Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38177   clinical trials with a EudraCT protocol, of which   6271   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-001466-28
    Sponsor's Protocol Code Number:M15-656
    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:2017-08-10
    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 number2016-001466-28
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of Venetoclax in Combination with Azacitidine Versus Azacitidine in Treatment Naïve Subjects with Acute Myeloid Leukemia who are Ineligible for Standard Induction Therapy
    Estudio aleatorizado, doble ciego, controlado con placebo, Fase 3, de Venetoclax en combinación con Azacitidina en comparación con Azacitidina, en pacientes con leucemia mieloide aguda no tratados anteriormente y no elegibles para terapias de inducción estándar.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Venetoclax in Combination with Azacitidine Versus Azacitidine in previously untreated Subjects with Acute Myeloid Leukemia who are Ineligible for Standard Induction Therapy
    Estudio de Venetoclax en combinación con Azacitidina en comparación con Azacitidina, en pacientes con leucemia mieloide aguda no tratados anteriormente y no elegibles para terapias de inducción estándar
    A.4.1Sponsor's protocol code numberM15-656
    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 SponsorAbbVie Deutschland GmbH & Co. KG
    B.1.3.4CountryGermany
    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 supportAbbVie Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAbbVie Ltd.
    B.5.2Functional name of contact pointEU Clinical Trials Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressAbbVie House, Vanwall Business Park, Vanwall Road
    B.5.3.2Town/ cityMaidenhead, Berkshire
    B.5.3.3Post codeSL6 4UB
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+34901200103
    B.5.6E-mailabbvie_reec@abbvie.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 nameVenetoclax
    D.3.2Product code ABT-199 (GDC-0199)
    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 INNVenetoclax
    D.3.9.2Current sponsor codeABT-199 (GDC-0199)
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 nameVenetoclax
    D.3.2Product code ABT-199 (GDC-0199)
    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 INNVenetoclax
    D.3.9.2Current sponsor codeABT-199 (GDC-0199)
    D.3.9.4EV Substance CodeSUB176260
    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 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 nameVenetoclax
    D.3.2Product code ABT-199 (GDC-0199)
    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 INNVenetoclax
    D.3.9.2Current sponsor codeABT-199 (GDC-0199)
    D.3.9.4EV Substance CodeSUB176260
    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.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
    D.8 Placebo: 2
    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
    D.8 Placebo: 3
    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
    Acute Myeloid Leukemia
    Leucemia mieloide aguda
    E.1.1.1Medical condition in easily understood language
    Cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.
    Cáncer línea mieloide de las células sanguíneas, caract por el ráp crecimiento de glóbulos blancos anormales que se acumulan en la médula ósea e interfieren con la producc de célu sanguíneas normles.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10000886
    E.1.2Term Acute myeloid leukemia
    E.1.2System Organ Class 100000012984
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate if venetoclax in combination with azacitidine will improve overall survival (OS) and composite complete remission rate (complete remission + complete remission with incomplete marrow recovery; CR/CRi) versus placebo in combination with azacitidine, in treatment naïve subjects with acute myeloid leukemia (AML).
    Determinar si venetoclax combinado con azacitidina mejora la supervivencia global (SG) y la tasa de remisión completa compuesta (remisión completa + remisión completa con recuperación incompleta de la médula; RC/RCi), en comparación con un placebo combinado con azacitidina, en el tratamiento de pacientes con leucemia mieloide aguda (LMA) no tratados previamente.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are:
    • To evaluate if venetoclax in combination with azacitidine will improve, event-free survival (EFS).
    • To evaluate if venetoclax in combination with azacitidine will improve the proportion of subjects achieving composite complete remission (CR or CRi) by the initiation of Cycle 2.
    • To evaluate if venetoclax in combination with azacitidine reduces fatigue and improves global health status/quality of life (GHS/QoL) based on patient reported outcome (PRO) assessments (Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] 7a and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core [EORTC QLQ-C30]).
    • Determinar si venetoclax en combinación con azacitidina mejora la supervivencia sin episodios (SSE)
    • Determinar si venetoclax en combinación con azacitidina mejora la proporción de sujetos que logran remisión completa compuesta (RC o RCi) por el inicio del ciclo 2.
    • Determinar si venetoclax en combinación con azacitidina disminuye el cansancio y mejora el estado general de salud/calidad de vida (EGS/CdV) según las evaluaciones de los resultados comunicados por los pacientes (RCP) (Cuestionario breve del cansancio en el cáncer [SF] 7a del Patient Reported Outcomes Measurement Information System [PROMIS] y Cuestionario esencial de calidad de vida de la European Organization for Research and Treatment of Cancer [EORTC QLQ-C30]).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A subject will be eligible for study participation if he/she meets the following criteria within 21 days prior to randomization.
    ● Subject must have confirmation of AML by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.
    ● Subject must be ≥ 18 years of age.
    ● Subject must have a projected life expectancy of at least 12 weeks.
    ● Subject must be considered ineligible for induction therapy defined by the following:
    - ≥ 75 years of age; OR
    - ≥ 18 to 74 years of age with at least one of the following co-morbidities:
    ○ ECOG Performance Status of 2 or 3;
    ○ Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina;
    ○ DLCO ≤ 65% or FEV1 ≤ 65%;
    ○ Creatinine clearance ≥ 30 mL/min to < 45 ml/min;
    ○ Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN;
    ○ Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the AbbVie TA MD before study enrollment.
    ● Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status:
    - 0 to 2 for subjects ≥ 75 years of age OR
    - 0 to 3 for subjects ≥ 18 to 74 years of age.
    ● Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.
    ● Subject must have adequate liver function as demonstrated by:
    - aspartate aminotransferase (AST) ≤ 3.0 × ULN*
    - alanine aminotransferase (ALT) ≤ 3.0 × ULN*
    - bilirubin ≤ 1.5 × ULN*
    * Unless considered to be due to leukemic organ involvement
    o Subjects who are < 75 years of age may have a bilirubin of ≤ 3.0 × ULN
    ● Female subjects must be either postmenopausal defined as:
    - Age > 55 years with no menses for 12 or more months without an alternative medical cause
    - Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level > 40 IU/L.
    OR
    - Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
    OR
    - Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.
    ● Male subjects who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.
    ● Female subjects of childbearing potential must have negative results for pregnancy test performed:
    - At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
    - Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.
    ● Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
    Para poder participar en el estudio, los pacientes deben cumplir los criterios siguientes en los 21 días previos a la aleatorización.
    1. El paciente debe presentar LMA confirmada según los criterios de la OMS y no ser apto para recibir tratamiento con una pauta de inducción convencional con citarabina y antraciclina debido a la edad o a la presencia de enfermedades concomitantes.
    2. El paciente debe tener ≥ 18 años de edad.
    3. El paciente debe tener una esperanza de vida prevista de 12 semanas como mínimo.
    4. El paciente no debe ser apto para tratamiento de inducción, lo que se define por lo siguiente:
    • ≥ 75 años de edad;
    O
    • ≥ 18 a 74 años de edad con al menos una de las enfermedades concomitantes siguientes:
    o Estado funcional conforme del ECOG de 2 o 3;
    o Antecedentes de ICC con necesidad de tratamiento o fracción de eyección ≤ 50% o angina estable crónica;
    o DLCO ≤ 65% o FEV1 ≤ 65%;
    o Aclaramiento de creatinina ≥ 30 ml/min a < 45 ml/min
    o Insuficiencia hepática moderada con bilirrubina total > 1,5 a ≤ 3,0 × LSN
    o El AT MD de AbbVie debe revisar y aprobar cualquier otra enfermedad concomitante que el médico considere incompatible con la quimioterapia intensiva antes de la inscripción en el estudio
    5. El paciente debe presentar un estado funcional del Eastern Cooperative Oncology Group (ECOG):
    • de 0 a 2 si tienen ≥ 75 años.
    O
    • de 0 a 3 si tiene ≥ 18 a 74 años.
    6. El paciente debe tener una función renal adecuada, demostrada por un aclaramiento de creatinina ≥ 30 ml/min calculado mediante la fórmula de Cockcroft-Gault o medido en orina de 24 horas.
