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    Summary
    EudraCT Number:2016-000860-40
    Sponsor's Protocol Code Number:CC-220-MM-001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-05-17
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2016-000860-40
    A.3Full title of the trial
    A PHASE 1B/2A MULTICENTER, OPEN-LABEL, DOSE-ESCALATION STUDY TO DETERMINE THE MAXIMUM TOLERATED DOSE, ASSESS THE SAFETY AND TOLERABILITY, PHARMACOKINETICS AND PRELIMINARY EFFICACY OF CC-220 MONOTHERAPY AND IN COMBINATION WITH DEXAMETHASONE IN SUBJECTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA
    ESTUDIO DE FASE IB/IIA ABIERTO, DE ESCALADA DE DOSIS Y MULTICÉNTRICO PARA DETERMINAR LA DOSIS MÁXIMA TOLERADA Y EVALUAR LA SEGURIDAD Y LA TOLERABILIDAD, LA FARMACOCINÉTICA Y LA EFICACIA PRELIMINAR DE CC-220 EN MONOTERAPIA Y EN COMBINACIÓN CON DEXAMETASONA EN SUJETOS CON MIELOMA MÚLTIPLE RECIDIVANTE Y RESISTENTE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to decide what is the highest dose of CC-220 to take alone and with dexamethasone to assess the side effects, effectiveness and how the body deals with the drug in patients with multiple myeloma that recurs or is resistant to already tried medicines by patients.
    Un estudio para decidir cuál es la dosis más alta de CC-220 para tomar en solitario y con dexametasona para evaluar los efectos secundarios, la eficacia y la reacción del cuerpo al fármaco en los pacientes con mieloma múltiple recurrente o es resistente a medicamentos previamente probados.
    A.4.1Sponsor's protocol code numberCC-220-MM-001
    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 SponsorCelgene Corporation
    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 supportCelgene Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCelgene Corporation
    B.5.2Functional name of contact pointClinicalTrialDisclosure
    B.5.3 Address:
    B.5.3.1Street Address9224 Indian Creek Parkway, Suite 900
    B.5.3.2Town/ cityOverland Park, Kansas
    B.5.3.3Post code66210
    B.5.3.4CountryUnited States
    B.5.4Telephone number34914229000
    B.5.5Fax number19132660394
    B.5.6E-mailClinicalTrialDisclosure@celgene.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 nameCC-220
    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 INNCC-220
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.15
    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 nameCC-220
    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 INNCC-220
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.30
    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 nameCC-220
    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 INNCC-220
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.45
    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 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 Dexamethasone tablets BP 2 mg
    D.2.1.1.2Name of the Marketing Authorisation holderAspen Pharma Trading Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 namedexamethasone
    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 INNdexamethasone
    D.3.9.3Other descriptive nameDEXAMETHASONE PH. EUR.
    D.3.9.4EV Substance CodeSUB170672
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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 Dexamethasone-ratiopharm 4 mg tablets
    D.2.1.1.2Name of the Marketing Authorisation holderRatiopharm GmbH
    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 nameDexamethasone
    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 INNDEXAMETHASONE
    D.3.9.2Current sponsor codedexamethason-ratiopharm 4 mg
    D.3.9.4EV Substance CodeSUB07017MIG
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    RELAPSED AND REFRACTORY MULTIPLE MYELOMA
    MIELOMA MÚLTIPLE RECIDIVANTE Y RESISTENTE
    E.1.1.1Medical condition in easily understood language
    Multiple Myeloma that recurs or is resistant to already tried medicines by patients
    Mieloma múltiple recurrente o resistente a medicamentos previamente probados
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10067095
    E.1.2Term Multiple myeloma progression
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level HLT
    E.1.2Classification code 10028229
    E.1.2Term Multiple myelomas
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the maximum tolerated doses (MTDs) of CC-220 as monotherapy (MonoT) and in combination with dexamethasone (DEX) (DoubleT) in subjects with RRMM
    Determinar las dosis máximas toleradas (DMT) de CC 220 en monoterapia (MonoT) y en combinación con DEX (DobleT) en sujetos con MMRR.
    E.2.2Secondary objectives of the trial
    ·To evaluate the safety of CC-220 as MonoT and in combination with DEX (DoubleT) in subjects with RRMM
    ·To estimate the preliminary efficacy of CC-220 as MonoT and in combination with DEX (DoubleT) in subjects with RRMM
    ·To evaluate the pharmacokinetics (PK) of CC-220 in subjects with RRMM
    ·Evaluar la seguridad de CC-220 en MonoT y en combinación con DEX (DobleT) en sujetos con MMRR.
    ·Estimar la eficacia preliminar de CC-220 en MonoT y en combinación con DEX (DobleT) en sujetos con MMRR.
    ·Evaluar la farmacocinética de CC-220 en pacientes con MMRR.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must satisfy the following criteria to be enrolled in the study:
    1. Subject is ? 18 years of age at the time of signing the informed consent form (ICF)
    2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
    3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements
    4. Subjects must have a documented diagnosis of MM and have measurable disease by serum and/or urine protein electrophoresis (sPEP or uPEP): sPEP ?0.5 g/dL or uPEP ?200 mg/24 hours
    5. All subjects must have received at least 2 prior myeloma regimens (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen)
    6. All subjects must have received prior treatment with at least 2 consecutive cycles of a lenalidomide or pomalidomide-containing regimen
    7. All subjects must have received prior treatment with at least 2 consecutive cycles of a proteasome inhibitor or a proteasome inhibitor-containing regimen
    8. All subjects must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
    9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
    10. Females of childbearing potential (FCBP) must:
    a. Have a negative pregnancy test as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after the end of IP. This applies even if the subject practices true abstinence* from heterosexual contact.
    b. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
    11. Male subjects must:
    a. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.
    * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]
    12. Males must agree to refrain from donating sperm while on CC-220 and for 90 days after discontinuation from IP.
    13. All subjects must agree to refrain from donating blood while on IP and for 90 days after discontinuation from IP.
    1. El paciente tiene ?18 años en el momento de la firma del formulario de consentimiento informado (FCI).
    2. El paciente debe comprender y firmar de forma voluntaria un FCI antes de que se realice cualquier evaluación o procedimiento relacionado con el estudio.
    3. El paciente es capaz y tiene la voluntad de cumplir con el calendario de visitas del estudio y otros requisitos del protocolo.
    4. Los pacientes deben tener un diagnóstico documentado de MM y presentar una enfermedad cuantificable mediante electroforesis de proteínas séricas y/o de orina (EFPs o EFPo): EFPs ?0,5 g/dl o EFPo ?200 mg/24 horas.
    5. Todos los pacientes deben haber recibido al menos 2 regímenes terapéuticos previos para el mieloma (nota: la inducción con o sin trasplante de médula ósea y con o sin tratamiento de mantenimiento se considera un único régimen terapéutico).
    6. Todos los pacientes deben haber recibido tratamiento previo con al menos 2 ciclos consecutivos de un régimen terapéutico que contenga lenalidomida o pomalidomida.
    7. Todos los pacientes deben haber recibido tratamiento previo con al menos 2 ciclos consecutivos de un régimen terapéutico con un inhibidor de proteosomas o que contuviera un inhibidor de proteosomas.
    8. Todos los pacientes deben presentar una progresión de la enfermedad documentada a los 60 días o dentro del periodo de 60 días desde la última dosis de su último tratamiento para el mieloma.
    9. Puntuación del estado general de 0, 1 o 2 según el Eastern Cooperative Oncology Group (ECOG).
    10. Las mujeres potencialmente fértiles (MPF) deben:
    a. Presentar una prueba de embarazo negativa con la verificación del investigador antes de comenzar con el tratamiento del estudio. Aceptar someterse a pruebas de embarazo de forma regular durante el transcurso del estudio y una vez terminado el tratamiento con el PEI. Esto será así incluso si la participante practica la abstinencia total* de contacto heterosexual.
    b. Se ha de comprometer bien a la abstinencia total* de contacto heterosexual (que se debe revisar de forma mensual y con fuente documentada) o bien a aceptar el uso y ser capaz de cumplir con un método anticonceptivo eficaz sin interrupción, 28 días antes del inicio del tratamiento con el producto en investigación, durante el tratamiento del estudio (incluidas las suspensiones temporales de la dosis) y durante 28 días tras la suspensión definitiva del tratamiento del estudio.
    11. Los pacientes varones deben:
    a. Practicar abstinencia total* (que se debe revisar de forma mensual) o aceptar el uso de preservativo durante las prácticas sexuales con una mujer embarazada o potencialmente fértil mientras participe en el estudio, durante las suspensiones temporales de la dosis y durante al menos 28 días tras la suspensión definitiva del producto en investigación, incluso aunque se haya sometido con éxito a una vasectomía.
    * La abstinencia total es aceptable si está en consonancia con el estilo de vida preferido y habitual del paciente. (La abstinencia periódica [p. ej., métodos de Ogino, de ovulación, sintotérmico o de posovulación] y el coitus interruptus no son métodos anticonceptivos aceptables.)
    12. Los varones deben abstenerse de donar semen mientras estén en tratamiento con CC-220 y durante 90 días después de la suspensión definitiva del PEI.
    13. Todos los varones deben aceptar abstenerse de donar sangre mientras estén en tratamiento con el PEI y durante 90 días después de la suspensión definitiva del PEI.
    E.4Principal exclusion criteria
    The presence of any of the following will exclude a subject from enrollment:
    1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
    2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
    3. Subject has any condition that confounds the ability to interpret data from the study
    4. Subject has nonsecretory or oligosecretory multiple myeloma
    5. Subjects with Plasma Cell leukemia
    6. Any of the following laboratory abnormalities
    ·Absolute neutrophil count (ANC) <1,000/?L
    ·Hemoglobin <8 g/dL (<4.9 mmol/L)
    ·Platelet count <75,000/?L Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)
    ·Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ?2.0 x upper limit of normal (ULN)
    ·Serum total bilirubin and alkaline phosphatase >1.5 x ULN
    ·Subjects with serious renal impairment (24-hour creatinine clearance [CrCl] <50 mL/min) or requiring dialysis would be excluded
    7. Subjects with peripheral neuropathy ?Grade 2
    8. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220
    9. Subjects with a prior history of malignancies, other than MM, unless the subject has been free of the disease for ?5 years with the exception of the following noninvasive malignancies:
    ·Basal cell carcinoma of the skin
    ·Squamous cell carcinoma of the skin
    ·Carcinoma in situ of the cervix
    ·Carcinoma in situ of the breast
    ·Incidental histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative
    10. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide or DEX
    11. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-220 or DEX
    12. Subject has received any of the following within the last 14 days of initiating IP:
    ·Plasmapheresis
    ·Major surgery (as defined by the Investigator)
    ·Radiation therapy other than local therapy for MM associated bone lesions
    ·Use of any systemic myeloma drug therapy
    13, Subject has been treated with an investigational agent within 28 days or 5 half-lives (whichever is longer) of initiating IP
    14. Subject has any one of the following:
    ·Clinically significant abnormal electrocardiogram (ECG) finding at Screening
    ·Congestive heart failure (New York Heart Association Class III or IV)
    ·Myocardial infarction within 12 months prior to starting IP
    ·Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris
    15. Subject has current or prior use of immunosuppressive medication within 14 days prior to the first dose of IP. The following are exceptions to this criterion:
    ·Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection)
    ·Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent
    ·Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)
    16. Subject has taken a strong inhibitor or inducer of CYP3A4/5 at least one week prior to dosing and during the course of study and grapefruit or related products ?1 week prior to dosing and intends to eat these products throughout the study
    17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C
    18. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis
    19. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study
    1. El paciente tiene cualquier afección médica, anomalía de laboratorio o enfermedad psiquiátrica importante que pudiera impedir su participación en el estudio.
    2. El paciente presenta cualquier afección, incluida la presencia de anomalías de laboratorio, que lo expondría a un riesgo inaceptable si participase en el estudio.
    3. El paciente tiene cualquier afección que altera la capacidad para interpretar los datos del estudio.
    4. El paciente tiene mieloma múltiple no secretor u oligosecretor.
    5. Pacientes con leucemia de células plasmáticas.
    6. Cualquiera de las siguientes anomalías de laboratorio:
    · Recuento absoluto de neutrófilos (RAN) <1000/µl.
    · Hemoglobina <8 g/dl (<4,9 mmol/l).
    · Recuento de plaquetas <75 000/µl Calcio sérico corregido >13,5 mg/dl (>3,4 mmol/l).
    · Transaminasa glutámico oxalacética sérica (SGOT)/aspartato aminotransferasa (AST) o transaminasa glutámico pirúvica sérica (SGPT)/alanina aminotransferasa (ALT) ?2,0 veces el límite superior de la normalidad (LSN).
    · Bilirrubina total y fosfatasa alcalina en suero >1,5 veces el LSN.
    · Los pacientes con insuficiencia renal grave (aclaramiento de creatinina [CrCl] en 24 horas <50 ml/min) o que requieren diálisis serán excluidos.
    7. Pacientes con neuropatía periférica de grado ?2.
    8. Pacientes con enfermedad gastrointestinal que pueda alterar significativamente la absorción de CC-220.
    9. Pacientes con antecedentes de neoplasia maligna, aparte de MM, salvo que el paciente haya permanecido sin la enfermedad durante ?5 años, con excepción de las siguientes neoplasias malignas no invasivas:
    · Carcinoma basocelular de la piel.
    · Carcinoma de células escamosas de la piel.
    · Carcinoma in situ de cuello uterino.
    · Carcinoma in situ de mama.
    · Signos histológicos circunstanciales de cáncer de próstata como T1a o T1b usando la clasificación tumor/ganglio/metástasis (TNM) de tumores malignos o cáncer de próstata que se puede curar.
    10. El paciente tiene antecedentes de anafilaxia o hipersensibilidad a la talidomida, lenalidomida, pomalidomida o DEX.
    11. El paciente tiene hipersensibilidad conocida o sospecha de hipersensibilidad a los excipientes que contiene la formulación de CC-220 o DEX.
    12. El paciente ha recibido cualquiera de los siguientes tratamientos en los últimos 14 días anteriores al inicio del tratamiento con el PEI:
    · Plasmaféresis.
    · Cirugía mayor (según la definición del investigador).
    · Radioterapia, aparte de la terapia local para el MM asociada con lesiones óseas.
    · Uso de cualquier farmacoterapia sistémica para el mieloma.
    13. El paciente ha recibido tratamiento con un fármaco en investigación durante los 28 días o 5 semividas (lo que sea más largo) previos al inicio del tratamiento con el PEI.
    14. El paciente tiene cualquiera de las siguientes afecciones:
    · Signos anómalos en el electrocardiograma (ECG) clínicamente significativos en la selección.
    · Insuficiencia cardíaca congestiva (clase III o IV según la New York Heart Association).
    · Infarto de miocardio en los 12 meses previos al inicio del tratamiento con el PEI.
    · Angina de pecho inestable o mal controlada, incluida la variante de angina de pecho de Prinzmetal.
    15. El paciente usa actualmente o ha usado previamente medicación inmunodepresora en los 14 días previos a la primera dosis del PEI. Se aplicarán las siguientes excepciones a este criterio:
    · Esteroides intranasales, tópicos, inhalados e inyecciones locales de esteroides (p. ej., inyección intraarticular).
    · Corticosteroides sistémicos a dosis fisiológicas no superiores a 10 mg/día de prednisona o equivalente.
    · Esteroides como premedicación para reacciones de hipersensibilidad (p. ej., premedicación para tomografía axial computarizada [TAC]).
    16. El paciente ha tomado un inhibidor o inductor potente de CYP3A4/5 al menos una semana antes de la dosis y durante el transcurso del estudio, pomelo u otros productos relacionados ?1 semana antes del tratamiento y tiene la intención de tomar estos productos a lo largo del estudio.
    17. El paciente tiene una prueba positiva conocida para el virus de inmunodeficiencia humana (VIH), hepatitis B crónica o activa o hepatitis A o C activa.
    18. El paciente no es capaz o no está dispuesto a someterse a profilaxis para la tromboembolia que requiere el protocolo.
    19. El paciente es una mujer embarazada, en periodo de lactancia o que pretende quedarse embarazada durante su participación en el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Recommended Dose - Establish the maximum tolerated doses (MTDs) of CC-220 monotherapy and in combination with dexamethasone
    Establecer las dosis máximas toleradas (DMT) de CC-220 en monoterapia y en combinación con dexametasona.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The endpoint of MTD is estimated after cycle 1 for each subject in the dose escalation phase.

    Further details are available in the clinical study protocol and Table 4 - Table of Events page 39-42 of the protocol
    El criterio de valoración de DMT se estima después del ciclo 1 para cada sujeto en la fase de escalada de dosis.
    Más detalles están disponibles en el protocolo del estudio clínico y en la Tabla 4 - Calendario de actividades páginas 43-47 del protocolo.
    E.5.2Secondary end point(s)
    Safety - Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product
    Overall Response Rate - Tumor response, including progressive disease (PD) according to the International Myeloma Working Group Uniform Response Criteria (IMWG)
    Time to Response (TTR) - Time from enrollment to response (partial response [PR] or greater)
    Duration of Response - Time from the first documentation of response (PR or greater) to the first documentation of PD
    PK parameters - PK of CC-220 in plasma, eg, area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC0-?), maximum plasma concentration of drug (Cmax), time to Cmax (Tmax), terminal-phase elimination half life (t1/2), apparent total plasma clearance when dosed daily (CLss/F) and apparent total volume of distribution at steady state when dosed orally (Vss/F)
    Seguridad-Tipo, frecuencia, gravedad e intensidad de los acontecimientos adversos (AA) (y AA de interés especial) y relación de los AA con el producto en investigación.
    Tasa de respuesta global (TRG)-Respuesta tumoral, incluida la progresión de la enfermedad (PE) según los criterios uniformes de respuesta del International Myeloma Working Group (IMWG)
    Tiempo hasta la respuesta (ThR)-Tiempo desde la inclusión hasta la primera documentación de respuesta (respuesta parcial [RP] o superior).
    Duración de la respuesta (DdR)-Tiempo desde la primera documentación de respuesta (RP o superior) hasta la primera documentación de PE.
    Parámetros de FC-FC de CC-220 en plasma, por ejemplo, área bajo la curva de concentración frente al tiempo desde tiempo cero a tau, donde tau es el intervalo de administración de la dosis (ABC0-?), concentración plasmática máxima del fármaco (Cmáx), tiempo hasta la Cmáx (Tmáx), semivida de eliminación terminal (t1/2), aclaramiento plasmático total aparente cuando se administra diariamente (CLss/F) y volumen de distribución aparente en estado de equilibrio cuando se administra por vía oral (Vss/F).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety - Continuous until 28 days after the last dose of study medication.
    Overall response rate - Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Rajkumar, 2011)
    Time to response - Time from enrollment to the first documentation of response (partial response [PR] or greater)
    Duration of Response - Time from the first documentation of response (PR or greater) to the first documentation of PD
    Pharmacokinetics (intensive) - Day 8, 15 (pre-dose), 22 of Cycle 1, Day 8, 15 and 22 of Cycles 2-4.
    PK (sparse) - all pre-dose - Day 8, 15, 22 of Cycle 1, Day 8, 15 and 22 of Cycles 2-4.
    Further details are available Table 4 - Table of Events page 39-42 of the protocol
    Seguridad-continua hasta 28 días después de la última dosis de la medicación del estudio.
    Tasa global de respuesta-respuesta del tumor, incluyendo Progresion de la Enfermedad (PE) según el Grupo de Trabajo Internacional del Mieloma (IMWG) Criterios de Respuesta Uniforme (Rajkumar, 2011)
    Tiempo de respuesta-tiempo desde el reclutamiento hasta la primera respuesta (respuesta parcial [RP] o superior)
    Duración de la respuesta-Tiempo desde la primera respuesta (PR o superior) a la primera documentación de PE
    Farmacocinética (intensiva)-Día 8, 15 (pre-dosis), 22 de Ciclo 1, Día 8, 15 y 22 de los Ciclos 2-4.
    FC (dispersa)-todas pre-dosis - Día 8, 15, 22 del ciclo 1, Día 8, 15 y 22 de Ciclos 2-4.
    Más detalles disponibles Tabla 4 - Calendario de actividades páginas 43-47 del protocolo
    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 No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1B/2A
    Fase IB/IIA
    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 Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Canada
    France
    Germany
    Italy
    Spain
    United Kingdom
    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
    The End of Trial is defined as either the date of the last visit of the last subject to complete the post-treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date.
    El final del ensayo se define como la fecha de la última visita del último paciente en completar el seguimiento posterior al tratamiento o como la fecha en la que se obtiene del último paciente el último dato necesario para el análisis principal, secundario y/o exploratorio, lo que ocurra más tarde.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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 years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 46
    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 84
    F.4.2.2In the whole clinical trial 106
    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)
    None
    Ninguno
    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 Decision2016-09-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-14
    P. End of Trial
    P.End of Trial StatusOngoing
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