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    Summary
    EudraCT Number:2016-002347-41
    Sponsor's Protocol Code Number:CA209-744
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-17
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2016-002347-41
    A.3Full title of the trial
    Risk-based, response-adapted, Phase II open-label trial of nivolumab + brentuximab vedotin (N + Bv) for children, adolescents, and young adults with relapsed/refractory (R/R) CD30 + classic Hodgkin lymphoma (cHL) after failure of first-line therapy, followed by brentuximab + bendamustine (Bv + B) for participants with a suboptimal response. CheckMate 744: CHECKpoint pathway and nivolumab clinical Trial Evaluation
    Sperimentazione in aperto di Fase II, basata sul rischio, adattata alla risposta su nivolumab+brentuximab vedotin (N+Bv) seguita da brentuximab vedotin+bendamustina (Bv+B) per i partecipanti con risposta sub-ottimale, per bambini, adolescenti e giovani adulti con linfoma di Hodgkin classico (cHL) CD30+ recidivante/refrattario (R/R) dopo il fallimento della terapia di prima linea. (CheckMate 744: CHECKpoint pathway and nivolumab clinical Trial Evaluation)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Nivolumab + Brentuximab Vedotin in Children, Adolescents, and Young Adults With Classic Hodgkin Lymphoma (cHL) After Failure of First Line Therapy, Followed by Brentuximab Vedotin + Bendamustine for Participants With a Suboptimal Response (CheckMate 744)
    Studio di nivolumab+brentuximab vedotin (N+Bv) seguita da brentuximab vedotin+bendamustina (Bv+B) per i partecipanti con risposta sub-ottimale, per bambini, adolescenti e giovani adulti con linfoma di Hodgkin classico (cHL) dopo il fallimento della terapia di prima linea. (CheckMate 744)
    A.3.2Name or abbreviated title of the trial where available
    CheckMate 744
    CheckMate 744
    A.4.1Sponsor's protocol code numberCA209-744
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02927769
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1183-3601
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/004/2017
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
    B.1.3.4CountryBelgium
    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 supportBristol-Myers Squibb International Corporation
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointGCT-SU
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande, 4
    B.5.3.2Town/ cityBraine-l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.4Telephone number0000000
    B.5.5Fax number0000000
    B.5.6E-mailclinical.trials@bms.com
    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 Opdivo
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    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 nameNivolumab - 10 ml vial - clinico
    D.3.2Product code [BMS-936558]
    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.3.8INN - Proposed INNNIVOLUMAB
    D.3.9.1CAS number 946414-94-4
    D.3.9.2Current sponsor codeBMS-936558-01
    D.3.9.3Other descriptive nameBMS-936558, MDX1106, ONO-4538
    D.3.9.4EV Substance CodeSUB32944
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.2.1.1.1Trade name ADCETRIS
    D.2.1.1.2Name of the Marketing Authorisation holderSeattle Genetics
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameNA
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Powder 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 INNbrentuximab vedotin
    D.3.9.1CAS number 914088-09-8
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameBRENTUXIMAB VEDOTIN
    D.3.9.4EV Substance CodeSUB32397
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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.2.1.1.1Trade name Bendamustine HEXAL
    D.2.1.1.2Name of the Marketing Authorisation holderHexal AG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameNA
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Powder 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 INNBENDAMUSTINE HYDROCHLORIDE
    D.3.9.1CAS number 3543-75-7
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive namend
    D.3.9.4EV Substance CodeSUB00696MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.2.1.1.1Trade 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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNA
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Powder 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 INNBRENTUXIMAB VEDOTIN
    D.3.9.1CAS number 914088-09-8
    D.3.9.2Current sponsor codend
    D.3.9.3Other descriptive nameBRENTUXIMAB VEDOTIN
    D.3.9.4EV Substance CodeSUB32397
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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.2.1.1.1Trade name Bendamustine cell pharm
    D.2.1.1.2Name of the Marketing Authorisation holderSTADAPHARM GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameNA
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Powder 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 INNbendamustina idrocloruro
    D.3.9.1CAS number 3543-75-7
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeSUB00696MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.2.1.1.1Trade name Opdivo (100 mg/10 ml)
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    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 nameNIVOLUMAB - 10ml vial - COMMERCIAL
    D.3.2Product code [BMS-936558]
    D.3.4Pharmaceutical form Solution for injection
    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 INNnivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.2Current sponsor codeBMS-936558-01
    D.3.9.3Other descriptive nameBMS-936558, MDX1106, ONO-4538
    D.3.9.4EV Substance CodeSUB32944
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.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/refractory (R/R) CD30 + classic Hodgkin lymphoma (cHL)
    linfoma di Hodgkin classico (cHL) CD30+ recidivante/refrattario (R/R)
    E.1.1.1Medical condition in easily understood language
    Hodgkin Disease
    Malattia di Hodgkin
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    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.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - R1 (Low Risk) Cohort: To describe event-free survival (EFS) rate at 3 years, as assessed by blinded independent central review (BICR).

    - R2 (Standard Risk) Cohort: to describe the complete metabolic response (CMR) rate prior to HDCT/ASCT by BICR, using Lugano 2014 response criteria
    - Coorte R1 (a basso rischio): descrivere il tasso di sopravvivenza libera da eventi (event-free survival, EFS) a 3 anni, in base alla valutazione del comitato centrale indipendente per la revisione in cieco (blinded independent central review, BICR).
    - Coorte R2 (rischio standard): descrivere il tasso di risposta metabolica completa (CMR) prima dell’HDCT/ASCT in base alla valutazione del BICR, secondo i criteri di valutazione della risposta Lugano 2014.
    E.2.2Secondary objectives of the trial
    - To assess overall response rate (ORR) (CMR + partial metabolic response [PMR]) using Lugano 2014 criteria of the low risk and standard risk cohorts following 4 cycles of nivolumab and brentuximab vedotin by BICR
    - To assess PFS rate at 3 years by BICR using Lugano 2014 criteria
    - Duration of Response (DOR) will be evaluated for those participants who achieved PMR or CMR by BICR as well as for those participants who achieved CMR by BICR prior to IFRT in the low risk cohort and for those participants who achieved CMR prior to HDCT/ASCT in the standard risk
    cohort
    - To describe the toxicity of nivolumab + brentuximab in combination in pediatric and young adult participants with relapsed or refractory classical Hodgkin's lymphoma (cHL) after failure of first-line treatment.
    -To evaluate efficacy as assessed by investigators using LUGANO (2014) response criteria.
    -Tasso di risposta globale (ORR) (CMR+ PMR) secondo i criteri Lugano 2014 per le coorti a basso rischio e a rischio standard dopo 4 cicli di nivo e brentuximab vedotin in base alla valutazione del BICR.
    -Tasso di PFS a 3 anni in base alla valutazione del BICR secondo i criteri Lugano 2014.
    -La durata della risposta (DOR) sarà valutata per quei partecipanti che hanno raggiunto una PMR o una CMR in base alla valutazione del BICR così come per quei partecipanti che hanno raggiunto una CMR in base alla valutazione del BICR prima della
    IFRT nella coorte a basso rischio e per quei partecipanti che hanno raggiunto una CMR prima dell’HDCT/ASCT nella coorte a rischio standard.
    -Valutare la tossicità della combinazione nivo+brentuximab nei partecipanti pediatrici e giovani adulti con cHL dopo il fallimento del trattamento di prima linea.
    -Valutare l’efficacia in base alla valutazione degli sperimentatori utilizzando i criteri di valutazione della risposta Lugano 2014
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Pharmacogenetics
    Version: N/A
    Date: 23/09/2016
    Title: N/A
    Objectives: Retention of sample collection for additional research is mandatory for all participants, except where prohibited by local laws or regulations. This protocol will include residual sample storage for additional research.
    For additional details, please refer to section 9.8.3 the original protocol dated 23-Sep-2016


    Pharmacogenomics
    Version: N/A
    Date: 23/09/2016
    Title: N/A
    Objectives: Retention of sample collection for additional research is mandatory for all participants, except where prohibited by local laws or regulations. This protocol will include residual sample storage for additional research.
