Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2012-004915-30
    Sponsor's Protocol Code Number:HOVON-113-MSC
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2015-03-11
    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 number2012-004915-30
    A.3Full title of the trial
    Treatment of severe steroid-refractory acute GvHD with mesenchymal stromal cells. A phase III, randomized double-blind multi-center HOVON study.
    Tratamiento de la enfermedad injerto contra huésped aguda, refractaria a tratamiento corticoideo con Células Stem Mesenquimales. Estudio fase III randomizado, doble-ciego multicéntrico del grupo HOVON
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Treatment of severe steroid-refractory acute GvHD with mesenchymal stromal cells.
    Tratamiento de la enfermedad injerto contra huésped aguda refractaria a tratamiento corticoideo con Células Stem Mesenquimales
    A.3.2Name or abbreviated title of the trial where available
    HOVON 113 MSC
    A.4.1Sponsor's protocol code numberHOVON-113-MSC
    A.5.4Other Identifiers
    Name:NL42497.000.12Number:NTR4227
    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 SponsorHOVON Foundation
    B.1.3.4CountryNetherlands
    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 supportDutch Cancer Society
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportSanquin Blood Supply
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportEuropean Union (Horizon 2020, grant agreement n 643580)
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHOVON Data Center
    B.5.2Functional name of contact pointHDC
    B.5.3 Address:
    B.5.3.1Street Address's-Gravendijkwal 230
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015 CE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31(0)107041560
    B.5.5Fax number+31(0)107041028
    B.5.6E-mailhdc@erasmusmc.nl
    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 nameCélulas mesenquimales troncales adultas alogénicas de médula ósea expandidas criopreservadas ex vivo
    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 INNCélulas mesenquimales troncales adultas alogénicas de médula ósea expandidas criopreservadas ex vivo
    D.3.9.1CAS number n.a.
    D.3.9.2Current sponsor coden.a.
    D.3.9.3Other descriptive nameAllogeneic bone marrow stem adult mesenchymal cells expanded ex-vivo criopreserved
    D.3.9.4EV Substance CodeSUB27304
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number1000000
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Graft Versus Host Disease
    Enfermedad injerto contra huésped
    E.1.1.1Medical condition in easily understood language
    Graft Versus Host Disease
    Enfermedad injerto contra huésped
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10066260
    E.1.2Term Acute graft versus host disease
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10068908
    E.1.2Term AGVHD
    E.1.2System Organ Class 10021428 - Immune 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
    To improve the response rate to treatment of acute GvHD grade II-IV (with gut and/or liver involvement) by early addition of MSC to standardized second line treatment.
    Mejorar la tasa de respuesta al tratamiento de la EICH aguda grados II-IV (con afectación de hígado y/o intestino) mediante la adición precoz de CSM al tratamiento estándar de segunda línea
    E.2.2Secondary objectives of the trial
    * To study the safety of MSC addition to second line treatment
    * To assess the overall survival
    * To assess the progression-free survival
    * To reduce the time required for continued pharmacological immune suppression
    * To assess the incidence of severe bacterial, viral and fungal infections
    * To assess the incidence and severity of chronic GvHD
    * To evaluate the quality of life of patients treated with MSC in comparison with controls up to two years after MSC treatment
    * To develop a score by means of clinical and laboratory parameters that allows for identification of patients with acute GvHD that will respond to MSC treatment
    •Estudiar la seguridad de la adición de CSM a la segunda línea de tratamiento
    •Evaluar la supervivencia global.
    •Evaluar la Supervivencia Libre de Progresión.
    •Disminuir el tiempo en el que es necesaria una inmunosupresión farmacológica continua
    •Evaluar la incidencia de las infecciones bacterianas, víricas y fúngicas graves.
    •Evaluar la incidencia y gravedad de la EICH crónica
    •Evaluar la calidad de vida del paciente en tratamiento con CSM en comparación 
con controles hasta los 2 años tras el tratamiento con CSM.
    •Desarrollar una puntuación (score) de parámetros clínicos y de laboratorio que permita la identificación de 
pacientes con EICH aguda que responderán al tratamiento con CSM
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    * Grade II-IV acute GvHD with gut and/or liver involvement, confirmed by histology of involved tissues (in case of gut and liver involvement histology of either one of these tissues is considered sufficient); N.B. if the patient is otherwise eligible but histological confirmation at randomization is lacking, the principal investigator should be contacted.*
    * Non-responsive to consecutive systemic treatment with steroids at a dose of 2 mg/kg and a calcineurin-inhibitor at therapeutic trough levels, defined as:
    - progressive disease or mixed response after 5-6 days of treatment.
    - stage 4 GvHD of gut and/or liver after 5-6 days treatment and:
    · significant deterioration of clinical parameters (gut) OR
    · increase of serum total bilirubin levels in umol/L (liver)
    (not attributable to other causes than acute GvHD)
    - progressive disease after initial partial response of maximal 1 grade after 5-7 days of treatment
    - stable disease after 7 days of treatment
    See appendix A for response criteria
    * Any age
    * Lansky / Karnofsky score of ≥20;
    * Signed informed consent by the patient and/or parent(s) or legal guardian(s).
    * EICH aguda grados II-IV con afectación de hígado y/o intestino, confirmado por histología del tejido/s afectado/s (en caso de afectación del intestino y del hígado la histología de uno de ellos se considera suficiente); N.B. si el paciente es elegible pero no tiene confirmación histológica, se contactará con el investigador principal
    *Ausencia de respuesta al tratamiento sistémico secuencial con esteroides a dosis de 2 mg/kg e inhibidores de calcineurina en rango terapeútico, definido como:
    -enfermedad en progresión o respuesta mixta tras 5-6 días de tratamiento
    -EICH aguda grado IV, de hígado y/o intestino tras 5-6 días tratamiento y:
    · deterioro significativo de los parámetros clínicos (intestinal) o
    · incremento de los niveles totales de bilirrubina en suero en umol/L (hígado)
    (no atribuible a otras causas que no sean EICH aguda)
    -enfermedad en progresión tras una primera respuesta parcial (RP) de grado máximo 1, tras 5-7 días de tratamiento
    -enfermedad estable después de 7 de tratamiento
    Ver apéndice A para criterios respuesta
    *Cualquier edad
    *Puntuación de Lansky/ Karnofsky ≥20
    *Consentimiento informado firmado por el paciente y/o progenitor o representante legal.
    E.4Principal exclusion criteria
    * In Spain only adult patients will be included
    * Use of prophylactic MMF or Myfortic ? 6 days prior to development of acute GvHD ;
    * Systemic treatment for acute GvHD other than steroids and a calcineurin inhibitor (budesonide is considered a local treatment);
    * Pre-treatment with steroids ? 1 mg/kg for more than 3 days prior to initiation of steroids at a dose of 2 mg/kg for the treatment of acute GvHD;
    * Previous treatment with advanced therapy medicinal products (ATMP) potentially interfering with the endpoints of this study; N.B. if the patient has previously been treated with ATMP , the principal investigator should always be contacted prior to registration*.
    * Progressive or relapsing malignant disease in case of NHL, HL, CLL, MM, and ≥ 5% blasts in the bone marrow in case of AML, ALL, CML;
    * Requiring ventilator or vasopressor support;
    * Poor performance not expected to survive 14 days;
    * Known seropositivity of HIV, Hepatitis B and C, HTLV;
    * Known uncontrolled toxicity for DMSO;
    * Known anaphylactic reaction to penicillin or streptomycin;
    * Known pregnancy;
    * Any psychological, familial, sociological and /or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
    * En España solo se incluirán pacientes adultos
    * Uso de MMF (micofenolato mofetilo) profiláctico o Myfortic ≤ 6 días antes del desarrollo de EICH aguda
    * Tratamiento sistémico para EICH aguda, diferente de corticoesteriodes e inhibidor de calcineurina (budesonida se considera tratamiento local).
    * Pretratamiento con esteroide ≥ 1 mg/kg durante más de tres días antes de iniciar esteroide a dosis de 2mg/kg para el tratamiento de EICH aguda
    * Tratamiento previo con productos de terapia avanzada (ATMP) que potencialmente interfieran con el objetivo de este estudio; N.B. si el paciente ha sido previamente tratado con ATMP, el investigador principal deberá ser consultado antes del registro.

