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    Summary
    EudraCT Number:2015-004856-24
    Sponsor's Protocol Code Number:AC220-A-U302
    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:2016-06-09
    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 number2015-004856-24
    A.3Full title of the trial
    A Phase 3, Double-Blind, Placebo-controlled Study of Quizartinib (AC220) Administered in Combination with Induction and Consolidation Chemotherapy, and Administered as Maintenance Therapy in Subjects 18 to 75 Years Old with Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (QuANTUM First)
    Estudio de fase III, doble ciego, controlado con placebo de quizartinib (AC220) administrado en combinación con quimioterapia de inducción y consolidación, y administrado como terapia de mantenimiento a sujetos de 18 a 75 años con leucemia mielógena aguda FLT3ITD (+) de nuevo diagnóstico (QuANTUM-First)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Trial Study of Quizartinib (AC220) Administered in Combination with Induction and Consolidation Chemotherapy, and Administered as Maintenance Therapy in Subjects 18 to 75 Years Old with Newly Diagnosed Acute Myeloid Leukemia
    Estudio clínico de quizartinib (AC220) administrado en combinación con quimioterapia de inducción y consolidación, y administrado como terapia de mantenimiento a sujetos de 18 a 75 años con leucemia mielógena aguda de nuevo diagnóstico
    A.4.1Sponsor's protocol code numberAC220-A-U302
    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 SponsorDaiichi Sankyo, 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 supportDaiichi Sankyo Co. Ltd.
    B.4.2CountryJapan
    B.4.1Name of organisation providing supportDaiichi Sankyo Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo, Inc.
    B.5.2Functional name of contact pointJasmina Markov
    B.5.3 Address:
    B.5.3.1Street Address399 Thornall Street
    B.5.3.2Town/ cityEdison, NJ
    B.5.3.3Post code08837
    B.5.3.4CountryUnited States
    B.5.6E-mailjmarkov@dsi.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/09/622
    D.3 Description of the IMP
    D.3.1Product nameQuizartinib 20mg
    D.3.2Product code AC220
    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 INNQuizartinib dihydrochloride
    D.3.9.1CAS number 1132827-21-4
    D.3.9.2Current sponsor codeAC220
    D.3.9.3Other descriptive nameQUIZARTINIB
    D.3.9.4EV Substance CodeSUB89721
    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 No
    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/3/09/622
    D.3 Description of the IMP
    D.3.1Product nameQuizartinib 30mg
    D.3.2Product code AC220
    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 INNQuizartinib dihydrochloride
    D.3.9.1CAS number 1132827-21-4
    D.3.9.2Current sponsor codeAC220
    D.3.9.3Other descriptive nameQUIZARTINIB
    D.3.9.4EV Substance CodeSUB89721
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (+) acute myeloid leukemia (AML)
    Leucemia mielógena aguda (LMA) con duplicación interna en tándem (ITD) (+) de la tirosincinasa 3 similar a FMS (FLT3) de nuevo diagnóstico
    E.1.1.1Medical condition in easily understood language
    Acute Myeloid Leukemia (AML) a cancer of the blood.
    Leucemia mielógena aguda (LMA) un cáncer de la sangre.
    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 10000886
    E.1.2Term Acute myeloid leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to compare the effect of quizartinib vs placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 12 cycles) on event-free survival (EFS) in subjects with newly diagnosed FLT3-ITD (+) AML.
    El objetivo principal consiste en comparar el efecto de quizartinib frente a placebo (administrado con quimioterapia de inducción y consolidación estándar, y después administrado como terapia de mantenimiento durante un máximo de 12 ciclos) sobre la supervivencia sin complicaciones (SSC) en sujetos con LMA FLT3-ITD (+) de nuevo diagnóstico.
    E.2.2Secondary objectives of the trial
    To compare the following in subjects treated with quizartinib vs placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 12 cycles):
    - Overall survival (OS);
    - Complete remission (CR) rate;
    - Composite complete remission rate (CRc = CR + CRp [Complete Remission with Incomplete Platelet Recovery] + CRi [Complete Remission with Incomplete Neutrophil Recovery]);
    - Percentage of subjects achieving CR with no evidence of Minimal Residual Disease (MRD) following induction therapy.

    Other Secondary Objectives:
    To further characterize the safety profile of quizartinib administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 12 cycles.
    To assess the pharmacokinetics (PK) of quizartinib and its metabolite (AC886).
    Comparar lo siguiente en sujetos tratados con quizartinib
    frente a placebo (administrado con quimioterapia de inducción y consolidación estándar, y después administrado como terapia de mantenimiento durante un máximo de 12 ciclos):
    - La supervivencia global (SG);
    - Tasa de remisión completa (RC);
    - Tasa de remisión completa combinada (RCc =RC + RC con recuperación de trombocitos incompleta [RCp] + RC con recuperación incompleta de neutrófilos [RCi]);
    - Porcentaje de sujetos que logran la RC sin evidencia de enfermedad residual mínima (ERM) después de la terapia de inducción.