    For additional details, please refer to section 9.8.3 the original protocol dated 23-Sep-2016

    Farmacogenetica
    Versione: N/A
    Data: 23/09/2016
    Titolo: N/A
    Obiettivi: La riserva di raccolta di campioni per la ricerca addizionale è obbligatoria per tutti i pazienti eccetto dove sia proibita dalle leggi o dai regolamenti locali. Questo protocollo includerà la conservazione di campioni residui per la ricerca addizionale. Per maggiori dettagli per favore fare riferimento alla sezione 9.8.3 del protocollo originale datato 23 Settembre 2016

    Farmacogenomica
    Versione: N/A
    Data: 23/09/2016
    Titolo: N/A
    Obiettivi: La riserva di raccolta di campioni per la ricerca addizionale è obbligatoria per tutti i pazienti eccetto dove sia proibita dalle leggi o dai regolamenti locali. Questo protocollo includerà la conservazione di campioni residui per la ricerca addizionale. Per maggiori dettagli per favore fare riferimento alla sezione 9.8.3 del protocollo originale datato 23 Settembre 2016
    E.3Principal inclusion criteria
    • Classic Hodgkin Lymphoma (cHL), relapsed or refractory
    • Minimal limitation on activities of daily living as measured by Karnofsky = 50 for participants > 16 years of age or Lansky = 50 for participants = 16 years of age.
    • One prior anti-cancer therapy that did not work
    - linfoma di Hodgkin classico (cHL) recidivante o refrattario
    - limitazioni minime nello svolgimento delle attività quotidiane misurate, per il pazienti > 16 anni, secondo la scala Karnofsky (punteggio maggiore /= 50) e per i pazienti minore/= 16 anni 50 secondo la scala Lansky (punteggio maggiore/= 50)
    - fallimento di una prima linea di trattamento
    E.4Principal exclusion criteria
    • Active, known, or suspected autoimmune disease or infection
    • Active cerebral/meningeal disease related to the underlying malignancy
    • More than one line of anti-cancer therapy or no treatment at all
    • Received a stem cell transplant for Hodgkin Lymphoma and/or a solid organ transplant
    • Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
    • Malattia autoimmune o infezione attiva, nota o sospetta
    • Malattia cerebrale/meningeale attiva correlata con la patologia in studio
    • Più di una linea di terapia anti-cancro o nessun trattamento precedente
    • Precedente trapianto di cellule staminali per il Linfoma di Hodgkin e/o trapianto d’organo
    • Precedente trattamento con qualsiasi farmaco che abbia come target i meccanismi di costimolazione delle cellule T (come gli inibitori dei checkpoint)
    E.5 End points
    E.5.1Primary end point(s)
    - Event Free Survival (EFS) ; Low Risk Group. Based on blinded
    independent central review (BICR)
    - Complete Metabolic Response (CMR) prior to RT; Low Risk Group. The
    CMR rate is defined as the proportion of all response-evaluable
    participants who, assessed by the BICR, achieve best response of CMR
    using Lugano 2014 criteria.
    - Complete Metabolic Response (CMR) Rate; Standard Risk Group. This is
    the rate prior to high-dose chemotherapy followed by autologous stem
    cell transplant (HDCT/ASCT) based on the blinded independent central
    review (BICR).
    - Coorte R1 (a basso rischio): Tasso di sopravvivenza libera da eventi (event-free survival, EFS) in
    base alla valutazione del comitato centrale indipendente per la revisione in cieco (blinded independent central review, BICR).
    - Coorte R1 (a basso rischio): Tasso di risposta metabolica completa (CMR) precedente alla RT. Il tasso di CMR è definito come la
    porzione di tutti i pazienti con risposta valutabile che raggiungano come miglior risposta la CMR valutata dal BICR utilizzando i
    criteri di valutazione della risposta Lugano 2014.
