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    Summary
    EudraCT Number:2017-000498-35
    Sponsor's Protocol Code Number:EORTC-1537-LYMG
    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:2019-06-24
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2017-000498-35
    A.3Full title of the trial
    Very early FDG-PET-response adapted targeted therapy for advanced Hodgkin lymphoma: a single-arm phase II study
    Adaptación del tratamiento selectivo para el linfoma de Hodgkin avanzado en función de una respuesta muy temprana en la TEP-FDG: estudio fase II de un solo grupo
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Very early FDG-PET-response adapted targeted therapy for advanced Hodgkin lymphoma: a single-arm phase II study
    Adaptación del tratamiento selectivo para el linfoma de Hodgkin avanzado en función de una respuesta muy temprana en la TEP-FDG: estudio fase II de un solo grupo
    A.3.2Name or abbreviated title of the trial where available
    COBRA
    A.4.1Sponsor's protocol code numberEORTC-1537-LYMG
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03517137
    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 SponsorEuropean Organisation for Research and Treatment of Cancer (EORTC)
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEORTC
    B.4.2CountryBelgium
    B.4.1Name of organisation providing supportMillennium Pharmaceuticals, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEuropean Organisation for Research and Treatment of Cancer (EORTC)
    B.5.2Functional name of contact pointClinical Operation Department
    B.5.3 Address:
    B.5.3.1Street AddressAvenue E. Mounier 83/11
    B.5.3.2Town/ cityBrussels
    B.5.3.3Post code1200
    B.5.3.4CountryBelgium
    B.5.4Telephone number+3227741542
    B.5.5Fax number+3227727063
    B.5.6E-mailregulatory@eortc.org
    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 Yes
    D.2.1.1.1Trade name Adcetris
    D.2.1.1.2Name of the Marketing Authorisation holderTakeda Pharma A/S
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/08/596
    D.3 Description of the IMP
    D.3.1Product nameBrentuximab vedotin
    D.3.2Product code SGN-35
    D.3.4Pharmaceutical form Powder for concentrate for solution for injection/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.3.8INN - Proposed INNBrentuximab vedotin
    D.3.9.1CAS number 914088-09-8
    D.3.9.3Other descriptive nameBRENTUXIMAB VEDOTIN
    D.3.9.4EV Substance CodeSUB32397
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    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.IMP: 2
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameAdriamycin
    D.3.4Pharmaceutical form Solution for injection/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.3.8INN - Proposed INNDOXORUBICIN
    D.3.9.1CAS number 23214-92-8
    D.3.9.3Other descriptive nameAdriamycin
    D.3.9.4EV Substance CodeSUB06391MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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.IMP: 3
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameVinblastine
    D.3.4Pharmaceutical form Solution for injection/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.3.8INN - Proposed INNVINBLASTINE
    D.3.9.1CAS number 865-21-4
    D.3.9.4EV Substance CodeSUB00052MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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.IMP: 4
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameDacarbazine
    D.3.4Pharmaceutical form Solution for injection/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.3.8INN - Proposed INNDACARBAZINE
    D.3.9.1CAS number 4342-03-4
    D.3.9.4EV Substance CodeSUB06882MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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.IMP: 5
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameCyclophosphamide
    D.3.4Pharmaceutical form Powder for solution for injection/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.3.8INN - Proposed INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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.IMP: 6
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameEtoposide
    D.3.4Pharmaceutical form Concentrate for 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.3.8INN - Proposed INNEtoposide
    D.3.9.3Other descriptive nameETOPOSIDE
    D.3.9.4EV Substance CodeSUB07337MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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.IMP: 7
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameDexamethasone
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDEXAMETHASONE
    D.3.9.3Other descriptive nameDexamathasone
    D.3.9.4EV Substance CodeSUB07017MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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
    Advanced stage Hodgkin Lymphoma
    Linfoma de Hodgkin avanzado
    E.1.1.1Medical condition in easily understood language
    Lymphoma
    Linfoma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10080208
    E.1.2Term Classical Hodgkin lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10020206
    E.1.2Term Hodgkin's disease
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10020243
    E.1.2Term Hodgkin's disease NEC
    E.1.2System Organ Class 10005329 - Blood and lymphatic system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLGT
    E.1.2Classification code 10025319
    E.1.2Term Lymphomas Hodgkin's disease
    E.1.2System Organ Class 10005329 - Blood and lymphatic system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10005329
    E.1.2Term Blood and lymphatic system disorders
    E.1.2System Organ Class 10005329 - Blood and lymphatic system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT results in improved efficacy while minimizing treatment toxicity in advanced stage HL patients treated with BV-containing regimens, BrAVD and BrECADD.