    7. El paciente debe tener una función hepática adecuada, demostrada por:
    • aspartato aminotransferasa (AST) ≤ 3,0 × LSN*
    • alanina aminotransferasa (ALT) ≤ 3,0 × LSN*
    • bilirrubina ≤ 1,5 x LSN*
    * A menos que se considere debido a afectación orgánica leucémica
    o Los pacientes < 75 años de edad pueden tener una bilirrubina ≤ 3,0 × LSN
    8. Las mujeres deben ser posmenopáusicas definidas como:
    • Edad >55 años con amenorrea durante al menos 12 meses sin otros motivos médicos.
    • Edad ≤ 55 años con amenorrea durante al menos 12 meses sin otros motivos médicos Y nivel de folitropina (FSH) > 40IU/L.
    OR
    • Quirúrgicamente estériles (ooforectomía bilateral, salpingectomía bilateral o histerectomía)
    OR
    • Mujeres en edad fértil deben practicar al menos uno de los controles de natalidad específicos, empezando el día 1 del estudio hasta al menos 90 días después de la última dosis del fármaco de estudio.
    9. Hombres sexualmente activos deben estar de acuerdo en tomar medidas de contracepción específicas desde el día 1 del estudio hasta al menos 90 días después de la última dosis del fármaco de estudio. Los hombres deben estar de acuerdo en abstenerse de la donación de esperma desde el inicio de la administración del fármaco de estudio hasta al menos 90 días después de la última dosis del fármaco.
    10. Mujeres en edad fértil deberán tener resultados negativos en las pruebas de embarazo realizadas:
    • En la selección, una muestra de suero obtenida durante los 14 días previos a la primera dosis del fármaco de estudio.
    • Antes de la dosis con una muestra de orina obtenida en el Ciclo 1 Día 1, si han pasado más de 7 días desde que se obtuvieron los resultados de la muestra de suero.
    11. El paciente deberá firmar voluntariamente y fechar un consentimiento informado aprobado por un Comité de Ética de la Investigación con medicamentos (CEIm) antes del inicio de cualquier procedimiento de selección o específico del estudio.
    E.4Principal exclusion criteria
    ● Subject has received treatment with the following:
    - A hypomethylating agent and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
    - CAR-T cell therapy
    - Experimental therapies for MDS or AML.
    ● Subject has history of myeloproliferative neoplasm (MPN).
    ● Subject has the following:
    - Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;;17) as per the NCCN Guidelines Version 2, 2016 for Acute Myeloid Leukemia.
    ● Subject has acute promyelocytic leukemia
    ● Subject has known active CNS involvement with AML.
    ● Subject is known to be positive for HIV (HIV testing is not required.)
    ● Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
    ● Subject has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
    ● Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
    ● Subject has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
    ● Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.
    ● Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
    ● Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
    ● Subject has a history of other malignancies within 2 years prior to study entry, with the exception of:
    - Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
    - Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    - Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
    ● Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)
    1. El paciente ha recibido tratamiento con lo siguiente:
    • Fármaco hipometilante o cualquier quimioterápico para síndrome mielodisplásico (SMD).
    • Tratamiento con células CAR-T
    • Tratamientos experimentales para MDS o LMA.
    2. El paciente tiene antecedente de neoplasia mieloproliferativa [NMP].
    3. El paciente tiene:
    • Una citogenética de riesgo favorable, como t(8;21), inv(16), t(16;16) o t(15;17) según las directrices de la NCCN, versión 2, 2016 para la leucemia mieloide aguda.
    4. El paciente padece leucemia promielocítica aguda
    5. El paciente presenta afectación activa confirmada del SNC por la LMA.
    6. Se sabe que el paciente es VIH-positivo (no es necesario un análisis del VIH)
    7. Se sabe que el paciente padece una infección por el virus de la hepatitis B o C, con la excepción de los que presenten una carga viral indetectable en los 3 meses anteriores (no es necesario un análisis de la hepatitis B o C). Podrán participar pacientes con indicios serológicos de vacunación previa contra el VHB [es decir, HBs Ag- y anti-HBs+]).
    8. El paciente ha recibido inductores fuertes o moderados de la CYP3A en los 7 días previos al comienzo del tratamiento del estudio.
    9. El paciente ha tomado pomelo, productos de pomelo, naranjas amargas (o mermelada de este tipo de naranjas) o carambola en los 3 días previos al comienzo del tratamiento del estudio.
    10. El paciente presenta un estado de discapacidad cardiovascular de clase ≥ 2 de la New York Heart Association. La clase 2 se define como un trastorno cardíaco en el que el paciente se encuentra bien en reposo pero presenta cansancio, palpitaciones, disnea y dolor de tipo anginoso al realizar una actividad física normal.
    11. El paciente presenta una enfermedad respiratoria crónica que requiere oxígeno continuo o tiene antecedentes importantes de enfermedad renal, neurológica, psiquiátrica, endocrinológica, metabólica, inmunitaria, hepática o cardiovascular, o cualquier otra afección que en opinión del investigador pueda afectar de manera adversa a su participación en este estudio.
    12. El paciente tiene un síndrome de malabsorción u otro trastorno que impida la administración por vía enteral.
    13. El paciente presenta signos de otra infección sistémica no controlada clínicamente importante con necesidad de tratamiento (viral, bacteriana o fúngica).
    14. El paciente tiene antecedentes de otras neoplasias malignas en los 2 años anteriores a la inclusión en el estudio, con la excepción de:
    • Carcinoma in situ del cuello uterino o la mama tratado adecuadamente;
    • Carcinoma basocelular o espinocelular localizado de la piel;
    • Neoplasia maligna previa confinada y resecada quirúrgicamente (o tratada con otras modalidades) con intención curativa.
    15. El paciente tiene un recuento de leucocitos > 25 × 109/l. (Se permite la hidroxicarbamida para cumplir este criterio.)
    E.5 End points
    E.5.1Primary end point(s)
    1. Rate of complete remission (CR) or complete remission with incomplete marrow recovery (CRi)
    2. Overall Survival (OS)
    1. La tasa de remisión completa (RC) o la tasa de remisión completa con recuperación incompleta de la médula (RCi)
    2. La supervivencia global (SG)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to 6 months after the first 225 subjects are randomized
    2. Measured up to 2 years after the last participant is randomized
    1. Hasta 6 meses después de que los primeros 225 sujetos fueron randomizados
    2. Medida hasta 2 años después de que el último participante es randomizado
    E.5.2Secondary end point(s)
    1. Event-Free Survival (EFS)
    2. CR + CRi rate by the initiation of Cycle 2
    3. Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form [SF] 7a and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core [EORTC QLQ-C30]).
    1. Supervivencia sin episodios (SSE)
    2. Tasa de remisión completa compuesta al inicio del ciclo 2
    3. Cuestionario breve del cansancio en el cáncer [SF] 7a del Patient Reported Outcomes Measurement Information System [PROMIS] y Cuestionario esencial de calidad de vida de la European Organization for Research and Treatment of Cancer [EORTC QLQ-C30]).
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Measured up to 2 years after the last participant is randomized
    2. 6 months after the last participant is randomized
    3. Measured at participant's Day 1 of Cycle 1 and at Day 1 of every Cycle thereafter for up to 3 years following the last subject last visit
    1. Medido hasta 2 años después de que el último participante sea randomizado
    2. 6 meses después de que el último participante sea randomizado
    3. Medido en el Día 1del Ciclo 1 del participante y en el Día 1 de cada Ciclo a partir de ese momento y hasta 3 años después del último sujeto última visita.
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarker, Exploratory
    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) No
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA82
    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
    Australia
    Brazil
    Canada
    China
    European Union
    Israel
    Japan
    Korea, Republic of
    Norway
    Puerto Rico
    Russian Federation
    South Africa
    Taiwan
    Turkey
    Ukraine
    United States
    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
    LVLS
    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 months3
    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 months3
    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: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 360
    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 state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 250
    F.4.2.2In the whole clinical trial 400
    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)
    After treatment discontinuation, subjects will be followed for, overall survival, progressive disease and post-therapy disease status (if applicable).
    Después de la interrupción del tratamiento, los sujetos serán seguidos para supervivencia global, progresión de la enfermedad y estado de enfermedad post-terapia (si corresponde)
    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 Decision2017-07-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-07-14
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA