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    Summary
    EudraCT Number:2014-002272-88
    Sponsor's Protocol Code Number:54767414MMY3007
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-05-12
    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 ConcernedGreece - EOF
    A.2EudraCT number2014-002272-88
    A.3Full title of the trial
    A Phase 3, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib)
    Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination with VMP
    (D-VMP), in Subjects with Previously Untreated Multiple Myeloma who are Ineligible for
    High-dose Therapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Combination of Daratumumanb and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants with Previously Untreated Multiple Myeloma
    A.4.1Sponsor's protocol code number54767414MMY3007
    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 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 N.V.
    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+31 715242166
    B.5.5Fax number+31 715242110
    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 DARZALEX
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International N.V.
    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/3/13/1153
    D.3 Description of the IMP
    D.3.1Product nameDaratumumab
    D.3.2Product code HuMax-CD38
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARATUMUMAB
    D.3.9.1CAS number 945721-28-8
    D.3.9.2Current sponsor codeJNJ-54767414 (Daratumumab)
    D.3.9.3Other descriptive nameHUMAX-CD38
    D.3.9.4EV Substance CodeSUB175772
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typehuman monoclonal antibody
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1153
    D.3 Description of the IMP
    D.3.1Product nameDaratumumab co-formulated with recombinant human hyaluronidase (rHuPH20)
    D.3.2Product code JNJ-54767414
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARATUMUMAB
    D.3.9.1CAS number 945721-28-8
    D.3.9.2Current sponsor codeJNJ-54767414
    D.3.9.3Other descriptive nameHuMax-CD38, 3003-005
    D.3.9.4EV Substance CodeSUB175772
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Multiple myeloma
    E.1.1.1Medical condition in easily understood language
    Multiple myeloma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    E.1.2System Organ Class 100000004864
    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 is to determine if the addition of daratumumab to VMP will prolong PFS compared with VMP.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
     To determine if the addition of daratumumab to VMP will improve clinical outcome as measured by:
     Time to disease progression (TTP)
     CR rate
     Minimal residual disease (MRD) negativity rate
     PFS2 (defined as time from randomization to progression on the next line of therapy or death, whichever comes first)
     Time to next treatment
     Overall response rate (partial response [PR] or better)
     Stringent CR (sCR) rate
     Very good partial response (VGPR) or better rate
     Time to response
     Duration of response
     Overall survival
    To assess patient reported outcomes and heath economic/resource utilization
     To determine the pharmacokinetics and immunogenicity of daratumumab in all subjects and the immunogenicity of recombinant human hyaluronidase PH20 (rHuPH20) in subjects receiving daratumumab SC
     To assess the safety and tolerability of daratumumab when administered in combination with VMP
    Please see protocol for a full list of objectives.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by
    the central laboratory, and defined in protocol .
    - Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in participants <65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation
    - Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
    - Meet the clinical laboratory criteria as specified in the protocol
    - A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
    - Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner’s vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy

    Please see the protocol for a complete list of the inclusion criteria.
    E.4Principal exclusion criteria
    - Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma - Participant has a diagnosis of Waldenstrom’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with
    lytic bone lesions - Participant has prior or current systemic therapy or stem cell transplantation (SCT) for multiple myeloma, with the exception of an emergency use of a short course of corticosteroids before treatment
    - Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4
    - Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
    - Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study

    Please see the protocol for a complete list of the exclusion criteria.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is PFS, which is defined as the duration from the date of randomization to
    either progressive disease or death, whichever comes first. Disease progression will be determined according to the IMWG criteria. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. Relapse from CR by positive immunofixation or trace amount of M-protein is not considered to be progressive disease and is not included in the PFS calculation.
    As the superiority of daratumumab combined with VMP over VMP alone with respect to PFS was established at the second interim analysis, the interim PFS analysis will serve as the primary PFS analysis, which otherwise was to occur when approximately 360 PFS events had been observed.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assess at approximately 41 months from randomization
    E.5.2Secondary end point(s)
    - Time to disease progression (TTP) is defined as the time from the date of randomization to the date of first documented evidence of PD, as defined in the IMWG criteria. For subjects who have not progressed, data will be censored at the date of the disease evaluation before the start of any subsequent anti-myeloma therapy.
    - CR rate, defined as the percentage of subjects achieving CR, as defined by:
    - Negative immunofixation of serum and urine, and
    - Disappearance of any soft tissue plasmacytomas, and
    - <5% PCs in bone marrow
    - For those subjects with negative or low SPEP (≤0.2 g/L) and suspected daratumumab interference on immunofixation, a reflex assay using anti-idiotype antibody will be utilized to confirm daratumumab interference and rule out false positive immunofixation. Subjects who have confirmed daratumumab interference, but meet all other clinical criteria for CR or sCR, will be considered CR/sCR.
    - MRD negativity rate, defined as the proportion of subjects who have negative MRD at any time point after the date of randomization.
    - Progression-free Survival on Next line of Therapy (PFS2), defined as the time from randomization to progression on the next line of treatment or death, whichever comes first. Disease progression will be based on investigator judgment. Subjects who are still alive and not yet progressed on the next line of treatment will be censored on the last date of follow-up.
    - Time to next treatment, defined as the time from randomization to the start of the next-line treatment.
    - Overall response rate (ORR), defined as the proportion of subjects who achieve PR or better, according to the IMWG criteria, during or after the study treatment.
    - sCR rate, defined as the percentage of subjects achieving CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
    - Proportion of subjects who achieve VGPR or better, defined as the proportion of subjects achieving VGPR and CR (including sCR) according to the IMWG criteria during or after the study treatment at the time of data cutoff.
    - Time to response, defined as the time between randomization and the first efficacy evaluation that the subject has met all criteria for PR or better. For subjects without response, data will be censored either at the date of progressive disease or, in the absence of progressive disease, at the last disease evaluation before the start of subsequent antimyeloma therapy.
    - Duration of response, calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria. For subjects who have not progressed, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy.
    - OS, measured from the date of randomization to the date of the subject’s death. If the subject is alive or the vital status is unknown, then the subject’s data will be censored at the date the subject was last known to be alive.
    - Impact of D-VMP compared to VMP on patient-reported perception of global health.
    - Clinical efficacy of D-VMP in high risk molecular subgroups compared to VMP alone.
    - Summary of subject’s preference of route of treatment administration.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - For secondary end points 1-4, 6-9 = Assess at approximately 41 months
    from randomization
    - For secondary end points 5 = Week 58, 84, and 110
    - For secondary end points 10 = Assess at approximately 41 months after first patient randomized up to a maximum of 5 years after last participant is dosed
    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 Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA129
    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
    Australia
    Brazil
    Canada
    Japan
    United States
    Poland
    Bulgaria
    Romania
    Spain
    Czechia
    Germany
    Greece
    Italy
    Belgium
    Croatia
    Georgia
    Hungary
    North Macedonia
    Portugal
    Russian Federation
    Turkey
    Ukraine
    United Kingdom
    Serbia
    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 one of the following occurs:
    - when all subjects who are still receiving study treatment after the final OS analysis have access through another source such as a commercial availability, continued access through a dedicated long-term extension study, or a patient access program,
    - when all subjects have discontinued daratumumab treatment,
    - if the first 2 are not met, then by July 2024, whichever occurs first.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years8
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years8
    E.8.9.2In all countries concerned by the trial months5
    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.1.1.1In 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: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 640
    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 state47
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 503
    F.4.2.2In the whole clinical trial 700
    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)
    If you are benefiting from study treatment when the study is over, the option to continue study medication treatment will be made available to you; your study doctor will explain the requirements for continued use of study medication.
    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 Decision2015-05-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-30
    P. End of Trial
    P.End of Trial StatusOngoing
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    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.

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