    Otros objetivos secundarios:

    Caracterizar aún más el perfil de seguridad del quizartinib administrado con quimioterapia de inducción y consolidación estándar, y después administrado como terapia de mantenimiento durante un máximo de 12 ciclos.

    Evaluar la farmacocinética (FC) del quizartinib y su metabolito (AC886).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Up to 100 subjects will have intense pharmacokinetic (PK) sampling for plasma quizartinib (AC220) concentrations and its metabolite (AC886) at Cycle 1 during the Induction phase on Day 8, Day 15, and Day 21, within 10 minutes after the ECG is performed. This will be referred as the PK-ECG-Biomarker Substudy.
    Un máximo de 100 sujetos se someterán a un muestreo intenso para el análisis FC destinado a determinar las concentraciones plasmáticas de quizartinib (AC220) y su metabolito (AC886) el día 8, el día 15 y el día 21 del ciclo 1 de la fase de inducción,, 10 minutos después de la realización del ECG. Esto se denomina Subestudio de FC-ECG-Biomarcadores, para el subestudio opcional de biomarcadores-FC-ECG: Véase protocolo sección 8.1.2 y 8.2 del Protocolo.
    E.3Principal inclusion criteria
    1. Must be competent and able to comprehend, sign, and date an Ethics Committee or Institutional Review Board approved Informed Consent Form (ICF) before performance of any study-specific procedures or tests;
    2. >=18 years or the minimum legal adult age (whichever is gre
    ater) and z<=75 years (at Screening);

    3. Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome, based on the World Health Organization (WHO) 2008 classification (at Screening);

    4. Eastern Cooperative Oncology Group performance status 0-2 (at Screening);

    5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of >=3% FLT3-ITD/total FLT3);

    6. Subject is receiving standard 7+3 induction chemotherapy regimen as specified in the protocol;

    7. Adequate renal function defined as:
    a. Serum creatinine <=1.5 × the upper limit of normal (ULN); or
    b. Glomerular filtration rate >50 mL/min/1.73m2, as calculated with the modified Cockcroft Gault equation;

    8. Adequate hepatic function defined as:
    a.Total serum bilirubin <=1.5 × ULN;
    b.Serum alkaline phosphatase, aspartate transaminase and alanine transaminase <=2.5 × ULN;

    9. Serum electrolytes (potassium, calcium, and magnesium) within normal limits. If outside of normal limits, subject will be eligible when electrolytes are corrected;

    10. If female, must be either postmenopausal (no menstrual period for a minimum of 12 months), surgically sterile, or if of childbearing potential, must have a negative serum pregnancy test upon entry into this study and must be willing to use maximally effective double-barrier birth control during the period of therapy and contraception for 3 months following the last investigational drug dose;

    11. If male, must be surgically sterile or willing to use an effective double-barrier contraception method upon enrollment, during the course of the study, and for 3 months following the last investigational drug dose.
    1.Deben ser jurídicamente competentes y ser capaces de entender, firmar y fechar un formulario de consentimiento informado (FCI) aprobado por el Comité de ética de investigación clínica antes de que se realice cualquier prueba o procedimiento específico del estudio

    2. >=18 años de edad o la mayoría de edad mínima (la que sea mayor) y <=75 años (en la visita de selección)

    3. LMA primaria morfológicamente documentada o LMA secundaria a síndrome mielodisplásico recién diagnosticada, con arreglo a la clasificación de la Organización Mundial de la Salud (OMS) 2008 (en la visita de selección)

    4. Estado funcional del Grupo Oncológico Cooperativo de la Costa Este (ECOG) 0-2 (en la visita de selección)

    5. Presencia de mutación activadora en FLT3-ITD en la médula ósea (índice alélico de >=3 % FLT3- ITD/FLT3 total)

    6. El sujeto está recibiendo una quimioterapia de inducción 7+3 estándar según lo previsto en el protocolo

    7. Actividad renal adecuada definida como:

    a. Creatinina sérica <= 1,5 veces el límite superior de la normalidad (LSN); o
    b. Tasa de filtración glomerular >50 ml/min/1,73m2, calculada por medio de la ecuación de Cockcroft Gault modificada;

    8. Actividad hepática adecuada definida como:
    a. Bilirrubina sérica total <=1,5 veces LSN
    b. Fosfatasa alcalina sérica, aspartato aminotransferasa y alanina aminotransferasa <=2,5 veces el LSN

    9. Electrolitos séricos (potasio, calcio y magnesio) dentro de los límites normales. Si los electrolitos se encuentran fuera de los límites normales, el sujeto será elegible cuando vuelvan al intervalo normal

    10. Si es mujer, debe ser postmenopáusica (sin período menstrual durante un mínimo de 12 meses) o haber sido esterilizada quirúrgicamente; si tiene posibilidad de quedar embarazada, debe tener un resultado negativo en una prueba de embarazo en sangre realizada al entrar en este estudio y comprometerse a utilizar un método anticonceptivo de doble barrera eficaz en grado máximo durante el período de la terapia y durante los tres meses posteriores a la administración de la última dosis del fármaco en fase de investigación;

    11. Si es un hombre, debe haber sido esterilizado quirúrgicamente o comprometerse a utilizar un método anticonceptivo de doble barrera eficaz en grado máximo durante el período de la terapia y durante los tres meses posteriores a la administración de la última dosis del fármaco en fase de investigación;
    E.4Principal exclusion criteria
    1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or BCR-ABL positive leukemia (ie, chronic myelogenous leukemia in blast crisis);

    2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;

    3. Prior treatment for AML, except for the following allowances:
    a. Leukapheresis;
    b. Treatment for hyperleukocytosis with hydroxyurea;
    c. Cranial radiotherapy for central nervous system (CNS) leukostasis;
    d. Prophylactic intrathecal chemotherapy;
    e. Growth factor/cytokine support;

    4. Prior treatment with quizartinib or other FLT3-ITD inhibitors;

    5. Prior treatment with any investigational drug or device within 30 days prior to Randomization or who are currently participating in other investigational procedures;

    6. History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for subjects with symptoms of CNS leukemia to rule out extramedullary CNS involvement;

    7. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for at least 2 years;

    8. Uncontrolled or significant cardiovascular disease, including any of the following:
    a. Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;
    b. QTcF interval >450 msec;
    c. Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);
    d. Systolic blood pressure >=180 mmHg or diastolic blood pressure >=110 mmHg;
    e. History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
    f. History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
    g. History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;
    h. History of New York Heart Association Class 3 or 4 heart failure;
    i. Known history of left ventricular ejection fraction (LVEF) <=45% or less than the institutional lower limit of normal;
    j. History of complete left or complete right bundle branch block;

    9. Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;

    10. Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C)

    11. Known history of human immunodeficiency virus (HIV). Subjects should be tested for HIV prior to randomization if required by local regulations or EC;

    12. History of hypersensitivity to any excipients in the quizartinib/placebo tablets;

    13. Females who are pregnant or breastfeeding;

    14. Otherwise considered inappropriate for the study by the investigator.
    1. Diagnóstico de leucemia promielocítica aguda (LPA), clasificación francesa-estadounidense- británica M3 o clasificación LPA de la OMS con translocación, t(15;17)(q22;q12), o leucemia positiva BCR-ABL (es decir, leucemia mielógena crónica en crisis blástica)

    2. Diagnóstico de LMA secundaria a quimioterapia o radioterapia anterior para otras neoplasias

    3. Tratamiento anterior para la LMA, excepto en los siguientes casos:
    4. Leucocitaféresis;
    5. Tratamiento de hiperleucocitosis con hidroxiurea
    6. Radioterapia craneal para leucostasis del sistema nervioso central (SNC)
    7. Quimioterapia intratecal profiláctica
    8. Soporte con citocinas / factor de crecimiento

    9. Tratamiento anterior con quizartinib u otros inhibidores del FLT3-ITD

    10. Tratamiento anterior con un fármaco o dispositivo experimental en los 30 días anteriores a la aleatorización o que se encuentran participando en otros procedimientos experimentales

    11. Antecedentes de leucemia del SNC confirmada, con líquido cefalorraquídeo positivo para blastos de la LMA; se recomienda punción lumbar para sujetos con síntomas de leucemia del SNC con el fin de descartar afectación extramedular del SNC

    12. Antecedentes de otras neoplasias malignas, salvo cáncer de piel no melanocítico, carcinoma in-situ tratado curativamente, u otros tumores sólidos tratados curativamente sin evidencia de enfermedad durante al menos 2 años

    13. Enfermedad cardiovascular importante o mal controlada, incluidas cualquiera de las siguientes:

    a. Bradicardia de menos de 50 latidos por minuto, salvo que el sujeto tenga un marcapasos
    b. Intervalo QTcF >450 ms
    c. Diagnóstico o sospecha de síndrome de QT largo (incluidos antecedentes familiares de síndrome de QT largo)
    d. Presión arterial máxima >= 180 mmHg o presión arterial mínima >= 110 mmHg
    e. Antecedentes de arritmias ventriculares clínicamente relevantes (p. ej. taquicardia ventricular, fibrilación ventricular o Torsade de Pointes);
    f. Antecedentes de bloqueo auriculoventricular de segundo (Mobitz II) o tercer grado (los sujetos con marcapasos son elegibles si no tienen antecedentes de síncope o de arritmias clínicamente relevantes durante el uso del marcapasos)
    14. Antecedentes de infarto de miocardio o angina de pecho mal controlada en los 6 meses anteriores a la visita de selección
    15. Antecedentes de insuficiencia cardíaca de clase 3 o 4 según la clasificación de la New York Heart Association
    16. Antecedentes confirmados de fracción de eyección del ventrículo izquierdo (FEVI) <= 45 % o menor al límite inferior de la normalidad institucional
    17. Antecedentes de bloqueo completo de la rama izquierda o derecha del haz de His

    18. Infección vírica, bacteriana o fúngica sistémica aguda o crónica activa mal controlada con terapia antivírica, antibacteriana o antifúngica

    19. Hepatopatía activa confirmada clínicamente relevante (p. ej. hepatitis B activa o hepatitis C activa)

    20. Antecedentes confirmados de infección por virus de la inmunodeficiencia humana (VIH). Los sujetos deben someterse a una prueba de detección del VIH antes de la aleatorización si así lo exige la normativa local o el CEI

    21. Antecedentes de hipersensibilidad a cualquiera de los excipientes de los comprimidos de quizartinib/placebo

    22. Mujeres en período de embarazo o lactancia

    23. Cualquier otra persona que el investigador considere inadecuada para participar en el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is Event Free Survival in the Intent-to treat (ITT) Analysis Set.
    El criterio de valoración principal de la eficacia es la SSC en el grupo de análisis por intención de tratar (IDT).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Date of earliest of any of the following:

    - Refractory disease (or treatment failure) which is determined at the end of the Induction Phase;
    - Relapse after CR, CRp or CRi;
    - Death from any cause at any time during the study.
    Tiempo transcurrido entre la aleatorización y la fecha de presentación del primero de los siguientes acontecimientos:

    - Enfermedad resistente (o fracaso del tratamiento) determinada al final de la fase de inducción

    - Recidiva después de RC, RCp o RCi,

    - Muerte por cualquier causa y en cualquier momento durante el estudio.
    E.5.2Secondary end point(s)
    1. Overall survival, defined as the time from randomization until death from any cause;
    2. Complete remission rate which is the percent of subjects achieving CR after Induction;
    3. Composite complete remission rate, which is the percent of subjects achieving CRc after induction;
    4. Percent of subjects achieving CR with no evidence of MRD following induction therapy. Minimal residual disease is defined as the presence of leukemic cells in the bone marrow detected above a predefined cut off level by a validated assay in subjects who meet the standard requirements for a CR.
    - Supervivencia global definida como el tiempo transcurrido entre la aleatorización y la muerte por cualquier causa

    - Tasa de remisión completa, que es el porcentaje de sujetos que logran la RC después de la fase de inducción

    - Tasa de remisión completa combinada, que es el porcentaje de sujetos que logran la RCc después de la fase de inducción

    - Porcentaje de sujetos que logran la RC sin evidencia de ERM después de la terapia de inducción. Enfermedad residual mínima se define como la presencia de células leucémicas en la médula ósea detectadas por encima de un nivel de corte predeterminado en un ensayo validado en sujeto que cumple los requisitos estándar para una RC.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Lost to follow-up
    2. Outcome at the end of induction cycle 1 and the induction phase
    3. Same as point 2
    4. Same as point 2
    1. Perdida de seguimiento
    2, 3 y 4: Resultado al final del ciclo 1 de inducción y al final de la fase de inducción
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned26
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA135
    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
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The study will continue until the target number of EFS events is achieved and at least 14 months have elapsed since completion of enrollment; the end of the trial will be the date of the last subject visit.
    El estudio seguirá hasta alcanzar un número específico de acontecimientos de SSC y hasta después de transcurridos como mínimo 14 meses tras la conclusión del reclutamiento; el final del ensayo será la fecha de la visita del último sujeto.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 years4
    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: 268
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 268
    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 state69
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 536
    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)
    An end of treatment visit (+7 days) is scheduled, followed by a 30 day (+7 days) safety follow-up visit, and then long-term visits will be performed as follows:

    - every 4 weeks for subjects who have NOT had an EFS event
    - every 12 weeks for subjects who have had an EFS event

    All subjects will be followed for survival and subsequent anti-cancer therapy, if available.
    Se fija visita fin de tratamiento ( + 7 dias), seguida de visita deseguimiento de seguridad a los 30 días, y comenzarán las visitas de seguimiento a largo plazo, como sigue:
    - cada 4 semanas para sujetos que no registraron un acontecimiento de SSC;
    - cada 12 semanas para sujetos que registraron un acontecimiento de SSC;
    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 Decision2016-07-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-04
    P. End of Trial
    P.End of Trial StatusOngoing
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