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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39587   clinical trials with a EudraCT protocol, of which   6490   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).
     
    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:2016-000259-28
    Sponsor's Protocol Code Number:54179060LYM3003
    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:2016-04-19
    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 number2016-000259-28
    A.3Full title of the trial
    A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma.
    Uno studio randomizzato, in aperto, sulla sicurezza e l'efficacia di ibrutinib in pazienti pediatrici e giovani adulti con linfoma non Hodgkin a cellule B mature recidivante o refrattario.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma
    Uno studio sulla sicurezza e l’efficacia di Ibrutinib in pazienti pediatrici e giovani adulti con linfoma non Hodgkin a cellule B mature recidivante o refrattario
    A.4.1Sponsor's protocol code number54179060LYM3003
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/252/2015
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorJanssen-Cilag International NV
    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 supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag International NV
    B.5.2Functional name of contact pointClinical Registry Group
    B.5.3 Address:
    B.5.3.1Street AddressArchimedesweg 29
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 CM
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+3171524 21 66
    B.5.5Fax number+3171524 21 10
    B.5.6E-mailClinicalTrialsEU@its.jnj.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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMA/OD/116/13
    D.3 Description of the IMP
    D.3.1Product nameIbrutinib
    D.3.2Product code JNJ-54179060
    D.3.4Pharmaceutical form Capsule, hard
    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 INNIbrutinib
    D.3.9.1CAS number 936563-96-1
    D.3.9.2Current sponsor codeJNJ-54179060
    D.3.9.3Other descriptive nameIBRUTINIB
    D.3.9.4EV Substance CodeSUB120863
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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: 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 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 nameIbrutinib
    D.3.2Product code JNJ-54179060
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation Yes
    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 INNIbrutinib
    D.3.9.1CAS number 936563-96-1
    D.3.9.2Current sponsor codeJNJ-54179060
    D.3.9.3Other descriptive nameIBRUTINIB
    D.3.9.4EV Substance CodeSUB120863
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number70
    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 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 nameIbrutinib
    D.3.2Product code JNJ-54179060
    D.3.4Pharmaceutical form Oral suspension
    D.3.4.1Specific paediatric formulation Yes
    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 INNIbrutinib
    D.3.9.1CAS number 936563-96-1
    D.3.9.2Current sponsor codeJNJ-54179060
    D.3.9.3Other descriptive nameIBRUTINIB
    D.3.9.4EV Substance CodeSUB120863
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number70
    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
    Mature B-Cell Neoplasm
    Neoplasia Cellule B Mature
    E.1.1.1Medical condition in easily understood language
    Mature B-Cell Cancer
    Tumore Cellule B Mature
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level HLGT
    E.1.2Classification code 10025320
    E.1.2Term Lymphomas non-Hodgkin's B-cell
    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
    Part 1:
    Confirm that the pharmacokinetics in pediatric subjects is consistent with that in adults

    Part 2:
    Assess efficacy (EFS) of ibrutinib in combination with RICE or RVICI background therapy compared to RICE or RVICI background therapy alone
    PARTE 1:
    - Confermare che la farmacocinetica nei soggetti pediatrici è in linea con quella negli adulti
    PARTE 2:
    - Valutare l'efficacia (sopravvivenza libera da eventi [EFS]) di ibrutinib in combinazione con la terapia di background: RICE o RVICI rispetto alla sola terapia di background: RICE o RVICI
    E.2.2Secondary objectives of the trial
    Part 1:
    -Evaluate the safety and tolerability of ibrutinib in combination with RICE or RVICI background therapy in pediatric subjects with B-cell malignancies
    -Assess anti-tumor activity of ibrutinib as add-on to RICE or RVICI regimens
    -Assess disease-specific biomarkers
    -Assess the pharmacodynamic response
    -Acceptability and palatability assessment of all ibrutinib formulations

    Part 2:
    -Evaluate the safety and tolerability of ibrutinib in combination with RICE or RVICI background therapy in pediatric subjects and young adults with B-cell malignancies
    -Determine the ORR
    -Evaluate tumor volume reduction at Day 14
    -Determine the number and proportion of subjects who proceed to stem cell transplantation
    -Evaluate the time to response
    -Measure the duration of response
    -Evaluate long-term survival (EFS at 2 and 3 years)
    -Evaluate overall survival
    -Assess disease-specific biomarkers
    For the remaining secondary objectives, please refer to protocol page 28.
    Pt 1:Valutare:sicurezza tollerabilità ibrutinib in combinazione con terapia background con RICE o RVICI in soggetti pediatrici con neoplasie maligne a cellule B; attività antitumorale di ibrutinib in aggiunta ai regimi RICE o RVICI;biomarcatori specifici della malattia;risposta farmacodinamica;accettabilità e palatabilità di tutte le formulazioni di ibrutinib.
    PT 2: Valutare: sicurezza e tollerabilità di ibrutinib in combinazione con la terapia di background con RICE o RVICI in oggetti pediatrici e giovani adulti con neoplasie maligne a cellule B;riduzione di volume del tumore al Giorno 14;lasso temporale fino alla risposta;sopravvivenza a lungo termine (EFS a 2 e 3 anni);sopravvivenza globale;biomarcatori specifici della malattia;Determinare
    tasso di risposta globale (ORR);numero e la proporzione di soggetti che procedono con il trapianto di cellule staminali;Misurare durata della risposta;Per i rimanenti obiettivi secondari si prega di far riferimento alla pagina 28 del protocollo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Participants with 1 to less than (<) 18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial diagnosis of mature B-cell non-Hodgkin lymphoma (NHL) occurred at <18 years of age (Part 2 only)
    - Participants must be in first or later recurrence or have disease that is primarily refractory to conventional therapy
    - Participants must have at least 1 of the following: 1 site of measurable disease greater than (>) 1 centimeter (cm) in the longest diameter by radiological imaging; bone marrow involvement; cerebrospinal fluid with blasts present
    - Participants with lansky-Karnofsky score of greater than or equal to (>=) 50
    - Adolescent women/young women of childbearing potential must have a negative highly sensitive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening before enrollment/randomization. Adolescent/young women who are pregnant or breastfeeding are ineligible for this study
    - Età compresa tra 1 e 18 anni (solo Parte 1) o tra 1 e 30 anni se la diagnosi iniziale di NHL a cellule B mature è avvenuta a un'età <18 anni (solo Parte 2);
    - Condizione di prima o successiva ricorrenza o di patologia prevalentemente refrattaria a terapia convenzionale;
    - Presenza di almeno uno dei fattori seguenti: sede della malattia misurabile più grande di (>) 1 cm nel diametro più lungo mediante imaging radiologico; coinvolgimento del midollo osseo; liquido cerebrospinale con presenza di blasti;
    - Punteggio Lansky-Karnofsky ≥50;
    - Le adolescenti/ragazze in età fertile devono presentare un risultato negativo a un test di gravidanza sul siero altamente sensibile o a un test di gravidanza sulle urine (beta-gonadotropina corionica umana, β-hCG) allo screening, prima di arruolamento/randomizzazione. Le adolescenti/ragazze in stato di gravidanza o che allattano al seno non sono idonee allo studio.
    E.4Principal exclusion criteria
    - Participants with ongoing anticoagulation treatment with warfarin or
    equivalent vitamin K antagonists (example phenprocoumon), or ongoing
    treatment with agents known to be strong CYP3A4/5 inhibitors, or has
    taken any disallowed therapies as noted in Section 8.2, Prohibited
    Medications, before the planned first dose of study drug
    - Participants with inherited or acquired bleeding disorders
    - Participants with clinically significant arrhythmias, complex congenital
    heart disease, or left ventricular ejection fraction (LVEF) <50 percent
    (%) or shortening fraction (SF) <=28%
    - Participants with known history of human immunodeficiency virus
    (HIV) or active Hepatitis B or C virus
    - Participants with any condition that could interfere with the absorption
    or metabolism of ibrutinib including malabsorption syndrome, disease
    significantly affecting gastrointestinal function, or resection of the
    stomach or small bowel
    - Participants with known allergies, hypersensitivity, or intolerance to
    ibrutinib or its excipients (refer to Investigator's Brochure)
    - Terapia anticoagulante in corso con warfarin o antagonisti della vitamina K equivalenti (ad es. fenprocumone) oppure terapia in corso con agenti noti per essere forti inibitori del CYP3A4/5 oppure assunzione di terapie non ammesse, come indicato nella sezione 8.2, Farmaci vietati, prima della prima dose prevista del farmaco sperimentale;
    - Problemi di sanguinamento ereditari o acquisiti;
    - Aritmie clinicamente significative, patologie cardiache congenite complesse oppure frazione di eiezione ventricolare sinistra (LVEF) < 50% o frazione di accorciamento (SF) ≤ 28%;
    - Anamnesi nota di virus dell'immunodeficienza umana (HIV) o virus dell'epatite B o C attivo;
    - Qualsiasi condizione in grado di interferire con l'assorbimento o il metabolismo di ibrutinib comprese sindrome da malassorbimento, malattia che colpisce significativamente la funzione gastrointestinale o resezione dello stomaco oppure dell'intestino tenue;
    - Note allergie, ipersensibilità o intolleranza a ibrutinib o ai suoi eccipienti (fare riferimento all’Investigator’s Brochure).
    E.5 End points
    E.5.1Primary end point(s)
    1/ Part 1: Area Under The Plasma Concentration-Time Curve (Auc) of Ibrutinib
    2/ Part 1: Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib
    3/ Part 1: Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib
    4/ Part 1: Maximum Observed Plasma Concentration (Cmax)
    5/ Part 1: Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size
    6/ Part 2: Event-free Survival [EFS]) of Ibrutinib
    1/PARTE 1: Esposizione (area sotto la curva concentrazione plasmatica-tempo [AUC]) di Ibrutinib
    2/PARTE 1: Clearance plasmatica (CL/F) (orale) apparente di Ibrutinib
    3/PARTE 1: volume di distribuzione (Vd/F) (orale) apparente di Ibrutinib
    4/PARTE 1: concentrazione plasmatica massima osservata (Cmax)
    5/PARTE 1: Relazione fra parametri di farmacocinetica ed età o corporatura
    6/PARTE 2: EFS (event free-survival) di Ibrutinib
    E.5.1.1Timepoint(s) of evaluation of this end point
    1-4 /Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3.
    5/ up to three 28-day cycles
    6/ Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (approximately 4.2 years)
    End points 1-4 : campioni raccolti prima della dose e 1, 2, 4 e 6 ore dopo la dose nel Giorno 1 e nei Giorni 7 o 8 del ciclo 1; campioni raccolti prima della dose e 1, 2, 4 e 6 ore dopo la dose nel Giorno 1 del ciclo 1 o del ciclo 3
    End point 5: fino a 3 cicli di 28 giorni di trattamento
    End point 6: dalla randomizzazione alla morte, alla progressione della malattia, o alla mancanza di CR o PR dopo 3 cicli di trattamento (circa 4,2 anni)
    E.5.2Secondary end point(s)
    1/ Part 1: Number of Participants with Adverse Events
    2/ Part 1: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR)
    3/ Part 1: Disease-specific Biomarkers Assessment
    4/ Part 1: Bruton’s tyrosine kinase (BTK) Percent Occupancy
    5/ Part 1: Visual analog Scale Score for Palatability
    6/ Part 2: Number of Participants with Adverse Events
    7/ Part 2: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR)
    8/ Part 2: Tumor Volume Reduction
    9/ Part 2: Percentage of Participants who Proceed to Stem Cell Transplantation
    10/ Part 2: Time to Response
    11/ Part 2: Duration of Response
    12/ Part 2: Percentage of Participants with Long-term Survival
    13/ Part 2: Overall Survival
    14/ Part 2: Disease-specific Biomarkers Assessment
    15/ Part 2: Bruton’s tyrosine kinase (BTK) Percent Occupancy
    16/ Part 2: Visual analog Scale Score for Palatability
    17/ Part 2: Area under the plasma concentration-time curve (AUC)
    1/PARTE 1:numero di soggetti con eventi avversi
    2/PARTE 1: Percentuale dei soggetti che ottiene una risposta completa (CR) e una risposta parziale (PR)
    3/PARTE 1: Valutazione biomarcatori specifici della malattia
    4/PARTE 1: Percentuale di occupazione di bruton tirosin chinasi (BTK)
    5/parte 1: Punteggio della scala analogica visiva per palatabilità
    6/PARTE 2: numero di partecipanti con eventi avversi
    7/PARTE 2: Percentuale dei partecipanti che ottiene una risposta completa (CR) e una risposta parziale (PR)
    8/PARTE 2: Riduzione del volume del tumore
    9/parte 2: percentuale dei soggetti che procedono con il trapianto di cellule staminali
    10/PARTE 2: tempo di risposta
    11/PARTE 2: Durata della risposta
    12/PARTE 2: percentuale dei soggetti con EFS
    13/PARTE 2: sopravvivenza globale
    14/PARTE 2: Valutazione biomarcatori specifici della malattia
    15/PARTE 2: Percentuale di occupazione di bruton tirosin chinasi (BTK)
    16/PARTE 2: Punteggio della scala analogica visiva per palatabilità
    17/PARTE 2: Area under the plasma concentration-time curve (AUC)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1/ Throughout the study duration (approx up to 4.2yrs)
    2/ Treatment Phase:D14 (Cy1),end of Cy2,EOT visit;Post treatment phase:every 12wks for first 12m,every 6m until PD/clinical cutoff for primary endpoint/or upto 2yrs after last subject enrolled,whichever occurs first
    3/ Cy1 D1, Cy2 D1, Cy3 D1&EOT visit
    4/ 4 hrs postdose on D1 and D7 or 8 of Cy1, predose on Cy2 D1 or Cy3 D1, and the EOT visit
    5/ Cy1 D1&y3 D1
    6/ Throughout the study duration (approx up to 4.2yrs)
    7/ idem timepoint nbr 2
    8/ D14
    9/ Cy2 (D28)
    10-11/ Up to 4.2yrs
    12/ 2, 3yrs
    13/ Randomization to the date of death (maximum up to 4.2yrs)
    14/ Cy1 D1, Cy2 D1, Cy3 D1 and EOT visit
    15-16/ Cy1 D1 & Cy3 D1
    17/ Predose; 1, 2, and 4 hrs postdose, either on D7 or 8 of Cy1 or on D1 of Cy2 (or Cy3)
    1:tutta la durata dello studio;2:fase di trattamento:D14 (Cy1),fine del Cy2, EOT visit; Fase di post trattamento: ogni 12 sett. nei primi 12 mesi, ogni 6 mesi fino a comparsa di PD, cut-off clinico per l'endpoint primario oppure fino a 2 anni dopo l'arruolamento dell'ultimo soggetto, a seconda dell’evento che si verifica per primo;3: C1D1, C2D1, C3D1 e EOT visit;4: 4 h dopo la dose, al D1 e al D7 o 8, prima della dose il C2D1 o C3D1,e alla visita EOT;5:C1D1 e C3D1;6:tutta la durata dello studio (ca 4,2 anni);7:idem timepoint numero 2;8:D14;9: Cy2 (D28);10 e 11:fino a 4,2yrs;12: 2, 3yrs;13:dalla randomizzazione alla data del decesso (massimo fino a 4,2yrs);14: C1D1,C2D1,C3D1 e EOT visit;15 e 16:C1D1 e C3D1;17:prima della dose;1, 2,e 4 h dopo la dose,o il D7 o 8 del C1 o il D1 del C2 o C3.
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarker analysis
    Analisi dei biomarcatori
    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 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 Yes
    E.8.2.3.1Comparator description
    chemio-immunoterapia di background
    Background Chemoimmunotherapy
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA54
    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
    Argentina
    Belgium
    Brazil
    Bulgaria
    Canada
    China
    Czech Republic
    France
    Germany
    Hungary
    Italy
    Japan
    Mexico
    Netherlands
    Poland
    Romania
    Russian Federation
    Spain
    Switzerland
    Taiwan
    Turkey
    Ukraine
    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
    The end of study is defined as when approximately 60 EFS events have occurred in Part 2 (death, disease progression, or lack of CR or PR after 3 cycles of treatment based on blinded independent event review), or the sponsor terminates the study, whichever comes first.
    La fine dello studio viene sancita quando si sono verificati all'incirca 60 eventi EFS nella Parte 2 (decesso, progressione della malattia o mancanza di CR o PR dopo 3 cicli di trattamento sulla base di un'analisi degli eventi indipendente in cieco) oppure lo sponsor termina lo studio, a seconda dell'evento che si verifica per primo.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months9
    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.1.1Number of subjects for this age range: 82
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 2
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 45
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 35
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 2
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 46
    F.4.2.2In the whole clinical trial 84
    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)
    Standard of care treatment will be the expected treatment for this condition.
    Al termine dello studio i pazienti riceveranno il trattamento standard, secondo pratica clinica, per questa condizione
    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 Decision2016-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-08
    P. End of Trial
    P.End of Trial StatusOngoing
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA