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    Summary
    EudraCT Number:2010-021557-40
    Sponsor's Protocol Code Number:MM-Rel
    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:2012-03-14
    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 number2010-021557-40
    A.3Full title of the trial
    A phase III trial comparing bortezomib, cyclophosphamide and dexamethasone versus lenalinomide cyclophosphamide and dexamethasone in patients with multiple myeloma at first relapse
    STUDIO DI FASE III DI CONFRONTO TRA BORTEZOMIB, CICLOFOSFAMIDE E DESAMETASONE RISPETTO A LENALIDOMIDE, CICLOFOSFAMIDE E DESAMETASONE IN PAZIENTI CON MIELOMA MULTIPLO IN PRIMA RICADUTA.
    A.3.2Name or abbreviated title of the trial where available
    MM-Rel
    MM-Rel
    A.4.1Sponsor's protocol code numberMM-Rel
    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 SponsorISTITUTO NAZIONALE PER LA CURA TUMORI
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportministero della salute
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationfondazione IRCCS INT Milano
    B.5.2Functional name of contact pointEmatologia TMO
    B.5.3 Address:
    B.5.3.1Street AddressVia Venezian,1
    B.5.3.2Town/ cityMilano
    B.5.3.3Post code20133
    B.5.3.4CountryItaly
    B.5.4Telephone number02.23903146
    B.5.5Fax number02.23903415
    B.5.6E-mailvittorio.montefusco@istitutotumori.mi.it
    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 VELCADE
    D.2.1.1.2Name of the Marketing Authorisation holderJANSSEN CILAG SpA
    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 Powder for solution for injection
    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 INNBortezomib
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.3Concentration number1.3
    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 SOLDESAM
    D.2.1.1.2Name of the Marketing Authorisation holderLAB.FARMACOLOGICO MILAN.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 Oral drops, solution
    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 INNDexamethasone
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name ENDOXAN BAXTER*INIET 1FL 500MG
    D.2.1.1.2Name of the Marketing Authorisation holderBAXTER SpA
    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 Powder for solution for injection
    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 INNCyclophosphamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.3Concentration number500
    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: 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 REVLIMID*21CPS 15MG
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE 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 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 INNrevlimid
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number15
    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: 5
    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 REVLIMID*21CPS 10MG
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE 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 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 INNrevlimid
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number10
    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: 6
    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 ENDOXAN BAXTER*INIET 1FL 500MG
    D.2.1.1.2Name of the Marketing Authorisation holderBAXTER SpA
    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 Powder for solution for injection
    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 INNCyclophosphamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.3Concentration number500
    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: 7
    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 SOLDESAM
    D.2.1.1.2Name of the Marketing Authorisation holderLAB.FARMACOLOGICO MILAN.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 Oral drops, solution
    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 INNDexamethasone
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number20
    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: 8
    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 REVLIMID*21CPS 5MG
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE 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 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 INNrevlimid
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number10
    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
    Multiple mieloma
    Mieloma multiplo
    E.1.1.1Medical condition in easily understood language
    The disease of multiple myeloma is caracterized by a production of a abnormal monoclonal protein in serum and or urine
    Il Mieloma Multiplo e' una malattia del midollo osseo caratterizzata dalla produzione di una proteina anomala (componente monoclonale) a livello del siero e/o delle urine
    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 PT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    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
    In the present clinical study, we are planning to evaluate if the combination of bortezomib (Velcade)-cyclophosphamide-dexamethasone (VCD) is superior to the combination lenalidomide (Revlimid)-cyclophosphamide-dexamethasone (RCD) in MM patients with relapsed/refractory MM.The primary objective of this study is to compare the CR and VGPR rate at 6 weeks after the end of consolidation in patients treated with VCD versus RCD.
    Nel nostro studio prospettico, abbiamo intenzione di rispondere ad alcuni quesiti clinici: 1. se nella terapia di seconda linea sia piu` attiva una combinazione di farmaci contenente Bortezomib o Lenalidomide; 2. se l’aggiunta di Ciclofosfamide possa migliorare il numero di CR e, quindi, ridurre il tempo al fallimento del trattamento. L’obiettivo principale dello studio e` confrontare il tasso di CR e VGPR a 6 settimane dal termine della fase di consolidamento in pazienti trattati con VCR rispetto a quelli che hanno ricevuto RCD.
    E.2.2Secondary objectives of the trial
    • Treatment-related mortality (TRM) • Progression free survival (PFS) • Time to treatment failure (TTF) • Treatment free interval (TFI) • Overall survival (OS) • Treatment discontinuation rate • Stringent CR • Phenotypic remission • Molecular remission • Comparison of bone marrow cytology and biopsy
    Valutazione di: - mortalita' correlate al trattamento (TRM) -Sopravvivenza libera da progressione (PFS) -Tempo al fallimento del trattamento (TTF) -Intervallo libero da terapia (TFI) -Sopravvivenza globale (OS) -Tasso di CR stringenti (sCR) -Tasso di interruzione del trattamento -Remissioni immunofenotipiche -remissioni molecolari -Confronto tra significativita' della alutazione citologica di malattia rispetto a quella istologica
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    OTHER SUBSTUDIES:


    ALTRI SOTTOSTUDI:
    E’ previsto l’invio di un campione di sangue e di midollo al momento dell’arruolamento ed in momenti successivi dello studio. Va sottolineato come i prelievi di midollo osseo vengano effettuati in concomitanza delle normali valutazioni con finalita' diagnostica, per cui non viene effettuato un prelievo dedicato all’ottenimento di materiale per uso sperimentale. I campioni verranno centralizzati presso il laboratorio della SC Ematologia della Fondazione IRCCS Istituto Nazionale Tumori di Milano.

    E.3Principal inclusion criteria
    • age between 18 and 75 years old ; • written informed consent; • multiple myeloma at first active relapse; • Karnofsky performance status > 60%; • measurable disease: secretory MM defined as a serum monoclonal IgG of ≥ 1 g/dL or serum monoclonal IgA, IgD or IgE ≥ 0.5 g/dL or urine light-chain excretion of >200 mg/24 hours; • absolute neutrophil count ≥ 1000/microl, platelets > 75.000/microl; • no severe organ disfunctions; • life expectancy > 6 months.
    • Eta` compresa tra i 18 e 75 anni; • Firma del consenso informato; • Mieloma multiplo in prima ricaduta con indicazione al trattamento; • Score di Karnofsky ≥ 60%; • Malattia misurabile: MM secernente definito con la presenza di IgG monoclonale ≥ 1 gr/dL, o IgA, IgD, IgE ≥ 0.5 gr/dL, o proteinuria di Bence Jones &gt; 200 mg/24 ore; • Valore assoluto dei neutrofili ≥1000/microL e delle piastrine ≥75000/microL; • Assenza di insufficienze d’organo clinicamente rilevanti; • Aspettativa di vita &gt;6 mesi. I pazienti di eta` ≤65 anni, che sono stati precedentemente trattati con un solo autotrapianto, che hanno avuto una durata di risposta &gt;2 anni e che possiedono un adeguato numero di cellule staminali emopoietiche criopreservate possono ricevere un secondo autotrapianto al termine del programma di trattamento, cioe` sei settimane dopo l’ultimo ciclo di consolidamento. Il medico curante dovra` dichiarare al momento dell’arruolamento nello studio la volonta` di procedere successivamente ad autotrapianto per permettere la stratificazione dei pazienti.
    E.4Principal exclusion criteria
    • central nervous system localization; • pulmonary embolism in the last 3 months; • ongoing maintenance treatment with lenalinomide; • previous exposure to bortezomib and/or lenalidomide in the first line treatment, unless the patient has obtained at least a response >PR extended for >12 months; • grade 3-4 peripheral neuropathy; • any active, uncontrolled infection; • positive serologic markers for human immunodeficiency virus (HIV), active hepatitis B virus (HBV DNA positivity), and hepatitis C virus (HCV RNA positivity) infection; • Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study; • uncontrolled diabetes mellitus; • serum bilirubin levels > 2 the upper normal limit; • clearance of creatinine < 30 ml/min; • DLCO < 50%; • ejection fraction < 45% (or myocardial infarction in the last 12 months); • pregnancy or lactation; • patient not agreeing to take adequate contraceptive measures during the study, if at risk; • psychiatric disease; • active secondary malignancy; • inability to comply with medical therapy or follow-up.
    Localizzazione di malattia al sistema nervosa centrale; • Embolia polmonare nei 3 mesi precedenti; • Prosecuzione di mantenimento con Lenalidomide; • Precedente trattamento nella terapia di prima linea con cicli contenenti Bortezomib e/o Lenalidomide, eccetto che nei casi in cui il paziente abbia ottenuto almeno una risposta parziale che sia durata ≥ 12 mesi; • Neuropatia di grado III-IV; • Ogni infezione attiva non controllata; • Positivita` per i marker sierologici di HIV, virus dell’epatite B (positivita` per HBV DNA) e virus dell’epatite C (positivita` di HCV RNA); • Ogni condizione clinica severa, inclusa la presenza di alterazioni laboratoristiche, che possano esporre il paziente ad un rischio inaccettabile se arruolato nello studio o possano costituire un elemento di confondimento nell’analisi dei dati; • Diabete mellito non controllato; • Bilirubina sierica &gt;2 volte il limite massimo; • Clearance della creatinina &lt;30 mL/min; • DLCO &lt;50%; • Frazione di eiezione sierica &lt;45% o infarto miocardico nei 12 mesi precedenti; • Stato di gravidanza o di allattamento; • Rifiutarsi di utilizzare adeguati metodi contraccettivi durante lo studio; • Malattia psichiatrica; • Seconda neoplasia attiva; • Incapacita` a seguire la terapia medica o le procedure del follow-up.
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective of this study is to compare the CR and VGPR rate at 6 weeks after the end of consolidation in patients treated with VCD versus RCD.
    L’obiettivo principale dello studio e` confrontare il tasso di CR e VGPR a 6 settimane dal termine della fase di consolidamento in pazienti trattati con VCR rispetto a quelli che hanno ricevuto RCD.
    E.5.1.1Timepoint(s) of evaluation of this end point
    For the primary endpoint, the study will be concluded when the last enrolled patient will be observed for 6 weeks
    Per l`end-point primario , lo studio sara' concluso quando l`ultimo paziente arruolato sara' osservato per 6 settimane
    E.5.2Secondary end point(s)
    Secondary endpoint: • Treatment-related mortality (TRM) • Progression free survival (PFS) • Time to treatment failure (TTF) • Treatment free interval (TFI) • Overall survival (OS) • Treatment discontinuation rate • Stringent CR • Phenotypic remission • Molecular remission • Comparison of bone marrow cytology and biopsy
    Valutazione di: - mortalita` correlate al trattamento (TRM) -Sopravvivenza libera da progressione (PFS) -Tempo al fallimento del trattamento (TTF) -Intervallo libero da terapia (TFI) -Sopravvivenza globale (OS) -Tasso di CR stringenti (sCR) -Tasso di interruzione del trattamento -Remissioni immunofenotipiche -remissioni molecolari -Confronto tra significativita` della alutazione citologica di malattia rispetto a quella istologica
    E.5.2.1Timepoint(s) of evaluation of this end point
    The efficacy of experimental therapy will be assessed during the experimental phase lasting for 3 years. Surviving patients will be included into an observational cohort and followed for 3 additional years to assess the long-term effect of experimental treatments on hard end-points like all-cause mortality as well as on secondary endpoints
    Studio Sperimentale: 2 anni di tempo di arruolamento piu' un anno di follow-up per l’ultimo paziente arruolato per valutare l’end-point principale. Studio Osservazionale: alla fine della fase sperimentale, i pazienti saranno inclusi in uno studio prospettico osservazionale per un minimo di 3 anni per valutare la prognosi a lungo termine, i.e. PFS, TTF, TFI and OS.
    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 No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    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 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 concerned20
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    Alla fine della fase sperimentale, i pazienti saranno inclusi in uno studio prospettico osservazionale per un minimo di 3 anni per valutare la prognosi a lungo termine e gli obiettivi secondari dello studio.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned 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.1.3Elderly (>=65 years) Yes
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-03-14. Yes
    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 state200
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-03-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-09-23
    P. End of Trial
    P.End of Trial StatusCompleted
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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