    * Enfermedad progresiva o en recaída en caso de LNH, LH, LLC, MM y ≥ 5% blastos en médula ósea, en caso de LMA, LLA, LMC.

    * Paciente que requiera tratamiento con ventilación mecánica o soporte vasopresor.
    * Paciente con mal estado general con esperanza de vida inferior a 14 días.

    * Seropositividad para VIH, Hepatitis B y C, HTLV;

    * Toxicidad no controlada al DMSO.

    * Reacción anafiláctica a la penicilina o estreptomicina.

    * Embarazo conocido

    * Cualquier condición, potencialmente complicada, en cuanto a situación psicológica, familiar, sociológica y/o geográfica.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients responding to treatment of acute GvHD grade II-IV (with gut and/or liver involvement) at day 29.
    Proporción de pacientes que responden al tratamiento de EICH aguda grado II-IV (con afectación de intestino y/o hígado) a día 29
    E.5.1.1Timepoint(s) of evaluation of this end point
    Two interim analyses will take place after inclusion of 33% and 67% of patients These results will be reviewed confidentially by the DSMB.
    Final analysis will take place when the relevant data of all patients are available
    Se realizarán dos análisis intermedios después de la inclusion de 33% y 67% de pacientes, respectivamente. Estos resultados serán revisados confidencialmente or el DSMB (Data Safety Monitoring Board-Comité de Monitorización de Datos de Seguridad). El análisis final tendrá lugar cuando los datos relevantes de todos los pacientes estén disponibles
    E.5.2Secondary end point(s)
    - Overall Survival
    - Progression-free survival
    - Duration of acute GvHD response
    - Time without systemic immunosuppression.
    - Cumulative incidence of non-relapse mortality
    - Adverse events
    - Incidence of chronic GvHD
    - Quality of life
    - Immununological monitoring including monitoring of absolute T-cell subsets, B-cells, NK-cells as well as biomarkers of acute GvHD
    -Supervivencia global
    -Supervivencia libre de progresión
    -Duración de la respuesta a EICH aguda
    -Tiempo sin inmunosupresión sistémica
    -Incidencia acumulada de mortalidad sin-recaída
    -Acontecimientos adversos
    -Incidencia de EICH crónica
    -Calidad de vida
    -Control inmunológico incluyendo seguimiento de subpoblaciones de células-T, células NK así como biomarcadores de EICH aguda.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Two interim analyses will take place after inclusion of 33% and 67% of patients These results will be reviewed confidentially by the DSMB.
    Final analysis will take place when the relevant data of all patients are available
    Se realizarán dos análisis intermedios después de la inclusion de 33% y 67% de pacientes. Estos resultados serán revisados confidencialmente or el DSMB (Data Safety Monitoring Board-Comité de Monitorización de Datos de Seguridad). El análisis final tendrá lugar cuando los datos relevantes de todos los pacientes estén disponibles
    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 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA9
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    Última Visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years12
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years12
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 15
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 1
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 9
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 125
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    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)
    Treatment after end of protocol treatment is at the discretion of the treating physician. For children, this may include MSC treatment.
    El tratamiento tras el final del tratamiento del ensayo es a criterio del médico responsable. Para pacientes pediátricos, éste puede incluir células mesenquimales (se recuerda que en España no se incluirán pacientes pediátricos)
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation HOVON Foundation
    G.4.3.4Network Country Netherlands
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-05-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-08-20
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 07:05:40 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA