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    Summary
    EudraCT Number:2010-023772-71
    Sponsor's Protocol Code Number:C16006
    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:2012-03-09
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2010-023772-71
    A.3Full title of the trial
    An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of MLN9708, a Next-Generation Proteasome Inhibitor, Administered in Combination with a Standard Care Regimen of Melphalan and Prednisone in Patients With Newly-Diagnosed Multiple Myeloma Requiring Systemic Treatment.
    Studio di fase 1/2 in aperto, con aumento della dose, condotto sulla formulazione orale di MLN9708, un inibitore del proteasoma di prossima generazione, somministrato in associazione con un trattamento standard a base di melfalan e prednisone in pazienti con mieloma multiplo appena diagnosticato che necessita di trattamento sistemico.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/ 2 Study of the Oral Form of MLN9708 with Melphalan and Prednisone for Patients with Newly Diagnosed Multiple Myeloma
    Studio di fase 1/2 sulla formulazione orale di MLN9708 con melfalan e prednisone in pazienti con mieloma multiplo appena diagnosticato.
    A.3.2Name or abbreviated title of the trial where available
    C16006
    C16006
    A.4.1Sponsor's protocol code numberC16006
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01335685
    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 SponsorMILLENNIUM PHARMACEUTICALS, 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 supportMillennium Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMillennium Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointDrug Information Call Center
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne St
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post code02139
    B.5.3.4CountryItaly
    B.5.4Telephone number0015107402412
    B.5.5Fax number0018008816092
    B.5.6E-mailmedical@mlnm.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 nameMLN9708
    D.3.2Product code MLN9708
    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 INNNA
    D.3.9.1CAS number 1239908-20-3
    D.3.9.2Current sponsor codeMLN9708
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 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 nameMLN9708
    D.3.2Product code MLN9708
    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 INNNA
    D.3.9.1CAS number 1239908-20-3
    D.3.9.2Current sponsor codeMLN9708
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    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: 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 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 nameMLN9708
    D.3.2Product code MLN9708
    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 INNNA
    D.3.9.1CAS number 1239908-20-3
    D.3.9.2Current sponsor codeMLN9708
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000
    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
    Newly diagnosed multiple myeloma
    Multiple mieloma di nuova diagnosi
    E.1.1.1Medical condition in easily understood language
    Type of cancer of the white blood cells
    Tipo di tumore dei globuli bianchi
    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 SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 2: To determine the combined response rate of CR + VGPR during the induction therapy period following a twice weekly administration of oral MLN9708 on Days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle when added to standard care MP on Days 1 through 4 of every cycle To determine the combined response rate of CR + VGPR during the induction therapy period following a once weekly administration of oral MLN9708 on Days 1, 8, and 15 of a 28-day cycle when added to standard care MP on Days 1 through 4 of every cycle
    Phase 2: To determine the combined response rate of CR + VGPR during the induction therapy period following a twice weekly administration of oral MLN9708 on Days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle when added to standard care MP on Days 1 through 4 of every cycle To determine the combined response rate of CR + VGPR during the induction therapy period following a once weekly administration of oral MLN9708 on Days 1, 8, and 15 of a 28-day cycle when added to standard care MP on Days 1 through 4 of every cycle
    E.2.2Secondary objectives of the trial
    To determine the time to response during the induction therapy period To evaluate the duration of response (DOR) for patients who responded XML File Identifier: WoITorNlHdIXG7KRVAukHdNB5Js= Page 18/35 during the induction therapy period To determine ORR during the induction therapy period and through the entire study To assess the time to progression (TTP) To evaluate time to next therapy and treatment-free interval To evaluate the progression-free survival (PFS) rate To evaluate the overall survival (including 1-year survival rate) To determine the safety profile of MLN9708 To evaluate changes in quality of life (QOL)
    To determine the time to response during the induction therapy period To evaluate the duration of response (DOR) for patients who responded XML File Identifier: WoITorNlHdIXG7KRVAukHdNB5Js= Page 18/35 during the induction therapy period To determine ORR during the induction therapy period and through the entire study To assess the time to progression (TTP) To evaluate time to next therapy and treatment-free interval To evaluate the progression-free survival (PFS) rate To evaluate the overall survival (including 1-year survival rate) To determine the safety profile of MLN9708 To evaluate changes in quality of life (QOL)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female patient for whom standard MP treatment is indicated and who is not a candidate for HDT-SCT for 1 of the following reasons: The patient is 65 years of age or older. The patient is less than 65 years of age but has significant comorbid condition(s) that are likely to have a negative impact on tolerability of HDT-SCT. 2. Symptomatic MM or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria 3. Patients must have measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein ≥ 1 g/dL (≥ 10 g/L) Urine M-protein ≥ 200 mg/24 hours Serum free light chain assay: involved free light chain level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum free light chain ratio is abnormal 4. Patients must meet the following clinical laboratory criteria within 3 days before the first dose of study treatment to be enrolled in the study: Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to study drug dosing. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN. Calculated creatinine clearance ≥ 30 mL/min 5. ECOG performance status of 0 to 2 6. Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse 7. Male patients, even if surgically sterilized (ie, status postvasectomy), who: Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study treatment, OR Agree to completely abstain from heterosexual intercourse Male patients must agree to not father a child and agree to use a latex condom during therapy and for 4 months after the last dose of study treatment, even if they have had a successful vasectomy, if their partner is of childbearing potential. 8. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
    1. Pazienti di sesso maschile o femminile per i quali è indicato il trattamento MP standard e non candidati a HDT-SCT per uno dei seguenti motivi: • Il paziente ha un’età pari o superiore a 65 anni. • Il paziente ha meno di 65 anni ma presenta significative condizioni di comorbilità che possono avere un impatto negativo sulla tollerabilità dell’HDT-SCT. 2. MM sintomatico o mieloma asintomatico con danno agli organi correlato al mieloma diagnosticato secondo i criteri standard (vedere Sezioni 15.1 e 15.2) 3. I pazienti devono presentare una malattia misurabile definita tramite almeno una delle tre seguenti misurazioni: • Proteina M nel siero ≥ 1 g/dL (≥ 10 g/L) • Proteina M nell’urina ≥ 200 mg/24 ore • Analisi delle catene libere leggere nel siero: livello catene libere leggere coinvolte ≥ 10 mg/dL (≥ 100 mg/L), a condizione che il rapporto delle catene libere leggere nel siero sia anormale 4. Per poter essere arruolati nello studio, i pazienti devono soddisfare i seguenti criteri del laboratorio clinico nei 3 giorni precedenti la prima dose del farmaco dello studio: • Conta dei neutrofili (ANC) ≥ 1.000/mm3 e conta delle piastrine ≥ 75.000/mm3. Non sono consentite trasfusioni piastriniche che portino i pazienti a soddisfare i criteri di idoneità nei 3 giorni precedenti alla somministrazione del farmaco dello studio. • Bilirubina totale ≤ 1,5 volte il limite superiore della norma (ULN). • Alanina aminotransferasi (ALT) e aspartato aminotransferasi (AST) ≤ 3 volte l’ULN. • Clearance della creatinina calcolata ≥ 30 mL/min (vedere sezione 15.2). 5. Performance status secondo l’ECOG da 0 a 2 (vedere sezione 15.4). 6. Pazienti di sesso femminile: • In post-menopausa da almeno 1 anno prima della visita di screening OPPURE • Chirurgicamente sterili OPPURE • Se fertili, accettino di adottare contemporaneamente 2 metodi contraccettivi efficaci, dal momento della firma del consenso informato fino a 30 giorni dopo l’ultima dose del farmaco dello studio OPPURE accettino di astenersi completamente dall’avere rapporti eterosessuali 7. Pazienti di sesso maschile, anche se chirurgicamente sterilizzati (post-vasectomia): • Accettino di praticare una contraccezione a barriera efficace durante tutto il periodo dello studio e fino a 4 mesi dopo la somministrazione dell’ultima dose del farmaco dello studio OPPURE • Accettino di astenersi completamente dall’avere rapporti eterosessuali • I pazienti di sesso maschile, nel caso la loro partner sia fertile, devono accettare di non procreare e di usare un profilattico in lattice durante la terapia e nei 4 mesi successivi alla somministrazione dell’ultima dose del farmaco dello studio, anche se sono stati sottoposti a vasectomia con esito positivo. 8. Deve essere presentato il consenso volontario scritto prima dell’attuazione di qualunque procedura correlata allo studio non appartenente alle cure mediche standard, con la consapevolezza che il consenso può essere ritirato dal paziente in qualunque momento senza conseguenze sulle future cure mediche.
    E.4Principal exclusion criteria
    1. Peripheral neuropathy ≥ Grade 2 on clinical examination during the screening period. 2. Female patients who are lactating or pregnant. 3. Major surgery within 14 days before the first dose of study drug. (Note: kyphoplasty or vertebroplasty is not considered major surgery.) 4. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug. 5. Diarrhea >Grade 1, based on the NCI CTCAE grading, in the absence of antidiarrheals. 6. Prior systemic therapy for MM, including investigational drugs. Prior treatment with corticosteroids or localized radiation therapy does not disqualify the patient (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone, a total of which can be given in a 2-week period. 7. Radiotherapy within 14 days before the first dose of study treatment. 8. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment. 9. Central nervous system involvement. 10. Diagnosis of smoldering MM, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. 11. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. 12. QTc > 470 msec on a 12-lead ECG obtained during the Screening period. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG. 13. Known or suspected human immunodeficiency virus (HIV) positive. 14. Known or suspected hepatitis B surface antigen-positive status orknown or suspected active hepatitis C infection. 15. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 16. Known allergy to any of the study medications, their analogues, or excipients in the various formulations. 17. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing. 18. Diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
    1. Neuropatia periferica ≥ grado 2 all’esame clinico durante il periodo di screening. 2. Donne in gravidanza o allattamento. 3. Intervento chirurgico importante nei 14 giorni precedenti la prima dose del farmaco dello studio. (Nota: la chifoplastica o la vertebroplastica non sono considerate interventi chirurgici importanti). 4. Infezione che necessiti di terapia antibiotica sistemica o altra grave infezione nei 14 giorni precedenti la prima dose del farmaco dello studio. 5. Crisi diarroica &gt; grado 1, in base alla classificazione NCI CTCAE, in assenza di antidiarroici. 6. Precedente terapia sistemica per MM, compresi farmaci sperimentali. Il precedente trattamento con corticosteroidi o radioterapia localizzata non esclude il paziente (la dose massima di corticosteroidi non dovrà aver superato l’equivalente di 160 mg di desametasone e il suo totale potrà essere stato somministrato in un periodo di 2 settimane [per un elenco di dosi di steroidi equivalenti, vedere la sezione 15.5]). 7. Radioterapia nei 14 giorni precedenti la prima dose del farmaco dello studio. 8. Trattamento sistemico con potenti inibitori di CYP1A2 (fluvoxamina, enoxacina), potenti inibitori di CYP3A (claritromicina, telitromicina, itraconazolo, voriconazolo, ketoconazolo, nefazodone, posaconazolo) o potenti induttori di CYP3A (rifampina, rifapentina, rifabutina, carbamazepina, fenitoina, fenobarbital) o l’uso di Ginkgo biloba o iperico (erba di San Giovanni) nei 14 giorni precedenti la prima dose di farmaco dello studio. 9. Coinvolgimento del sistema nervoso centrale. 10. Diagnosi di MM a progressione lenta, macroglobulinemie di Waldenstrom, sindrome POEMS (polineuropatia, organomegalia, endocrinopatia, gammopatia monoclonale e alterazioni cutanee), leucemia plasmacellulare, amiloidosi primaria, sindrome mielodisplastica o sindrome mieloproliferativa (vedere sezione 15.2) 11. Evidenza di condizioni cardiovascolari correnti non controllate, tra cui ipertensione non controllata, aritmie cardiache non controllate, insufficienza cardiaca congestizia sintomatica, angina instabile o infarto miocardico negli ultimi 6 mesi. 12. QTc &gt; 470 msec in un ECG a 12 derivazioni ottenuto durante il periodo di screening. Se un valore indicato dalla macchina è superiore a questo valore, l’ECG deve essere analizzato da un medico qualificato e confermato da un successivo ECG. 13. Positività accertata o sospetta al virus dell’immunodeficienza umana (HIV). 14. Positività accertata o sospetta all’antigene di superficie del virus dell’epatite B o infezione attiva, accertata o sospetta, da virus dell’epatite C. 15. Qualunque grave patologia medica o psichiatrica che potrebbe, secondo il giudizio dello sperimentatore, interferire potenzialmente con il completamento del trattamento previsto dal presente protocollo. 16. Allergia accertata verso uno dei farmaci dello studio, analoghi o eccipienti contenuti nelle varie formulazioni. 17. Malattia gastrointestinale (GI) accertata o intervento GI che potrebbe interferire con l’assorbimento orale o con la tolleranza del farmaco dello studio, tra cui la difficoltà di deglutizione. 18. Diagnosi o trattamento di altro tumore maligno nei 2 anni precedenti la prima dose o diagnosi precedente di altro tumore maligno con evidenza di malattia residua. I pazienti con cancro della pelle non melanoma o carcinoma in situ di qualunque tipo non sono esclusi se sono stati sottoposti a resezione completa.
    E.5 End points
    E.5.1Primary end point(s)
    Combined response rate of CR + VGPR in patients treated with MLN9708 when added to a standard care regimen of MP during the induction period
    Tasso di risposta combinata di CR (risposta completa) + VGPR (risposta parziale molto buona) in pazienti trattati con MLN9708 con aggiunta di un regime di cura standard di melphelan durante il periodo di induzione.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Arm A Induction period: End of each 42 day cycle for up to 9 cycles. Arm B Induction Period: End of each 28 day cycle up to cycle 6 (and for every 2 cycles thereafter if in phase 1 for up to 12 cycles).
    Braccio A Periodo di induzione: fine di ogni ciclo di 42 giorni fino a 09 cicli.
    Braccio B Periodo di induzione: fine di ogni ciclo di 28 giorni fino al ciclo 6 (e per ogni 2 cicli successivamente se in fase 1 fino a 12 cicli).
    E.5.2Secondary end point(s)
    To determine the time to response during the induction therapy period To evaluate the duration of response (DOR) for patients who responded during the induction therapy period To determine ORR during the induction therapy period and throughout the entire study To assess the time to progression (TTP)
    Per determinare il tempo di risposta durante il periodo di terapia di induzione
    Per valutare la durata della risposta(DOR) per pazienti responsivi durante il periodo di induzione della terapia Per determinare il tasso di risposta complessivo (ORR)durante il periodo di induzione della terapia e attraverso l' intero studio. Per valutare il tempo di progressione(TTP.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Arm A Induction period: End of each 42 day cycle for up to 9 cycles. Arm B Induction Period: End of each 28 day cycle up to cycle 6 (and for every 2 cycles thereafter if in phase 1 for up to 12 cycles). Arm A&B Maintenance period: Every 2 cycles (28 day cycle) for up to 12 cycles
    Braccio A Periodo di induzione: fine di ogni ciclo di 42 giorni fino a 09 cicli.
    Braccio B Periodo di induzione: fine di ogni ciclo di 28 giorni fino al ciclo 6 (e per ogni 2 cicli successivamente se in fase 1 fino a 12 cicli).
    Braccio A e B Period di mantenimento: Ogni 2 cicli (ciclo di 28 giorni) fino a 12 cicli
    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 Yes
    E.6.10Pharmacogenetic Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    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 No
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Canada
    Russian Federation
    United States
    E.8.7Trial has a data monitoring committee No
    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
    Last patient, last visit.
    ultima visita dell' ultimo paziente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months72
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months72
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 113
    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 state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 98
    F.4.2.2In the whole clinical trial 163
    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)
    not applicable
    non applicabile
    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 Decision2012-06-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-02-06
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2014-06-10
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