IWG, y también mediante una revisión central independiente utilizando la escala de 5 puntos según la clasificación de Lugano. (2)Objetivo: Evaluar la tasa de remisión completa (TRC) del pembrolizumab en sujetos con linfoma de Hodgkin clásico recidivante o resistente al tratamiento (3)Objetivo: Evaluar la supervivencia sin progresión (SSP) y la duración de la respuesta (DR) del pembrolizumab en sujetos con linfoma de Hodgkin clásico recidivante o resistente al tratamiento (4)Objetivo: Evaluar la supervivencia global (SG) del pembrolizumab en sujetos con linfoma de Hodgkin clásico recidivante o resistente al tratamiento |
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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 |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal inclusion criteria |
-Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. -Be 18 years of age on day of signing informed consent. -Must have a performance status of 0 or 1 on the ECOG Performance Scale. -Must demonstrate adequate organ function as defined in the protocol, all screening labs should be performed within 28 days of treatment initiation. -Have relapsed or refractory de novo classical Hodgkin lymphoma and meet the requirements specified for one of the three cohorts in the protocol. -Have measurable disease by CT scan, as described in the protocol. -Be able to provide a core or excisional lymph node biopsy from an archival or newly obtained biopsy. -Female subjects of childbearing potential must test negative for pregnancy within 72 hours of the first dose. -Female subjects of childbearing potential and male subjects must use appropriate contraception as specified in the protocol through 120 days after the last dose of study medication. |
-Estar dispuesto a otorgar su consentimiento/asentimiento informado por escrito para el ensayo y ser capaz de hacerlo. El sujeto también podrá otorgar su consentimiento o asentimiento para las investigaciones biomédicas futuras. No obstante, podrá participar en el ensayo principal sin necesidad de participar en las investigaciones biomédicas futuras. -Tener una edad mínima de 18 años el día de la firma del consentimiento informado. -Tener un estado funcional de 0 o 1 en la escala del ECOG. -Demostrar una función orgánica adecuada según se define en el protocolo; todos los análisis de selección deben practicarse en los 28 días anteriores al inicio del tratamiento. -Presentar un linfoma de Hodgkin clásico de novo recidivante* o resistente*y cumplir uno de los criterios de inclusión indicado en las 3cohortes -Presentar enfermedad mensurable TC helicoidal como se describe en el protocolo. -Ser capaz de proporcionar una muestra de biopsia de ganglios linfáticos evaluable bien desde el archivo, o recién obtenida la biopsia en la visita de selección -Las mujeres con capacidad de procrear deberán tener una prueba de embarazo en orina o suero negativa en las 72 horas anteriores a la administración de la primera dosis de la medicación del estudio. -Las mujeres con capacidad de procrear deberán estar dispuestas a utilizar dos métodos anticonceptivos especificados en el protocolo durante 120 días después de recibir la última dosis de medicación del estudio |
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E.4 | Principal exclusion criteria |
-Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. -Has a diagnosis of immunosuppression or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. -Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. < o = a Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. -Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD.) -Additional exclusion criteria specified in the protocol. |
-Está participando o ha participado en un estudio de un fármaco o dispositivo en investigación y está recibiendo o ha recibido el tratamiento o dispositivo en investigación en las 4 semanas anteriores a la administración de la primera dosis del tratamiento. -Tiene un diagnóstico de inmunodepresión o ha recibido esteroides sistémicos o algún otro tipo de tratamiento inmunodepresor en los 7 días anteriores a la administración de la primera dosis del tratamiento del ensayo. Ha recibido un anticuerpo monoclonal previo en las 4 semanas anteriores al día 1 del estudio o no se ha recuperado (es decir, a un grado < o = a 1 o al valor basal) de los acontecimientos adversos provocados por los fármacos administrados más de 4 semanas antes. -Ha recibido un alotrasplante de células madre hematopoyéticas en los 5 años precedentes. (Si el trasplante se realizó más de 5 años antes, el sujeto podrá participar siempre que no presente síntomas de EICH.) -El resto de criterios de inclusión se reflejan en el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received MK-3475, including serious adverse events (SAEs) and events of clinical interest (ECIs). The primary efficacy endpoint is the Overall Response Rate (ORR), defined as the proportion of subjects in the analysis population who have complete remission (CR) or partial remission (PR) using IWG criteria, Cheson 2007 at any time during the study. Response for the primary analysis will be determined by central review. |
La seguridad será evaluada mediante la cuantificación de las toxicidades en los sujetos que han recibido MK-3474, incluidos los acontecimientos adversos graves (SAEs) y los eventos de interés clínico (ECIs). El criterio de valoración principal de la eficacia es la tasa de respuesta global (TRG), que se define como la proporción de sujetos de la población de análisis que presentan una remisión completa (RC) o una remisión parcial (RP) según los criterios del IWG (Cheson 2007) en cualquier momento durante el estudio. A efectos del análisis principal, la respuesta se determinará mediante una revisión centralizada. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At each cycle and as clinically deemed |
En cada ciclo que se considere clínicamente |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are duration of response, progression-free survival and overall survival. |
Las variables secundarias son la duración de la respuesta, Supervivencia sin progresión y Supervivencia global |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At each cycle and as clinically deemed |
En cada ciclo que se considere clínicamente |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Brazil |
Canada |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Netherlands |
Norway |
Russian Federation |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 overall trial ends when the last subject completes the last trial visit, discontinues from the trial or is lost to follow-up (i.e. the subject is unable to be contacted by the investigator). |
El ensayo en su conjunto finalizará cuando el último sujeto complete la última visita del ensayo, se retire del ensayo o se pierda para el seguimiento (es decir, cuando el investigador no pueda ponerse en contacto con el sujeto). |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |