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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42316   clinical trials with a EudraCT protocol, of which   6969   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

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    Summary
    EudraCT Number:2012-000601-74
    Sponsor's Protocol Code Number:PCI-32765MCL3001
    National Competent Authority:Ireland - HPRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-08-09
    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 ConcernedIreland - HPRA
    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
    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
    A.3.2Name or abbreviated title of the trial where available
    NAP
    A.4.1Sponsor's protocol code numberPCI-32765MCL3001
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1135-6930
    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 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 29-2333CM
    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 Yes
    D.2.1.1.1Trade name IMBRUVICA®
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1115
    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 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 RoleComparator
    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
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    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 nameTemsirolimus
    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 INNTEMSIROLIMUS
    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
    E.1.1.1Medical condition in easily understood language
    Relapsed or refractory Mantle Cell Lymphoma
    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 PT
    E.1.2Classification code 10026801
    E.1.2Term Mantle cell lymphoma refractory
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    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 rituximab-containing chemotherapy regimen.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    •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.

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Confirmed diagnosis of mantle cell lymphoma (MCL)
    - 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)
    - Documented relapse or disease progression following the last anti-MCL treatment
    - At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
    - Eastern Cooperative Oncology Group performance status grade 0 or 1
    - Protocol-defined hematology and biochemical laboratory values
    E.4Principal exclusion criteria
    - Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates 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 or equivalent vitamin K antagonist
    - Requires treatment with strong CYP3A 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
    E.5 End points
    E.5.1Primary end point(s)
    Progression free survival
    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)
    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
    E.5.2.1Timepoint(s) of evaluation of this end point
    -up to 3 years after last patient randomized
    -up to 3 years after last patient randomized
    -Month 12
    -up to 3 years after last patient randomized
    -up to 3 years after last patient randomized
    -up to 30 days after last dose of study medication
    -Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
    -Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
    -Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
    -Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
    -up to 3 years after last patient randomized
    -up to 3 years after last patient 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
    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
    Biomarker analysis
    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 Yes
    E.8.2.3.1Comparator description
    Temsirolimus
    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 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
    Belgium
    Brazil
    Canada
    Colombia
    Czech Republic
    France
    Germany
    Hungary
    Ireland
    Italy
    Korea, Republic of
    Mexico
    Netherlands
    Poland
    Portugal
    Russian Federation
    Spain
    Sweden
    Taiwan
    Ukraine
    United Kingdom
    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.
    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 months0
    E.8.9.1In the Member State concerned days26
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days26
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 84
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 196
    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 state4
    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.
    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 Decision2012-10-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-09-04
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-12-15
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