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    Summary
    EudraCT Number:2012-000601-74
    Sponsor's Protocol Code Number:PCI-32765MCL3001
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-12-11
    Trial results View 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 number2012-000601-74
    A.3Full title of the trial
    A Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects with Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy
    Uno studio di fase 3, randomizzato, controllato, in aperto dell'inibitore della tirosin-chinasi di Bruton (Btk), Ibrutinib, verso Temsirolimus in soggetti affetti da linfoma mantellare (MCL) recidivo o refrattario che hanno ricevuto almeno una precedente terapia.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy
    Uno studio su Ibrutinib (inibitore della tirosin-chinasi di Bruton) verso Temsirolimus in soggetti affetti da linfoma mantellare (MCL) recidivo o refrattario che hanno ricevuto almeno una precedente terapia.
    A.4.1Sponsor's protocol code numberPCI-32765MCL3001
    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 SponsorJANSSEN-CILAG INTERNATIONAL N.V.
    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 CILAG SPA
    B.4.2CountryItaly
    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 code2333CM
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31 (0)71 524 21 66
    B.5.5Fax number+31 (0)71 524 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 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
    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.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    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 Yes
    D.2.1.1.1Trade name TORISEL*EV 1FL 30MG+1FL 1,8ML
    D.2.1.1.2Name of the Marketing Authorisation holderPFIZER ITALIA Srl
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 162635-04-3
    D.3.9.4EV Substance CodeSUB21308
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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
    Relapsed or refractory Mantle Cell Lymphoma
    Linfoma mantellare recidivo o refrattario
    E.1.1.1Medical condition in easily understood language
    Relapsed or refractory Mantle Cell Lymphoma
    Linfoma mantellare recidivo o refrattario
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10026808
    E.1.2Term Mantle zone lymphoma refractory
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10026807
    E.1.2Term Mantle zone lymphoma recurrent
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10026806
    E.1.2Term Mantle zone lymphoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate whether treatment with ibrutinib compared with temsirolimus will result in prolongation of PFS, as determined by blinded independent central review, in subjects with relapsed or refractory MCL who have received at least 1 prior rituximabcontaining chemotherapy regimen.
    L'obiettivo primario dello studio è valutare se il trattamento con ibrutinib, confrontato con temsirolimus, risulterà in un prolungamento della sopravvivenza libera da progressione (PFS) in soggetti affetti da linfoma mantellare (MCL) recidivo o refrattario, che hanno ricevuto almeno 1 precedente regime chemioterapico contenente rituximab.
    E.2.2Secondary objectives of the trial
    •To evaluate the overall response rate (CR + PR) •To evaluate overall survival •To evaluate the 1-year survival rate •To evaluate duration of response •To evaluate time-to-next treatment (TTNT) •To evaluate the safety of ibrutinib and temsirolimus •To characterize the pharmacokinetics of ibrutinib •To evaluate patient-reported outcomes (PRO) utilizing the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and EuroQol (EQ- 5D) •To evaluate medical resource utilization (MRU) information •To identify biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways and to explore their association with response to ibrutinib •To explore the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information.
    -Valutare la percentuale di risposta generale (CR+PR) -Valutare la sopravvivenza generale -Valutare la percentuale di sopravvivenza a 1 anno -Valutare la durata della risposta -Valutare il tempo al trattamento successivo -Valutare la sicurezza di Ibrutini e Temsirolimus -Caratterizzare la farmacocinetica di Ibrutinib -Valutare gli esiti riportati dai pazienti sulla base dei quationari FACT-Lym e EQ5D -Valutare informazioni di utilizzo delle risorse mediche -Identificare biomarcatori che alterano il segnale dei recettori Bcell o attivano vie alternative di segnale e esplorare la loro associazione alla risposta a Ibrutinib -Esplorare la potenziale relazione tra le metriche di esposizione a Ibrutinib e informazioni cliniche significative e biomarcatori
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. 18 years of age or older. 2. Diagnosis of MCL reviewed and approved by central pathology laboratory prior to randomization − diagnosis report from local laboratory must include morphology and expression of either cyclin D1 in association with one B-cell marker (eg, CD19, CD20, or PAX5) and CD5 or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR) − if report from local laboratory is not available, diagnosis must be confirmed by central pathology laboratory based on the criteria above 3. Received at least 1 prior rituximab-containing chemotherapy regimen. Separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a > 6 month treatment-free interval. 4. Documented relapse or disease progression following the last anti-MCL treatment. 5. At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions. 6. Eastern Cooperative Oncology Group performance status grade 0 or 1 7. Hematology values must be within the following limits within 7 days prior to randomization: a. Absolute neutrophil count (ANC) ≥ 1000/mm3 independent of growth factor support. b. Platelets ≥ 75,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement independent of transfusion support. c. Hemoglobin level ≥ 8 g/dL independent of transfusion support. 8. Biochemical values within the following limits within 7 days prior to randomization: a.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) b.Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin. c. Serum creatinine ≤ 2 x ULN JNJ 54179060 d. Fasting serum cholesterol level ≤ 350 mg/dL e. Fasting serum triglyceride level ≤ 400 mg/dL 9. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study (3 months for both men and women) consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during the study and for 3 months after receiving the last dose of study drug. 10.Women of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at Screening. 11. Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
    1. Età ≥ 18 anni. 2. Diagnosi di MCL rivista e approvata dal laboratorio centrale di patologia prima della randomizzazione − il referto diagnostico del laboratorio locale deve includere la morfologia e l’espressione della ciclina D1 in associazione ad un marcatore delle cellule B (ad es. CD19, CD20, o PAX5) e CD5 oppure evidenza della traslocazione genica t(11;14) sulla base dell’esame di citogenetica, l'ibridazione fluorescente in situ (FISH), oppure reazione a catena della polimerasi (PCR) − se il referto del laboratorio locale non è disponibile, la diagnosi deve essere confermata dal laboratorio centrale di patologia sulla base dei criteri di cui sopra 3. Aver ricevuto almeno 1 precedente regime di chemioterapia contenente rituximab. Le linee terapeutiche separate sono definite come terapie singole o di associazione intervallate dalla progressione della malattia o da un periodo senza trattamento &gt; 6 mesi. 4. Documentata recidiva o progressione della malattia successivamente all'ultimo trattamento anti-MCL. 5. Almeno 1 sede misurabile di malattia in base ai Revised Response Criteria for Malignant Lymphoma. La sede della malattia deve essere di almeno 1,5 cm sull'asse maggiore senza tener conto di quello minore, oppure di almeno 1 cm su quello minore senza tener conto dell'asse maggiore, e deve essere chiaramente misurabile lungo due dimensioni perpendicolari. 6. Punteggio di ECOG (Eastern Cooperative Oncology Group) di 0 o 1 7. I valori ematologici devono essere entro i seguenti limiti nei 7 giorni precedenti la randomizzazione: a. Conta assoluta dei neutrofili (ANC) ≥ 1000 /mm3 indipendente dal supporto dei fattori di crescita. b. Piastrine ≥ 75.000/mm3 o ≥ 50.000/mm3 nel caso in cui si abbia coinvolgimento del midollo osseo indipendente dal supporto di trasfusioni. c. Livello di emoglobina ≥ 8 g/dl indipendente dal supporto di trasfusioni. 8. I valori biochimici devono essere entro i seguenti limiti nei 7 giorni precedenti la randomizzazione: a. Alanina aminotransferasi (ALT) e aspartato aminotransferasi (AST) ≤ 3 volte il limite superiore alla norma (ULN). b.Bilirubina totale ≤ 1,5 x ULN a meno che l'aumento di bilirubina non sia dovuta alla sindrome di Gilbert o sia di origine non- epatica. c. Creatinina sierica ≤ 2 x ULN. d. Livello del colesterolo sierico a digiuno ≤ 350 mg/dl . e. Livello sierico dei trigliceridi a digiuno ≤ 400 mg/dl . 9. Le donne in età fertile e gli uomini sessualmente attivi devono adottare misure contraccettive altamente efficaci durante e dopo lo studio (3 mesi sia per gli uomini che per le donne) e coerenti con le regolamentazioni locali sull'impiego di metodi contraccettivi per i soggetti partecipanti a sperimentazioni cliniche. Gli uomini non dovranno donare lo sperma durante lo studio e nei 3 mesi successivi all’assunzione dell’ultima dose del farmaco dello studio. 10. Le donne in età fertile devono presentare un test di gravidanza sul siero (gonadotropina corionica ß umana [ß-HCG]) o sulle urine negativo allo screening. 11. I soggetti (o i relativi rappresentanti legali autorizzati) devono firmare un modulo di consenso informato che indica che hanno compreso lo scopo dello studio e le relative procedure e che intendono prendervi parte.
    E.4Principal exclusion criteria
    - Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxinimmunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of randomization - Prior treatment with temsirolimus, other mTOR inhibitors, ibrutinib, or other Bruton's tyrosine kinase (BTK) inhibitors - Known central nervous system lymphoma - Received an allogeneic or autologous hematopoietic stem cell transplant <=6 months from the date of randomization and on immunosuppressive therapy or have evidence of active graft versus host disease - Diagnosed or treated for malignancy other than MCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease - History of stroke or intracranial hemorrhage within 6 months prior to randomization - Requires anticoagulation with warfarin - Requires treatment with strong CYP3A4/5 or CYP2D6 inhibitors - Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification - Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection or any uncontrolled active systemic infection requiring intravenous antibiotics - Woman who is pregnant or breast-feeding - Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
    1. È stato sottoposto a: trattamento con nitrosuree nelle 6 settimane precedenti, chemioterapia nelle 3 settimane precedenti, anticorpi anticancro terapeutici nelle 4 settimane precedenti, radioimmunoconiugati o immunotossine nelle 10 settimane precedenti, radioterapia o altri farmaci sperimentali nelle 3 settimane precedenti o ad un intervento chirurgico maggiore nelle 4 settimane precedenti la randomizzazione. 2. Precedente trattamento con temsirolimus, altri inibitori di mTOR, ibrutinib, o altri inibitori di BTK. 3. Presenza di linfoma del sistema nervoso centrale (CNS) . 4. Ha ricevuto un trapianto allogeneico o autologo di cellule staminali emopoietiche nei 6 mesi precedenti la data di randomizzazione e si trova in terapia immunosoppressiva oppure presenta evidenza di malattia del trapianto contro l'ospite. 5. Presenta diagnosi o è in terapia per tumore maligno diverso da MCL, fatta eccezione per: a. Tumore maligno trattato con intento curativo e nessuna malattia attiva presente per un periodo ≥ 3 anni prima della randomizzazione . b. Cancro della pelle diverso dal melanoma adeguatamente trattato o lentigo maligna senza segnali di progressione della malattia. c. Carcinoma della cervice in situ adeguatamente trattato senza evidenza di malattia. 6. Storia di ictus o emorragia intracranica nei 6 mesi precedenti alla randomizzazione. 7. Necessita di anticoagulazione con warfarin. 8. Necessita di trattamento con forti inibitori del CYP3A4/5 o del CYP2D6. 9. Presenta una malattia cardiovascolare clinicamente significativa come aritmie sintomatiche o non controllate, insufficienza cardiaca congestizia o infarto del miocardio nei 6 mesi precedenti lo screening o altra malattia cardiaca di classe 3 (moderata) o classe 4 (grave) come definita dalla New York Heart Association Functional Classification. 10. Nota storia di infezione da virus dell'immunodeficienza umana (HIV) o da virus dell'epatite C (HCV) attiva o da virus dell'epatite B (HBV) attiva o di qualsiasi infezione sistemica attiva non controllata che richieda antibiotici per via endovenosa (IV). 11. È una donna incinta o che allatta. 12. Qualsiasi malattia potenzialmente mortale, condizioni mediche o disfunzioni d’ organo che, secondo lo sperimentatore, potrebbero compromettere la sicurezza del soggetto, interferire con l'assorbimento o il metabolismo delle capsule di ibrutinib o che potrebbero mettere a rischio i risultati dello studio.
    E.5 End points
    E.5.1Primary end point(s)
    Progression free survival
    Sopravvivenza libera da progressione di malattia
    E.5.1.1Timepoint(s) of evaluation of this end point
    clinical cutoff (defined by 178 patients with progression free survival events; up to 3 years after the last patient is randomized)
    cut off clinico (definito come 178 di sopravvivenza libera da progressione di malattia; fino a 3 anni dopo l'ultimo paziente randomizzato)
    E.5.2Secondary end point(s)
    - Overall response rate - Overall survival - 1-year survival rate - Duration of response - Time-to-next treatment - Number of participants with adverse events - Mean plasma concentrations of ibrutinib - Maximum observed plasma concentration of ibrutinib - Minimum observed plasma concentration of ibrutinib - Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib - Mean change from baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale score - Mean change from baseline in EuroQol (EQ-5D-5L) index score - Mean change from baseline in medical resource utilization - Mean change from baseline in biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways - Mean change from baseline in identified resistance biomarkers from bone marrow
    - Percentuale di risposta generale - Sopravvivenza generale - Percentuale di sopravvivenza a 1 anno - Durata della risposta - Tempo al trattamento successivo - Numero di soggetti con eventi avversi - Concentrazione plasmatica media di Ibrutinib - Massima concentrazione plasmatica osservata di Ibrutinib - Area sotto la curva concetrazione plasmatica/tempo da 0 a 24 ore di Ibrutinib - Variazione media rispetto al basale nel punteggio del FACT-Lym - Variazione media rispetto al basale del punteggio EQ5D - Variazione media rispetto al basale nell'utilizzo delle risorse mediche - Variazione media rispetto al basale dei biomarcatori che alterano il segnale dei recettori Bcell o attivano vie alternative di segnale - Variazione media rispetto al basale dei biomarcatori identificati dal midollo
    E.5.2.1Timepoint(s) of evaluation of this end point
    -up to 3 years after the last pt is randomized - up to 3 years after the last pt is randomized - Month 12 - up to 3 years after the last pt is randomized - up to 3 years after the last pt is randomized - up to 30 days after the last dose of study medication - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - up to 3 years after the last pt is randomized - up to 3 years after the last pt is randomized - up to 30 days from last dose of study medication - up to 30 days from last dose of study medication - up to 30 days from last dose of study medication
    Fino 3 anni dopo la randomizzazione dell'ultimo soggetto - Fino a 3 anni dopo la randomizzazione dell'ultimo soggetto - 12 mesi - Fino a 3 anni dopo la randomizzazione dell'ultimo soggetto - Fino a 3 anni dopo la randomizzazione dell'ultimo soggetto - fino a 30 giorni dopo l'ultima dose - Cicli 1-3: predose al giorno 1; 1,2,4 ore dopo la dose - Cicli 1-3: predose al giorno 1; 1,2,4 ore dopo la dose - Cicli 1-3: predose al giorno 1; 1,2,4 ore dopo la dose - Cicli 1-3: predose al giorno 1; 1,2,4 ore dopo la dose - Fino a 3 anni dopo la randomizzazione dell'ultimo soggetto - Fino a 3 anni dopo la randomizzazione dell'ultimo soggetto -fino a 30 giorni dopo ultima dose di farmaco dello studio - fino 30 gg dopo ultima dose - fino 30 gg dopo l'ultima dose - fino 30 gg dopo ultima dos
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic 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
    biomarkers analysis
    analisi 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 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) Yes
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA77
    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
    Brazil
    Canada
    Chile
    Colombia
    Korea, Democratic People's Republic of
    Mexico
    Russian Federation
    Taiwan
    Thailand
    Ukraine
    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
    Study end is considered to be completed when 80% of the randomized subjects have died, or 3 years after the last subject is randomized, or the Sponsor terminates the study, whichever comes first.
    Lo studio termina all'accadere di uno dei seguenti eventi: -80% di decessi dei pazienti randomizzati -3 anni dopo l'ultima randomizzazione -studio interrotto dallo sponsor
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months48
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months51
    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.1.1Number of subjects for this age range: 0
    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: 4
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 8
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 172
    F.4.2.2In the whole clinical trial 280
    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)
    The sponsor will ensure that subjects benefiting from treatment with ibrutinib or temsirolimus will be able to continue treatment after the end of the study.
    Lo sponsor garantisce ai pazienti che beneficiano dell'assunzione di Ibrutinib o Temsirolimus la continuazione del trattamento dopo la fine dello studio
    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 Decision2013-03-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-11-19
    P. End of Trial
    P.End of Trial StatusCompleted
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