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    Summary
    EudraCT Number:2015-002509-13
    Sponsor's Protocol Code Number:MK3475-183
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-02-08
    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 number2015-002509-13
    A.3Full title of the trial
    A phase III study of Pomalidomide and low dose Dexamethasone with or without Pembrolizumab (MK3475) in refractory or relapsed and refractory Multiple Myeloma (rrMM) (KEYNOTE 183)
    Studio di fase III su pomalidomide e desametasone a basso dosaggio con o senza pembrolizumab (MK3475) nel mieloma multiplo refrattario oppure recidivante e refrattario (rrMM) (KEYNOTE 183)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase III study of Pomalidomide and Dexamethasone with or without Pembrolizumab in refractory or relapsed and refractory Multiple Myeloma (rrMM).
    Studio di fase III su pomalidomide e desametasone con o senza pembrolizumab nel mieloma multiplo refrattario oppure recidivante e refrattario (rrMM).
    A.3.2Name or abbreviated title of the trial where available
    A phase III study of Pomalidomide and Dexamethasone with or without Pembrolizumab in rrMM
    Studio di fase III su pomalidomide e desametasone con o senza pembrolizumab in rrMM.
    A.4.1Sponsor's protocol code numberMK3475-183
    A.5.4Other Identifiers
    Name:IND No:Number:118604
    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 SponsorMERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
    B.1.3.4CountryUnited States
    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 supportMerck Sharp&Dohme Corp sussidiaria di Merck&Co Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMSD Italia Srl
    B.5.2Functional name of contact pointDivisione Ricerca Clinica
    B.5.3 Address:
    B.5.3.1Street AddressVia Fratelli Cervi, snc - Centro Direzionale Milano Due - Palazzo Canova
    B.5.3.2Town/ citySegrate (MI)
    B.5.3.3Post code20090
    B.5.3.4CountryItaly
    B.5.4Telephone number+39 02 21018402
    B.5.5Fax number+39 02 21018629
    B.5.6E-mailgcto.italy@merck.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 namePembrolizumab
    D.3.2Product code MK-3475
    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 INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.3Other descriptive nameAnticorpo monoclonale anti-PD-1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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) Yes
    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.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 Imnovid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Ltd
    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 nameImnovid
    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 INNPomalidomide
    D.3.9.1CAS number 19171-19-8
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive namePomalidomide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 Imnovid
    D.2.1.1.2Name of the Marketing Authorisation holderCelgene Europe Ltd
    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 nameImnovid
    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 INNPomalidomide
    D.3.9.1CAS number 19171-19-8
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive namePomalidomide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 4
    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 Dexamethasone 4mg Jenapharm
    D.2.1.1.2Name of the Marketing Authorisation holdermibe GmbH Arzneimittel
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameDesametasone 4mg Jenapharm
    D.3.4Pharmaceutical form Tablet
    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 INNDesametasone
    D.3.9.1CAS number 50-02-2
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive nameDesametasone
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    Patients with refractory or relapsed and refractory multiple myeloma (rrMM) who have failed at least 2 lines of prior treatment and have been previously exposed to an immunomodulatory drug (IMiDs) as lenalidomide or thalidomide and a proteasome inhibitor as bortezomib or carfilzomib.
    Pazienti con mieloma multiplo refrattario oppure recidivante e refrattario (rrMM) che hanno fallito almeno 2 precedenti linee di trattamento e sono stati precedentemente esposti ad un farmaco immunomodulatore come lenalidomide o talidomide ed a un inibitore del proteasoma come bortezomib o carfilzomib.
    E.1.1.1Medical condition in easily understood language
    Patients with multiple myeloma that has progressed after receaving at least 2 lines of prior treatment. These treatments must have included lenalidomide or thalidomide and a proteasome inhibitor.
    Pazienti con mieloma multiplo progredito dopo almeno 2 precedenti linee di trattamento. Questi trattamenti devono includere lenalidomide o talidomide e un inibitore del proteasoma.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    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 No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Compare the Progression Free Survival (PFS) as assessed by CAC blinded central review according to the International Myeloma Working Group response criteria, (IMWG criteria) between treatment arms.
    Confrontare la sopravvivenza libera da progressione (PFS) come valutata dall’analisi centrale in cieco del CAC secondo i criteri di risposta del International Myeloma Working Group (criteri IMWG) fra i due bracci di trattamento.
    E.2.2Secondary objectives of the trial
    1. Compare the Overall Survival (OS).
    2. Evaluate Overall Response Rate (ORR) and Disease Control Rate (DCR) as assessed by CAC blinded central review and as per investigator assessment using IMWG criteria or EBMT criteria for minor response only and Duration of Response (DOR) as assessed by CAC blinded central review and as per investigator assessment using IMWG criteria.
    3. Compare the Progression Free Survival (PFS) as assessed by the investigator using IMWG criteria between treatment arms.
    4.To evaluate the safety and tolerability in both treatment arms.
    1. confrontare la sopravvivenza complessiva (Overall Survival, OS).
    2. Valutare il tasso di risposta complessiva (objective response rate, ORR) e il tasso di controllo della malattia (disease control rate, DCR) secondo la valutazione dell’analisi centrale in cieco del CAC, seguendo i criteri dell’IMWG o del European Group for Blood and Bone Marrow Transplant (EBMT) per la risposta minore e la durata della risposta (duration of response, DOR) secondo la valutazione dell’analisi centrale in cieco del CAC seguendo i criteri dell’IMWG.
    3. Valutare la sicurezza e la tollerabilità in entrambi i bracci di trattamento.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described
    elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The
    objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding
    of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
    Merck condurrà una Ricerca Biomedica Futura
    su campioni di DNA (estratti dal sangue) raccolti nel corso di questo studio clinico. Tale ricerca ha lo scopo di esaminare vari biomarcatori per rispondere a domande che stanno emergendo e che non sono descritte in altre parti del protocollo (nell ambito
    dello studio principale), e verrà condotta solo su campioni di soggetti che abbiano rilasciato apposito consenso. L'obiettivo della raccolta dei campioni per la Ricerca Biomedica Futura è quello di esplorare e identificare biomarcatori che contribuiscano
    scientificamente alla comprensione delle malattie e/o delle relative terapie. L'obiettivo ultimo è quello di utilizzare tali informazioni per sviluppare farmaci più sicuri e più efficaci, e/o per garantire che i soggetti ricevano la dose giusta del giusto farmaco al momento giusto.
    E.3Principal inclusion criteria
    1. Must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy and must have failed their last line of treatment defined as documented disease progression during or within 60 days of completing their last anti-myeloma therapy (refractory to last line of treatment).
    2. Prior anti-myeloma treatments must have included an IMiD (lenalidomide or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination and subject must have failed therapy with an IMiD OR proteasome inhibitor defined as one of the following:
    • Refractory: Documented progressive disease on or within 60 days of completing treatment with an IMiD and/or proteasome inhibitor OR
    • Relapsed and refractory: In case of prior response [≥ partial response (PR)] to an IMiD or proteasome inhibitor, subjects must have relapsed within 6 months after stopping treatment with and IMiD and/or proteasome inhibitor containing regimens
    3. Confirmed diagnosis of active MM and measurable disease defined as:
    • Serum monoclonal protein (M-protein) levels ≥ 0.5 g/dL or
    • Urine monoclonal protein (M-protein) levels ≥200 mg/24-hours or
    • Subjects without measurable serum and urine M-protein levels, an abnormal serum free light chain ratio (FLC κ/λ) with involved FLC level ≥100 mg/L. (Normal serum FLC κ/λ value: 0.26 - 1.65)
    • Presence of CRAB features
    4. Provide, archival (≤60 days) or newly obtained bone marrow biopsy or aspirate material for disease assessment and biomarker analysis.
    5. Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
    1. Essere stato sottoposto in precedenza a ≥ 2 linee di trattamento di terapia anti-mieloma con fallimento dell’ultima linea di trattamento come definito da progressione documentata della malattia durante o entro 60 giorni dal completamento dell’ultima terapia anti-mieloma (refrattario all’ultima linea di trattamento).
    2. I trattamenti anti-mieloma precedenti devono aver incluso un IMiD (lenalidomide o talidomide) E un inibitore del proteasoma (bortezomib o carfilzomib) da soli o in associazione e il soggetto non deve aver risposto alla terapia con un IMiD OPPURE un inibitore del proteasoma secondo una delle definizioni seguenti:
    • Refrattario: malattia progressiva documentata a/entro 60 giorni dal completamento del trattamento con IMiD e/o inibitore del proteasoma
    OPPURE
    • Recidivante e refrattario: in caso di risposta precedente [≥ risposta parziale (RP)] a un IMiD o a un inibitore del proteasoma, i soggetti devono aver avuto una recidiva entro i 6 mesi successivi all’interruzione del trattamento con regimi contenenti un IMiD e/o un inibitore del proteasoma.
    3. Avere una diagnosi confermata di mieloma multiplo attivo e malattia misurabile definita come segue:
    • Livelli sierici di proteina monoclonale (M proteina) ≥ 0,5 g/dl o
    • Livelli di proteina monoclonale (M proteina) nelle urine ≥ 200 mg/24 ore o
    • Per i soggetti in cui i livelli di proteina M nel siero e nelle urine non siano misurabili, un tasso anormale del rapporto fra le catene libere leggere nel siero (Free light chains, FLC κ/λ) con livello della FLC coinvolta ≥ 100 mg/l. (Valore diFLC κ/λ nel siero normale: 0,26 - 1,65).
    • Presenza di caratteristiche CRAB
    4. Essere in grado di fornire biopsie di midollo osseo o materiale aspirato d’archivio (≤ 60 giorni) o prelevati ex novo per la valutazione della malattia e l’analisi dei biomarcatori allo screening.
    5. Avere un Performance Status di 0 o 1 sulla scala ECOG (Eastern Cooperative Oncology Group) Performance Scale.
    E.4Principal exclusion criteria
    1. Subjects with non-secretory or oligo-secretory myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia.
    2. History of repeated infections, primary amyloidosis, hyperviscosity or POEMS syndrome.
    3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
    4. Has had prior anti-myeloma therapy including but not limited to dexamethasone, IMiDs, proteasome inhibitors, chemotherapy, or radiation therapy within 2 weeks prior to Study Day 1 who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
    5. Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease (GVHD).
    6. Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first infusion or are planning for or are eligible for auto-SCT.
    7. Has known hypersensitivity to thalidomide, lenalidomide or dexamethasone.
    8. Has received previous therapy with pomalidomide.
    9. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
    10. Subjects with peripheral neuropathy ≥ Grade 2.
    11. Has evidence of active, non-infectious pneumonitis.
    12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
    1. Soggetti affetti da mieloma non secretorio o oligo-secretorio, mieloma multiplo asintomatico (smoldering multiple myeloma, SMM), gammopatia monoclonale di significato incerto (monoclonal gammopathy of undetermined significance, MGUS), leucemia delle cellule plasmatiche or macroglobulinemia di Waldenström.
    2. Anamnesi di ripetute infezioni, amiloidosi primaria, iperviscosità o sindrome POEMS (discrasia delle cellule plasmatiche con polineuropatia, organomegalia, endocrinopatia, proteina monoclonale e alterazioni cutanee).
    3. Ha già assunto un anticorpo monoclonale nelle 4 settimane precedenti il Giorno 1 dello studio o non si è ripreso (ossia ≤ Grado 1 o al basale) da eventi avversi dovuti agli agenti somministrati più di 4 settimane prima
    4. Si è già sottoposto a terapia anti-mieloma compresi, ma non limitati a, desametasone, IMiD, inibitori del proteasoma, chemioterapia o radioterapia nelle 2 settimane precedenti il Giorno 1 dello studio o non ha avuto una ripresa (ossia ≤ Grado 1 o al basale) da eventi avversi dovuti ad un trattamento somministrato in precedenza.
    5. È stato sottoposto a un trapianto precedente allogenico di cellule staminali ematopoietiche negli ultimi 5 anni. (I soggetti che hanno subito un trapianto da oltre i 5 anni sono idonei a condizione che non presentino sintomi di malattia del trapianto contro l’ospite (Graft versus Host Disease, GVHD).
    6. Ha ricevuto un trapianto autologo di cellule staminali (auto-SCT) entro le 12 settimane precedenti la prima infusione oppure pianifica o è idoneo all’auto-SCT.
    7. Presenta ipersensibilità nota al talidomide, al lenalidomide o al desametasone.
    8. Ha ricevuto un trattamento precedente con pomalidomide.
    9. Soggetti non in grado o non disposti a sottoporsi a profilassi tromboembolitica.
    10. Soggetti con neuropatia periferica ≥ Grado 2.
    11. Presenta evidenza di polmonite non infettiva attiva.
    12.Ha ricevuto precedentemente una terapia con un farmaco anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 o un anticorpo anti-antigene 4 dei linfociti T citotossici (Cytotoxic T-lymphocyte-associated antigen-4, CTLA4).
    E.5 End points
    E.5.1Primary end point(s)
    The primary end point of the study is Progression-free survival (PFS) – the International Myeloma Working Group response criteria (IMWG 2006) by blinded central review. PFS is defined as the time from randomization to the first documented
    disease progression per IMWG 2006 based on blinded central review or death due to any cause, whichever occurs first.
    L’obiettivo primario di questo studio è confrontare la sopravvivenza libera da progressione (PFS) valutata dall’analisi centrale in cieco del CAC, secondo i criteri dell’IMWG fra i due bracci di trattamento.
    IL PSF è definito come il tempo che intercorre tra la randomizzazione e la prima progressione di malattia documentata secondo i criteri IMWG 2006 (valutata centralmente in cieco) o la morte per qualsiasi causa, in base all’evento che di verifica per primo.
    E.5.1.1Timepoint(s) of evaluation of this end point
    PFS Analysis/First OS Analysis: ~ 20 months after trial starts (when all subjects are enrolled, 230 PFS events and ~123 OS events are observed).
    Analisi PSF/analisi sopravvivenza globale: circa 20 mesi dopo l’inizio dello studio (quando tutti i soggetti sono stati arruolati, e sono stati osservati 230 eventi PFS e circa 123 OS).
    E.5.2Secondary end point(s)
    1. Compare the Overall Survival (OS).
    2. Evaluate Overall Response Rate (ORR) and Disease Control Rate (DCR) as assessed by CAC blinded central review and as per investigator
    assessment using IMWG criteria or EBMT criteria for minor response only and Duration of Response (DOR) as assessed by CAC blinded central review and as per investigator assessment using IMWG criteria
    3. Compare the Progression Free Survival (PFS) as assessed by the investigator using IMWG criteria between treatment arms.
    4. To evaluate the safety and tolerability in both treatment arms.
    1. Confrontare la sopravvivenza globale (OS).
    2. Valutare il tasso di risposta complessiva (ORR), il tasso di controllo della malattia (DCR) valutata dall’analisi centrale in cieco del CAC e dello sperimentatore mediante i criteri IMWG o EBMT solo per risposte minori e la durata della risposta (DOR) valutata dall’analisi centrale in cieco del CAC e dello sperimentatore mediante i criteri IMWG.
    3. Confrontare la sopravvivenza libera da progressione tra i bracci di trattamento valutata dallo sperimentatore mediante i criteri IMWG.
    4. Valutare la sicurezza e la tollerabilità in entrambi i bracci di trattamento.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. An interim safety analysis will take place after 15 subjects in each treatment arm have completed 1 cycle of therapy.
    2. Final OS Analysis: ~ 10 mos after main PFS analysis or ~ 185 OS events, whichever comes first.
    1. Verrà eseguita un’analisi ad interim di sicurezza quando 15 pazienti in ciascun braccio avranno completato il primo ciclo di terapia.
    2. Analisi OS finale: circa 10 mesi l’analisi PSF o quando si verificano circa 185 eventi OS in base all’evento che di verifica per primo.
    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 Yes
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    France
    Germany
    Israel
    Italy
    Japan
    Spain
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    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 No
    F.1.1Number of subjects for this age range: 1
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 75
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 225
    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 Yes
    F.3.3.2Women of child-bearing potential using contraception No
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 75
    F.4.2.2In the whole clinical trial 300
    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.
    Standard di cura.
    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 Decision2016-02-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-02-25
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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