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    The EU Clinical Trials Register currently displays   38529   clinical trials with a EudraCT protocol, of which   6333   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2014-004482-24
    Sponsor's Protocol Code Number:MK3475-087
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-05-08
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2014-004482-24
    A.3Full title of the trial
    A Phase II clinical trial of MK-3475 (pembrolizumab) in subjects with relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL)
    Ensayo clínico de fase II de MK 3475 (pembrolizumab) en sujetos con linfoma de Hodgkin clásico (LHc) recidivante o resistente al tratamiento (R/R)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    MK-3475 (pembrolizumab) in subjects with Classical Hodgkin Lymphoma
    MK 3475 (pembrolizumab) en sujetos con linfoma de Hodgkin clásico
    A.4.1Sponsor's protocol code numberMK3475-087
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck Sharp & Dohme Corp., filial de Merck & Co., Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co.Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme de España S.A.
    B.5.2Functional name of contact pointInvestigación Clínica
    B.5.3 Address:
    B.5.3.1Street AddressC/ Josefa Valcárcel, 38
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28027
    B.5.4Telephone number+34608373575
    B.5.5Fax number+34913210590
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePembrolizumab
    D.3.2Product code MK-3475
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.3Other descriptive nameAnti-PD-1 monoclonal antibody
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL)
    Linfoma de Hodgkin clásico (LHc) recidivante o resistente al tratamiento
    E.1.1.1Medical condition in easily understood language
    Hodgkin Lymphoma
    Linfoma de Hodgkin
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main 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
    E.2.2Secondary 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
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full 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.
    E.3Principal 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
    E.4Principal 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.
    E.5 End points
    E.5.1Primary 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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At each cycle and as clinically deemed
    En cada ciclo que se considere clínicamente
    E.5.2Secondary 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
    E.5.2.1Timepoint(s) of evaluation of this end point
    At each cycle and as clinically deemed
    En cada ciclo que se considere clínicamente
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other 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.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA38
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Russian Federation
    United Kingdom
    United States
    E.8.7Trial 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
    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).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 153
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 27
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 134
    F.4.2.2In the whole clinical trial 180
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-06-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-06-04
    P. End of Trial
    P.End of Trial StatusOngoing
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