    This will be primarily assessed by modified progression-free survival.
    El objetivo principal de este ensayo es evaluar si la adaptación del tratamiento basada en los resultados de una tomografía de emisión de positrones/tomografía axial computarizada con fluorodesoxiglucosa (TEP/TAC-FDG) muy temprana produce una mejora de la eficacia, al tiempo que se minimiza la toxicidad del tratamiento en los pacientes con linfoma de Hodgkin (LH) en estadio avanzado tratados con regímenes que contienen brentuximab vedotina.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    • To assess the rate of FDG-PET negativity (Deauville score 1-3) after 1 cycle of BrAVD
    • To assess response according to Lugano Criteria at end of protocol treatment i.e. after chemotherapy and after radiotherapy (if administered), as defined by FDG-PET/CT
    • To assess the safety and tolerability of the different BV containing regimens
    • To assess the safety and tolerability of radiotherapy in the context of BrAVD and BrECADD
    • To assess efficacy in terms of PFS and OS
    Los objectivos secundarios son:
    - Evaluar la proporcion de TEP/TAC-FDG negativo (puntuacion Deauville 1-3)
    -Evaluar la respuesta segun Criterio Lugano despues del termino de tratamiento ej. despues de quemioterapia y antes de radioterapia (si admnistrada), como definido por TEP/TAC-FDG
    - Evaluar la seguridad y tolerabilidade a los diferientes regimenes con BV
    -Evaluar la seguridad y tolerabilidad a radioterapia en el contexto de BrDVD y BrECDDD
    -Evaluar la eficacia a respecto de Superviviencia sin progresion y Supervivencia general
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Previously untreated, histologically proven classical Hodgkin lymphoma;
    • Staged by PET with diagnostic-quality CT (i.v. contrast).
    - Clinical stages according to Lugano 2014 and based on FDG/PET CT:Stage IIB with large mediastinal mass > 1/3 max transverse diameter thorax and/or extranodal lesion(s) (GHSG)
    - Stage III - IV
    • Participation in translational research is mandatory and therefore patient must consent for it. The following material must be available:
    - Archival tumor tissue available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block);
    - To allow sequential sampling of blood during the course of the trial.
    • Age ≥18 and ≤60
    • WHO performance status 0-2
    • Patient demonstrates adequate organ function as defined in the protocol.
    • Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
    • Patients of childbearing / reproductive potential should use two birth control methods, as defined by the investigator, from the time of signing the informed consent form , and throughout the entire study and for 6 months after the last dose of treatment.
    • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
    • Absence of any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
    • Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
    • Linfoma de Hodgkin clásico confirmado histológicamente, sin tratamiento previo;
    • Estadificado mediante TEP con TAC de calidad diagnóstica (contraste i.v.).
    -Estadios clínicos según Lugano 2014 y basados en TEP/TAC-FDG: estadio IIB con gran masa mediastínica >1/3 del diámetro transversal máx. del tórax y/o una o varias lesiones extraganglionares (Grupo Alemán para el Estudio del Linfoma de Hodgkin [German Hodgkin Study Group, GHSG])
    - Estadio III - IV
    •La participación en la investigación traslacional es obligatoria y, por lo tanto, el paciente debe dar su consentimiento para ello. Debe estar disponible el siguiente material:

    - Tejido tumoral de archivo disponible (15 muestras de tejido sin teñir fijadas con formol e incluidas en parafina, montadas en portaobjetos con 3-aminopropiltrietoxisilano [APES] o en un bloque de tejido);
    - Permitir la obtención de muestras secuenciales de sangre durante el transcurso del ensayo.
    • Edad ≥18 y ≤60 años.
    • Estado general según la OMS de 0-2.
    • Paciente que muestre una funcionalidad orgánica adecuada como ejemplificado en el protocolo.
    • Las mujeres en edad fértil (MEF) deben obtener una prueba de embarazo en suero negativa dentro de las 72 horas previas a la primera dosis del tratamiento del estudio.
    • Las pacientes en edad fértil/con capacidad reproductiva deben utilizar dos métodos anticonceptivos establecidos por el investigador desde el momento de firmar el formulario de consentimiento informado, a lo largo de todo el estudio y hasta 6 meses después de la última dosis del tratamiento.
    •Las pacientes que estén en periodo de lactancia deben interrumpirlo antes de la primera dosis del tratamiento del estudio y hasta 6 meses después del último tratamiento del estudio.
    •Ausencia de cualquier afección médica, psicológica, familiar, sociológica o geográfica que pudiera potencialmente afectar al cumplimiento del protocolo del estudio y el calendario de seguimiento; estas afecciones deben comentarse con el paciente antes de llevar a cabo el registro en el ensayo.
    •Antes del registro del paciente, se debe dar el consentimiento informado por escrito conforme a las ICH/BPC y a los reglamentos nacionales/locales.
    E.4Principal exclusion criteria
    • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
    • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
    • Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 5.0
    • Any of the following cardiovascular conditions or values:
    - within 6 months before registration:
    • A left-ventricular ejection fraction <50%
    • New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D).
    • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
    • symptomatic coronary heart disease (stable angina pectoris is allowed)
    • severe uncontrolled hypertension defined as blood pressure (BP) >150/100 mmHg despite optimal antihypertensive treatment
    - within 2 years before registration:
    • Myocardial infarction
    • Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 % or a fasting blood sugar > 200 mg/dL).
    • Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration.
    • Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients).
    Note: HBsAg-/HBV DNA – patients are eligible; patients who are seropositive due to vaccination are eligible
    • Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix , nonmelanoma skin cancer.
    • Previous treatment with anti CD30 antibodies
    • Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs. Refer to Summary Product Characteristics for list of excipients.
    • Concurrent anti-cancer treatment or use of any investigational agent(s)
    • Antecedentes conocidos de enfermedad cerebral o meníngea (por LH o cualquier otra etiología), incluidos signos o síntomas de leucoencefalopatía progresiva multifocal.
    • Enfermedad neurológica sintomática que afecte a las actividades normales de la vida diaria o que requiera medicación.
    • Neuropatía periférica sensorial o motora superior o igual a grado 2 de acuerdo con los criterios CTCAE, versión 5.0.
    • Cualquiera de las siguientes afecciones o valores cardiovasculares:
    Dentro de los 6 meses anteriores al registro:
    • Fracción de eyección ventricular izquierda <50 % (en el momento del registro).
    • Insuficiencia cardíaca de clase III o IV según la Asociación del Corazón de Nueva York (New York Heart Association, NYHA).
    • Indicios de afecciones cardiovasculares en curso no controladas, como arritmias cardíacas, insuficiencia cardíaca congestiva (ICC), angina de pecho o indicios electrocardiográficos de isquemia aguda o de anomalías activas del sistema de conducción.
    • Cardiopatía coronaria sintomática (se permite la angina de pecho estable).
    • Hipertensión grave no controlada, definida como presión arterial (PA) >150/100 mmHg a pesar de un tratamiento antihipertensivo óptimo.
    Dentro de los 2 años anteriores al registro:
    • Infarto de miocardio.
    • Pacientes con diabetes mellitus mal controlada (HbA1c >7,5 % o glucemia en ayunas >200 mg/dl).
    • Cualquier infección vírica, bacteriana o fúngica sistémica activa que requiera antibióticos sistémicos dentro de las 2 semanas anteriores al registro en el estudio.
    • Infección conocida por VIH, hepatitis C crónica activa, positividad para el VHB (pacientes HBsAg+; pacientes HBsAg-/HBcAb+/ADN VHB+).
    Nota: los pacientes HBsAg-/ADN VHB- son aptos; los pacientes seropositivos por estar vacunados son aptos.
    • Neoplasias malignas simultáneas o anteriores en los últimos 5 años, a excepción del carcinoma cervicouterino in situ y del cáncer de piel no melanoma que hayan sido tratados debidamente.
    • Tratamiento previo con anticuerpos anti-CD30.
    • Hipersensibilidad conocida a cualquier excipiente incluido en la formulación de brentuximab vedotina y de otros fármacos del estudio.
    • Tratamiento antineoplásico simultáneo o uso de cualquier fármaco en investigación.
    E.5 End points
    E.5.1Primary end point(s)
    Modified progression-free survival rate at 2 years after start of treatment (2yr-mPFS).
    The following are considered events for the primary endpoint: progression/relapse; start of new treatment for cHL when not in CR after completing protocol treatment; death from any cause.
    Tasa de supervivencia sin progresión modificada a los 2 años (SSPm-2a), estimada a partir de la curva de Kaplan Meier de SSP modificada (SSPm). La SSP modificada (SSPm) se define como el periodo transcurrido entre la fecha de inicio del tratamiento y la fecha de la primera de las siguientes circunstancias:
    • Progresión de la enfermedad (PE);
    • Inicio de un nuevo tratamiento para el LHc sin tener respuesta completa RC) al final del tratamiento del estudio;
    • Muerte debida a cualquier causa.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Modified progression-free survival rate at 2 years (2yr-mPFS). Modified PFS is defined as the time interval between the treatment start date and the date of the first of:
    • Progressive disease (PD)
    • Start of new treatment for cHL when not in CR at the end of protocol treatment; in this case, the date of mPFS is the date of the FDG-PET/CT scan at the end of protocol treatment. Switching therapy prior to end of protocol treatment for reasons other than PD is not considered an event for mPFS. "End of protocol treatment" refers to completion of the planned protocol treatment with no more than 1 missed cycle, including radiotherapy on PET positive lesions if administered
    • Death due to any cause
    Patients without any of these events will be censored at the last response assessment date.
    • Progresión de la enfermedad (PE);
    • Inicio de un nuevo tratamiento para el LHc sin tener respuesta completa RC) al final del tratamiento del estudio; en este caso, la fecha de SSPm será la fecha de la exploración por TEP/TAC-FDG al final del tratamiento del estudio. El cambio de tratamiento antes de acabar el tratamiento del estudio por motivos distintos a la PE no se considera un acontecimiento para la SSPm. El “final del tratamiento del studio” hace referencia al término del tratamiento previsto con no más de 1 ciclo omitido, lo que incluye la radioterapia en las lesiones positivas según la TEP, si se administra.
    • Muerte debida a cualquier causa.
    • Los pacientes que no presenten ninguno de estos acontecimientos se censurarán en la fecha de la última evaluación de la respuesta.
    E.5.2Secondary end point(s)
    The secondary endpoints are:
    • Proportion of patients with negative FDG-PET after 1 cycle of BrAVD (central assessment)
    • Response rate according to Lugano Criteria at end of protocol treatment i.e. after chemotherapy and after radiotherapy (if administered),
    • Progression-free survival (where progression, relapse and death from any cause are considered events).
    • Overall survival
    • Safety and tolerability
    • Response rate according to RECIL 2017
    Los criterios de valoración secundarios:
    • Proporción de pacientes con resultados negativos en la TEP-FDG después de 1 ciclo de BrDVD.
    • Tasa de respuesta según los Criterios de Lugano al final del tratamiento del protocolo, es decir, tanto después de la quimioterapia como después de la radioterapia (si se administra), en el mes 24 después de iniciar el tratamiento.
    • Supervivencia sin progresión (donde la progresión, la recaída y la muerte por cualquier causa se consideran acontecimientos).
    • Supervivencia general.
    • Tasa de respuesta según RECIL 2017.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Until death
    Hasta la muerte
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Treatment strategy based on FDG-PET results
    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.7.1.3.1Other 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.8.2.4Number of treatment arms in the trial1
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    Belgium
    Croatia
    Denmark
    Egypt
    France
    Netherlands
    Poland
    Portugal
    Slovakia
    Spain
    E.8.7Trial 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
    End of study occurs when all of the following criteria have been satisfied:
    1. Thirty days after all patients have stopped protocol treatment
    2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
    3. The database has been fully cleaned and frozen for this analysis
    Final de estudio ocurre cuando todos los seguintes puntos estan completos:
    1. Treinta dias despues de todos los pacientes teneren parado el tratamiento
    2. El estudio esta pronto para analisis del criterio de valoracion prinicpal como definido en el protocolo
    3. La base de datos esta limpia y congelada para analisis
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months6
    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: 150
    F.1.3Elderly (>=65 years) No
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 140
    F.4.2.2In the whole clinical trial 150
    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)
    According to the discretion of the treating physician.
    A determinar por el medico investigador
    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 Decision2019-06-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-05-02
    P. End of Trial
    P.End of Trial StatusOngoing
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