    - Coorte R2 (rischio standard): Tasso di Risposta Metabolica Completa (CMR) prima della chemioterapia ad alto dosaggio seguita
    da trapianto di cellule staminali autologhe (HDCT/ASCT) in base alla valutazione del BICR, secondo i criteri di valutazione della
    risposta Lugano 2014.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 5 years
    Fino a 5 anni
    E.5.2Secondary end point(s)
    • Overall Response Rate (ORR)
    Based on blinded independent central review (BICR)
    • Progression Free Survival Rate (PFSR)
    Based on the blinded independent central review (BICR)
    • Duration of Response (DOR)
    Based on the blinded independent central review (BICR)
    • Incidence of serious and non-serious adverse events of nivolumab
    (BMS-936558) and brentuximab when given in combination
    • Incidence of clinically significant abnormalities in general laboratory
    tests of nivolumab (BMS-936558) and brentuximab when given in
    combination. Hematology, Chemistry and Urinalysis
    • Incidence of clinically significant vital sign measurements of
    nivolumab (BMS-936558) and brentuximab when given in combination.
    Temperature, Blood Pressure and Heart Rate
    •Complete Metabolic Response (CMR)
    •Complete Metabolic Response (CMR) rate at any time prior to radiation
    therapy
    •EFS: Low Risk Group. Based on investigator assessments
    •ORR: All participants, based on investigator assessments, after 4 cycles
    of nivolumab + brentuximab vedotin treatment
    •PFSR:All participants, based on investigator assessments
    •DOR: All participants, based on investigator assessments
    - Tasso di risposta globale (overall response rate ORR) in base alla valutazione del comitato
    centrale indipendente per la revisione in cieco (blinded independent central review, BICR)
    - Tasso di sopravvivenza libera da progressione (Progression Free Survival Rate, PFSR) in base alla valutazione del comitato
    centrale indipendente per la revisione in cieco (blinded independent central review, BICR)
    - Durata della risposta (duration of response, DOR) in base alla valutazione del comitato centrale indipendente per la revisione in
    cieco (blinded independent central review, BICR)
    - Incidenza di Eventi Avversi seri o non seri per Nivolumab (BMS-936558) e Brentuximab vedotin quando somministrati in
    combinazione.
    - Incidenza di anormalità clinicamente significative nei test di laboratorio generali per Nivolumab (BMS-936558) e Brentuximab
    vedotin quando somministrati in combinazione.
    - Incidenza di rilevazioni clinicamente significative dei parametri vitali per Nivolumab (BMS-936558) e Brentuximab vedotin quando
    somministrati in combinazione. Temperatura Pressione Sanguigna e Frequenza Cardiaca.
    - Risposta metabolica completa (CMR)
    - Tasso di Risposta metabolica completa (CMR) in qualsiasi momento prima della radioterapia
    - EFS: gruppo a basso rischio. Secondo la valutazione dello sperimentatore
    - ORR: tutti i partecipanti, secondo la valutazione dello sperimentatore, dopo 4 cicli di trattamento con nivolumab+brentuximab vedotin
    - PFSR: tutti i partecipanti, secondo la valutazione dello sperimentatore
    - DOR: tutti i partecipanti, secondo la valutazione dello sperimentatore
    E.5.2.1Timepoint(s) of evaluation of this end point
    - ORR: Up to 12 weeks
    - Others: Up to 5 years
    -ORR: Fino a 12 settimane
    - Gli altri: Fino a 5 anni
    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 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.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 No
    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 trial2
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Czechia
    France
    Germany
    Ireland
    Italy
    Netherlands
    Poland
    Spain
    United Kingdom
    United States
    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
    LVLS (Once participants reach the survival follow-up phase, either in-person visits or documented telephone calls/email correspondence to assess the participant’s status are acceptable)
    La conclusione della sperimentazione è definita come l’ultima procedura effettuata per l’ultimo soggetto.
    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 months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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 Yes
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 4
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 24
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 52
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Assents are allowed since this is a pediatric study
    Gli assensi sono permessi considerando che si tratta di uno studio pediatrico
    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 40
    F.4.2.2In the whole clinical trial 80
    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)
    At the end of the study, BMS will not continue to provide BMS-supplied study treatment to participants/investigators unless BMS chooses to extend the study. The investigator should ensure that the participant receives appropriate standard of care.
    Al termine dello studio BMS non continuerà a fornire i trattamenti di studio ai soggetti partecipanti/sperimentatori a meno che BMS decida di estendere lo studio. Lo sperimentatore dovrà assicurarsi che i soggetti partecipanti ricevano terapia standard appropriata.
    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 Decision2017-03-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-01-31
    P. End of Trial
    P.End of Trial StatusOngoing
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