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    Summary
    EudraCT Number:2012-001421-27
    Sponsor's Protocol Code Number:CA180-406
    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:2013-07-12
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2012-001421-27
    A.3Full title of the trial
    Open-Label Single Arm Phase 2 Study Evaluating Dasatinib Therapy Discontinuation In Patients With Chronic Phase Chronic Myeloid Leukemia (CP-CML) With Stable Complete Molecular Response (CMR) DASFREE
    Ensayo en fase II sin enmascaramiento, con un solo grupo, para evaluar la interrupción del tratamiento con dasatinib en pacientes con leucemia mieloide crónica en fase crónica (LMC-FC) con respuesta molecular completa (RMC) estable DASFREE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II study to investigate the effect of discontinuation of Dasatinib treatment in CP-CML patients with stable CMR.
    Estudio de fase II para investigar los efectos de la discontinuación del tratamiento con Dasatinib en pacientes LMC-FC con RMC estable.
    A.4.1Sponsor's protocol code numberCA180-406
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation PlanP/204/2012
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBristol-Myers Squibb International Corporation
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBristol-Myers Squibb International Corporation
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointEU Start Up Department
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance, Avenue de Finlande, 8
    B.5.3.2Town/ cityBraine l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.6E-mailclinical.trials@bms.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Sprycel 20 mg
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/339
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.2Current sponsor codeBMS-354825
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 Sprycel 50 mg
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/339
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.2Current sponsor codeBMS-354825
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Sprycel 80 mg
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/339
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.2Current sponsor codeBMS-354825
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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 Sprycel 100 mg
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/339
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.2Current sponsor codeBMS-354825
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 Sprycel 140 mg
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/339
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.2Current sponsor codeBMS-354825
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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
    Patients with Chronic Phase Chronic Myeloid Leukemia (CP-CML) with stable Complete Molecular Response (CMR) who have received dasatinib as first or second-line treatment for a minimum of 2 years at the time of enrollment and have confirmed dasatinib induced complete molecular remission
    Pacientes con leucemia mieloide crónica en fase crónica (LMC-FC) con respuesta molecular completa (RMC) estable que en el momento del reclutamiento llevan recibiendo dasatinib como tratamiento de primera o segunda línea durante un mínimo de 2 años y con remisión molecular completa confirmada inducida por dasatinib.
    E.1.1.1Medical condition in easily understood language
    Patients affected by Chronic Phase Chronic Myeloid Leukemia treated by dasatinib and with stable complete molecular response
    Pacientes con leucemia mieloide crónica en fase crónica tratados con dasatinib y con respuesta molecular completa estable.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level LLT
    E.1.2Classification code 10054352
    E.1.2Term Chronic phase chronic myeloid leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to assess the rate of major molecular response (MMR), defined as BCR-ABL transcripts <0.1% on International Scale (IS) at 12 months after dasatinib discontinuation in patients who have maintained MMR without re-starting dasatinib treatment
    el objetivo principal de este ensayo es evaluar la tasa de respuesta molecular mayor (RMM), que se define como transcritos de BCR-ABL < 0,1 % en la escala internacional (EI) a los 12 meses de la interrupción de dasatinib en pacientes que han mantenido la RMM sin reiniciar el tratamiento con dasatinib.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study include assessment of the following:
    - event-free survival (EFS) (defined as no molecular relapse including no loss of MMR) at 12 months after dasatinib discontinuation;
    - relapse-free survival (RFS) at 6, 18, 24 months and every 6 months thereafter;
    - BCR-ABL kinetics in those patients who experience intermittent loss of CMR (MR4.5) but no loss of MMR (ie, BCR-ABL blips);
    - assessment of BCR-ABL kinetics in patients who are in CMR (MR4.5) or less when transcript levels are still measurable;
    - rate of transformation to accelerated phase/blast crisis (AP/BC);
    - overall survival
    Los objetivos secundarios de este ensayo incluyen la evaluación de los siguientes parámetros:
    - la supervivencia sin acontecimientos (SSA) (definida como la ausencia de recaída molecular y sin pérdida de RMM) a los 12 meses de la interrupción de dasatinib;
    - la supervivencia sin recaídas (SSR) a los 6, 18, 24 meses y cada 6 meses a partir de entonces;
    - la cinética de BCR-ABL en aquellos pacientes que experimentan pérdida intermitente de la RMC (RM4,5) sin pérdida, no obstante, de RMM (es decir, elevaciones transitorias de BCR-ABL);
    - evaluación de la cinética de BCR-ABL en los pacientes en RMC (RM4,5) o menor cuando los niveles de transcritos son todavía medibles;
    - tasa de transformación a fase acelerada/crisis hemoblástica (FA/CH);
    - la supervivencia global.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Signed Written Informed Consent
    - Patients diagnosed with CP-CML, on treatment with dasatinib for a minimum of 2 years at the time of enrollment and in dasatinib-induced complete molecular remission (CMR defined as ? 0.0032% or 4.5 log reduction of BCR-ABL transcript as determined by local standards) ongoing for at least 1 year prior to study entry
    - Patients are eligible for the screening assessment from the central lab if they have been in stable dasatinib induced CMR for a minimum of nine months, documented by at least three assessments, conducted 2.5 - 3.5 months apart, at a local lab. The first screening assessment conducted at the central lab will be repeated after three months, if the first assessment confirms CMR (MR 4.5). Patients are eligible for enrollment if both assessments from the central lab confirm MR4.5
    - Patients with CP CML treated with dasatinib as first line treatment or second-line treatment after a TKI-based therapy
    - Eligible patients must have achieved a 1-log reduction in BCR-ABL transcript levels compared to baseline as determined by local standards or less than or equal to 10% IS at 3 months for current dasatinib therapy (first or second line)
    - ECOG PS of 0-1
    - Life expectancy of > 1 year
    - Adequate renal function defined as serum creatinine ? 3.0 times the institutional ULN
    - Adequate hepatic function defined as: total bilirubin ? 2.0 times the institutional ULN;alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? 2.5 times the institutional upper limit of normal (ULN)
    - Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal. Patients with low K, Mg levels, total serum Ca and/or ionized Ca must be replete to allow for protocol entry
    - Subject Re-enrollment: This study does not permit the re-enrollment of a subject that has discontinued the study as a pre-treatment failure
    - Men and women, ages 18 or older years, inclusive
    - Women of childbearing potential (WOCBP) must use method(s) of contraception throughout the entire study period (i.e., during the study periods of dasatnib discontinuation and during re-initiation of dasatinib)
    - Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to study entry, at each study visit, and 72 hours prior to re-initiation of dasatinib
    - Women must not be breastfeeding
    - Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year
    - Women who are not of childbearing potential (i.e,, who are postmenopausal or surgically sterile) and azoospermic men do not
    require contraception
    - Firma de Consentimiento Informado por escrito.
    - pacientes diagnosticados con LMC-FC, en tratamiento con dasatinib un mínimo de 2 años en el reclutamiento, y con remisión molecular completa inducida por dasatinib (donde la RMC se define como una reducción ? 0,0032 % o de log 4,5 de los transcritos de BCR-ABL según lo determinado por las normas locales) continua de al menos 1 año antes de su inclusión en el ensayo.
    - Los pacientes son elegibles para la evaluación de preselección por parte del laboratorio central si presentan una RMC inducida por dasatinib estable de una duración mínima de 9 meses, documentada por al menos 3 evaluaciones separadas por intervalos de entre 2,5 y 3,5 meses y realizadas en un laboratorio local. Si la primera evaluación confirma la RMC (RM4,5), la primera evaluación de preselección realizada en el laboratorio central se repetirá a los tres meses. Los pacientes son elegibles para ser reclutados si ambas evaluaciones del laboratorio central confirman la RM.
    - Pacientes con LMC-FC tratados con dasatinib como tratamiento de primera línea, o pacientes tratados con ITC como tratamiento de primera línea y que están recibiendo dasatinib como tratamiento de segunda línea.
    - Los pacientes elegibles deben haber logrado una reducción de log 1 en los niveles de transcritos de BCR-ABL en comparación con el valor inicial, determinado por las normas locales, o menor o igual al 10 % en la EI (escala internacional) a los 3 meses del tratamiento actual con dasatinib (primera o segunda línea).
    - Categoría funcional ECOG de 0-1
    - Esperanza de vida > 1 año
    - Función renal adecuada, definida como creatinina sérica ? 3 veces el LSN establecido
    - Función hepática adecuada, definida como bilirrubina ? 2 veces el LSN total establecido; alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST) ? 2,5 veces el LSN establecido.
    - Las concentraciones séricas de Na, K, Mg, y la concentración sérica total de Ca o los niveles de Ca ionizado deben ser superiores o iguales al límite inferior de las concentraciones normales establecidas. Si el paciente presenta niveles bajos de K, Mg, Ca total en suero o Ca ionizado, no podrá ingresar en el protocolo hasta que dichos niveles se hayan corregido.
    - Reinscripción de pacientes: en este ensayo no se permite la reinscripción de aquellos pacientes que hayan tenido que abandonar el ensayo como fracasos del tratamiento anterior.
    - Hombres y mujeres a partir de los 18 años.
    - Las mujeres en edad fértil deben utilizar métodos anticonceptivos durante todo el ensayo (es decir, tanto durante los períodos de interrupción de la administración de dasatinib como durante su reinicio).
    - Las mujeres deben obtener resultados negativos en las pruebas de embarazo en suero u orina (sensibilidad mínima de 25 UI/l o unidades equivalentes de hCG) realizadas como máximo 72 horas antes de su incorporación al ensayo, en cada visita del ensayo y 72 horas antes de la reiniciación de la administración de dasatinib.
    - Las mujeres no deben hallarse en período de lactancia.
    - Los hombres que mantienen relaciones sexuales con MEF deben usar un método anticonceptivo con una tasa de fracaso inferior al 1 % al año.
    - Las mujeres que no están en edad fértil (es decir, que son posmenopáusicas o quirúrgicamente estériles ?consulte la definición de MEF en el Apartado 3.3.3?) y los hombres con azoospermia no necesitan utilizar métodos anticonceptivos.
    E.4Principal exclusion criteria
    - Subjects with more than one CML treatment before dasatinib
    - Lack of a 1-log reduction in BCR-ABL transcript levels compared to baseline as determined by local standards or > 10% IS at 3 months since beginning dasatinib therapy (first or second line).
    - Patients who have previously undergone hematopoietic stem cell transplantation (SCT) or who are scheduled for SCT
    - Any prior treatment with interferon
    - Previous diagnosis of CML accelerated phase or blast crisis
    - Prior or concurrent malignancy, except the following:
    i) Curatively treated basal cell or squamous cell skin cancer
    ii) Cervical carcinoma in situ
    iii) Adequately treated Stage I or II cancer from which the subject is currently in complete remission
    iv) Any other cancer from which the subject has been disease free for 3 years
    - A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
    - Uncontrolled or significant cardiovascular disease, including any of the following:
    i. Congestive cardiac failure (NYHA > 2) within 3 months
    ii. Diagnosed or suspected congenital long QT syndrome
    iii. Any history of clinically significant ventricular arrhythmias
    iv. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
    v. Any history of second- or third-degree heart block (may be eligible if the subject
    currently has a pacemaker)
    vi. Uncontrolled angina within 3 months
    vii. Prior myocardial infarction within 6 months
    viii. Uncontrolled hypertension
    - Pulmonary arterial hypertension
    - Subjects with pericardial effusion of any grade at study entry are excluded. Subjects previously diagnosed with pleural/pericardial effusion of any grade resolved at the time of study entry are allowed
    - History of significant bleeding disorder unrelated to CML, including
    i. Diagnosed congenital bleeding disorders (e.g., von Willebrand?s disease)
    ii. Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
    - Physical and Laboratory Test Findings
    - Subjects with known hypersensitivity to excipients of dasatinib tablets (Tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium; hydroxypropyl cellulose, magnesium stearate; Film-coating: hypromellose titanium dioxide macrogol 400)
    - Patients with a history of non-compliance to CML treatment and monitoring requirements
    - Patients who are pregnant or breastfeeding or likely to become pregnant
    - Men whose partner is unwilling or unable to avoid pregnancy
    - Prisoners or subjects who are involuntarily incarcerated
    - Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
    - Pacientes que han recibido más de un tratamiento para la LMC antes del dasatinib.
    - Ausencia de reducción de log 1 en los niveles de transcritos de BCR-ABL en comparación con el valor inicial, determinado por las normas locales, o superior o igual al 10 % en la escala internacional a los 3 meses desde el inicio del tratamiento con dasatinib (primera o segunda línea).
    - Pacientes que sometidos previamente a trasplante de células precursoras (TCP) hematopoyéticas o que tengan un TCP programado.
    - Cualquier tratamiento previo con interferón.
    - Diagnóstico previo de fase acelerada o crisis hemoblástica de la LMC.
    - Enfermedad cancerosa anterior o concomitante, excepto las siguientes:
    i) Carcinoma basocelular o espinocelular en tratamiento curativo
    ii)Carcinoma cervicouterino localizado
    iii)Cáncer en estadio I o II tratado adecuadamente, del cual el paciente se halla actualmente en remisión completa
    iv)Cualquier otro tipo de cáncer del cual el paciente esté curado desde hace 3 años
    - Cualquier trastorno médico grave no controlado o infección activa que pueda afectar la capacidad del paciente para recibir el tratamiento del protocolo
    - Cualquier enfermedad cardiovascular significativa o no controlada, incluidas las siguientes:
    i.Insuficiencia cardíaca congestiva (NYHA > 2) en los 3 últimos meses
    ii.Diagnóstico o sospecha de síndrome de QT largo congénito
    iii.Cualquier antecedente de arritmias ventriculares clínicamente significativas
    iv.Intervalo QTc prolongado en el electrocardiograma realizado antes de la inscripción (> 450 ms)
    v.Antecedentes de bloqueo auriculoventricular de segundo o tercer grado (el paciente puede ser elegible si actualmente lleva un marcapasos)
    vi.Angina de pecho no controlada durante los últimos 3 meses
    vii.Infarto de miocardio anterior durante los últimos 6 meses
    Viii. Hipertensión no controlada
    - Hipertensión arterial pulmonar
    - Pacientes con derrame pericárdico de cualquier grado al inicio del estudio están excluidos. Los pacientes con un diagnóstico previo de derrame pleural/pericárdico de cualquier grado resueltos en el momento de la inclusión en el ensayo son elegibles.
    - Antecedentes de trastorno hemorrágico significativo no relacionado con la LMC, incluidos
    i.Trastornos hemorrágicos congénitos diagnosticados (por ejemplo, la enfermedad de von Willebrand)
    ii.Trastorno hemorrágico adquirido diagnosticado durante el año precedente (por ejemplo, anticuerpos antifactor VIII adquiridos)
    - Resultados de los exámenes físicos y las pruebas analíticas
    - Pacientes con hipersensibilidad conocida a los excipientes de los comprimidos de dasatinib (núcleo del comprimido: monohidrato de lactosa, celulosa microcristalina, croscarmelosa sódica, hidroxipropilcelulosa, estearato de magnesio; recubrimiento: hipromelosa dióxido de titanio macrogol 400).
    - Pacientes con antecedentes de incumplimiento con los requisitos de tratamiento y seguimiento de la LMC
    - Pacientes embarazadas o en lactación, o que es probable que se queden embarazadas
    - Hombres cuya pareja no está dispuesta o no puede evitar el embarazo
    - Reclusos o pacientes encarcelados involuntariamente
    - Pacientes internados forzosamente para recibir tratamiento para algún trastorno psiquiátrico o físico (por ejemplo, enfermedades infecciosas)
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint, the MMR rate at 12 months, is the proportion of enrolled subjects who maintain MMR 12 months after dasatinib discontinuation compared with the enrolled
    subjects in the study
    La principal variable de eficacia, la tasa de RMM a los 12 meses, es la proporción de pacientes reclutados que mantienen la RMM 12 meses después de la interrupción de la administración de dasatinib en relación con el total de pacientes reclutados en el ensayo.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months after dasatinib discontinuation
    12 meses tras la discontinuación del dasatinib
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints include:
    - event-free survival at 12 months after dasatinib discontinuation
    - relapse-free survival at 6, 18, 24 months and every 6 months thereafter after dasatinib discontinuation
    - assessment of BCR-ABL kinetics for subjects who experience loss of CMR but not MMR
    - assessment of BCR-ABL kinetics in subjects in CMR with measurable levels
    - the rate of transformation to AP/BC, and overall survival
    Las variables de eficacia secundarias incluyen:
    - la supervivencia sin acontecimientos a los 12 meses de la interrupción de la administración de dasatinib;
    - la supervivencia sin recaídas a los 6, 18, 24 meses y, posteriormente, cada 6 meses después de la interrupción de la administración de dasatinib;
    - la evaluación de la cinética de BCR-ABL para los pacientes que experimentan pérdida de la RMC pero no de la RMM;
    - la evaluación de la cinética de BCR-ABL en pacientes en RMC con niveles mensurables;
    - la tasa de transformación a FA/CH y la supervivencia global.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - event-free survival at 12 months after dasatinib discontinuation
    - relapse-free survival at 6, 18, 24 months and every 6 months thereafter after dasatinib discontinuation
    - supervivencia sin acontecimientos a los 12 meses de la interrupción de la administración de dasatinib;
    - supervivencia sin recaídas a los 6, 18, 24 meses y, posteriormente, cada 6 meses después de la interrupción de la administración de dasatinib;
    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 No
    E.6.4Safety Yes
    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) 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 No
    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) 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    Finland
    France
    Italy
    Spain
    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
    LVLS
    última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months2
    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: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state13
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 75
    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)
    At the end of the study, BMS will not continue to supply study drug to subjects/investigators
    unless BMS chooses to extend the study. The investigator should ensure that the subject receives
    appropriate standard of care to treat the condition under study.
    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 Decision2013-08-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-08-06
    P. End of Trial
    P.End of Trial StatusOngoing
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