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    Summary
    EudraCT Number:2012-002934-35
    Sponsor's Protocol Code Number:NOPHO-DBH-AML-2012
    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:2016-12-27
    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 number2012-002934-35
    A.3Full title of the trial
    NOPHO-DBH AML 2012 Protocol
    Research study for treatment of children and adolescents with acute myeloid leukaemia 0-18 years
    Protocolo NOPHO-DBH AML 2012
    Estudio de investigación para el tratamiento de niños y adolescentes con leucemia mieloide aguda de 0 a 18 años
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Research study for treatment of children and adolescents with acute myeloid leukaemia 0-18 years
    Estudio de investigación para el tratamiento de niños y adolescentes con leucemia mieloide aguda de 0 a 18 años
    A.3.2Name or abbreviated title of the trial where available
    AML 2012
    A.4.1Sponsor's protocol code numberNOPHO-DBH-AML-2012
    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 SponsorVästra Götaland Regionen
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportVästra Götaland Regionen
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportRegion Skåne
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportStockholms läns landsting
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportLandstinget i Östergötland
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportLandstinget i Uppsala
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportVästerbottens läns landsting
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportRegion Hovedstaden
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportRigion Midt
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportHong Kong Hospital Authority
    B.4.2CountryHong Kong
    B.4.1Name of organisation providing supportHelse Sör-Öst
    B.4.2CountryNorway
    B.4.1Name of organisation providing supportHelse Vest
    B.4.2CountryNorway
    B.4.1Name of organisation providing supportHelse Midt-Norge
    B.4.2CountryNorway
    B.4.1Name of organisation providing supportHelse Nord
    B.4.2CountryNorway
    B.4.1Name of organisation providing supportMinistry of Welfare
    B.4.2CountryIceland
    B.4.1Name of organisation providing supportMinistry of Education and Science
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportRijksinstituut voor Ziekte- en Invaliditeitsverzekering/Institut National d'Assurance Maladie-Invalidité
    B.4.2CountryBelgium
    B.4.1Name of organisation providing supportHospital district of Helsinki University Central Hospital
    B.4.2CountryFinland
    B.4.1Name of organisation providing supportHospital district of Tampere University Central Hospital
    B.4.2CountryFinland
    B.4.1Name of organisation providing supportHospital district of Kuopio University Central Hospital
    B.4.2CountryFinland
    B.4.1Name of organisation providing supportHospital district of Oulo University Central Hospital
    B.4.2CountryFinland
    B.4.1Name of organisation providing supportHospital district of Turku University Central Hospital
    B.4.2CountryFinland
    B.4.1Name of organisation providing supportEstonian health insurance fund
    B.4.2CountryEstonia
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVästra Götaland regionen
    B.5.2Functional name of contact pointBarncancerforskningscentrum
    B.5.3 Address:
    B.5.3.1Street AddressQueen Silvias University Hospital
    B.5.3.2Town/ cityGothenburg
    B.5.3.3Post code41685
    B.5.3.4CountrySweden
    B.5.4Telephone number46313434000
    B.5.6E-mailjonas.abrahamsson@vgregion.se
    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 Fludarabina SPI
    D.2.1.1.2Name of the Marketing Authorisation holderSandoz Farmacéutica, S.A
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Powder for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFLUDARABINE PHOSPHATE
    D.3.9.1CAS number 75607-67-9
    D.3.9.4EV Substance CodeSUB13897MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 DaunoXome
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences S.L.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Concentrate for emulsion for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDAUNORUBICIN
    D.3.9.1CAS number 20830-81-3
    D.3.9.4EV Substance CodeSUB06917MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 Citarabina Pfizer
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer S.L.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCYTARABINE
    D.3.9.1CAS number 147-94-4
    D.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number20 to 100
    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 Mitoxantrona Sandoz
    D.2.1.1.2Name of the Marketing Authorisation holderSandoz Farmacéutica, S.A.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMitoxantrone hydrochloride
    D.3.9.1CAS number 65271-80-9
    D.3.9.3Other descriptive nameMITOXANTRONE
    D.3.9.4EV Substance CodeSUB09012MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mEq/mg milliequivalent(s)/milligram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Etoposido Smaller
    D.2.1.1.2Name of the Marketing Authorisation holderLaboratorios SMALLER, S.A.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNETOPOSIDE
    D.3.9.3Other descriptive nameEtoposide
    D.3.9.4EV Substance CodeSUB07337MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 50
    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
    Acute myeloid leukemia
    Leucemia Mieloide Aguda
    E.1.1.1Medical condition in easily understood language
    Acute myeloid leukemia
    Leucemia Mieloide Aguda
    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 AML 2012 study is a treatment and research protocol with the overall aim of improving prognosis for children and adolescents with AML. This is to be achieved by better risk stratification based on MRD quantification and more intensive induction compared to previous NOPHO protocols.
    Specific research aims are
    1) To investigate if DaunoXome® has a higher efficacy than Mitoxantrone, when given in course 1 for treatment of pediatric AML
    2) To investigate if FLADx has a higher efficacy than ADxE when given as the second induction course for treatment of pediatric AML
    3) To investigate the correlation between MRD measurement by PCR and flow cytometry and the prognostic impact of MRD with either method after course 1 and 2 respectively.
    El estudio AML 2012 es un protocolo de tratamiento e investigación con el objetivo principal de mejorar el pronóstico para niños y adolescentes con LMA. Esto es para conseguir mediante un mayor riesgo de estratificación basado en una cuantificación de enfermedad residual mínima y una inducción más intensiva comparados con otros protocolos previos NOPHO.
    Los objetivos específicos de la investigación son:
    1) Investigar si DaunoXome tiene una mayor eficacia que MItoxantrone, cuando son administrados en el ciclo 1 en el tratamiento de LMA pediátrica.
    2) Investigar si FLADx tiene una mayor eficacia que ADxE cuando es administrado como segundo ciclo de inducción en el tratamiento de LMA pediátrica.
    3) Investigar la correlación entre la medida de la enfermedad residual mínima mediante PCR y citometría de flujo y el impacto pronóstico de la enfermedad residual mínima con cualquiera de los métodos después del ciclo uno y el ciclo dos respectivamente.
    E.2.2Secondary objectives of the trial
    The protocol will compare the efficacy and toxicity of the treatment between the randomised arms and with the previous NOPHO-AML protocols with the aims of
    1) Improving both EFS and OS as compared to NOPHO-AML 93 and 2004.
    2) Improving EFS and OS for patients with intermediate response (5-14.9%) blasts after course 1 and patients with t(8;21).
    3) Achieving improved anti-leukaemic effect with no increase or a decrease in early toxic deaths and deaths in CR.
    4) Comparing outcome in subgroups of patients as defined by characteristics of both patients and disease such as age, FAB type and cytogenetics (e.g. t(8;21, inv(16) and MLL rearrangements).
    5) Compare the incidence of severe infections and severe organ toxicity in the treatment arms and with previous protocols
    El protocolo también va a comparar la eficacia y toxicidad del tratamiento entre los brazos aleatorizados con los protocolos previos de NOPHO-AML con los objetivos de:
    1) Mejorar la supervivencia libre de progresión y la supervivencia total comparada con NOPHO-AML 93 y 2004.
    2) Mejorar la supervivencia libre de progresión y supervivencia total en pacientes con una respuesta intermedia (5-14 %) después del ciclo 1 y pacientes con t(8;21)
    3) Conseguir mejorar el efecto antileucémico con un no crecimiento o decrecimiento en muertes tempranas toxicas y muertes en remisión completa.
    4) Comparar el resultado en subgrupos de pacientes definidos mediante las características de pacientes y enfermedades como la edad, tipos de FAB y citogenéticos (ejemplo t8;21, inv(16) y reestructuración de MLL).
    5) Comparar la incidencia de las infecciones severas y la toxicidad orgánica severa en los brazos de tratamiento y con protocolos previos.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) AML as defined by the diagnostic criteria in the protocol
    2) Age < 19 years at time of diagnosis
    3) Written informed consent
    1) LMA es definida mediante los criterios de diagnóstico en la sección 16
    2) Edad < 19 años en el momento del diagnóstico
    3) Consentimiento Informado firmado.
    E.4Principal exclusion criteria
    1) Previous chemotherapy or radiotherapy. This includes patient with secondary AML after previous cancer therapy. They can be treated according to the protocol but will not be included in the study population. Secondary AML has a poorer response to chemotherapy but may benefit from SCT if the procedure can be tolerated.
    2) AML secondary to previous bone marrow failure syndrome.
    3) Down syndrome (DS). Patients with myeloid leukaemia of Down syndrome are recommended to be treated according to the international ML-DS protocol. Patients with AML and DS older than 5 years who often lack GATA1 mutation and do not have typical myeloid leukaemia of DS may be treated according to the protocol but will not be included in the study population.
    4) Acute promyelocytic leukaemia (APL). These patients are recommended treatment according to the international APL Study.
    5) Myelodysplastic syndrome (MDS). These patients are recommended treatment according to EWOG-MDS.
    6) Juvenile Myelomonocytic Leukaemia (JMML). These patients are recommended treatment according to EWOG-MDS.
    7) Known intolerance to any of the chemotherapeutic drugs in the protocol.
    8) Fanconi anaemia.
    9) Major organ failure precluding administration of planned chemotherapy.
    10) Positive pregnancy test .
    11) Lactating female or female of childbearing potential not using adequate contraception.
    1) Quimioterapia o radioterapia previa. Esto incluye pacientes con LMA secundaria después de una terapia anti cáncer previa. Ellos pueden ser tratados de acuerdo con el protocolo, pero no serán incluidos en la población de estudio. LMA secundaria tiene una peor respuesta a la quimioterapia, pero puede beneficiarse del trasplante de células madre si el procedimiento es tolerado.
    2) LMA secundaria previa al síndrome de insuficiencia de la médula ósea.
    3) Síndrome de Down (SD). Pacientes Síndrome de Down con Leucemia mieloide son recomendables para ser tratados de acuerdo con el protocolo internacional ML-DS. Pacientes con LMA y SD mayores de 5 años que normalmente carecen de la mutación GATA1 y no tienen leucemia mieloide aguda de síndrome de Down, pueden ser tratados de acuerdo al protocolo, pero no pueden ser incluidos en la población del estudio.
    4) Leucemia promielocítica aguda. Estos pacientes son recomendados para el tratamiento de acuerdo con el estudio internacional LPA
    5) Síndrome Mielodisplástico (SMD). Estos pacientes son recomendados para el tratamiento de acuerdo con EWOG-MSD.
    6) Leucemia Mielomonocítica Juvenil (LMMJ). Estos pacientes son recomendados para el tratamiento de acuerdo con EWOG-MDS.
    7) Intolerancia conocida a alguna de las drogas de quimioterapia descritas en el protocolo.
    8) Anemia de Fanconi.
    9) Fallo orgánico importante descartando la administración de quimioterapia planificada.
    10) Test de embarazo positivo
    11) Mujeres en periodo de lactancia o mujeres en edad fértil que no usan un adecuado método anticonceptivo.
    E.5 End points
    E.5.1Primary end point(s)
    1) The fraction of patients who achieve an MRD level below 0.1%, as quantified by flow cytometry, after the first induction course. (aim 1)
    2) The fraction of patients who achieve an MRD level below 0.1%, as quantified by flow cytometry, after the second induction course (aim 2)
    3) For patients with fusion genes MRD levels after course 1 and 2 (aim 3)
    1) La fracción de pacientes que alcanza un nivel de enfermedad residual mínima por debajo del 0,1%, tal como se cuantifica por citometría de flujo, después del primer ciclo de inducción. (Objetivo 1)
    2) La fracción de pacientes que alcanza un nivel de enfermedad residual mínima por debajo del 0,1%, cuantificado por citometría de flujo, después del segundo ciclo de inducción (objetivo 2)
    3) Para pacientes con fusión de genes, los niveles de enfermedad residual mínima después de los ciclos 1 y 2 (objetivo 3)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Aim 1 and 3. At day 22 after course 1.
    Aim 2 and 3. At day 22 after course 2 and immediately prior to the third course (6-8 weeks from diagnosis)
    Objetivo 1 y 3. El día 22 después del ciclo 1.
    Objetivo 2 y 3. El día 22 después del ciclo 2 e inmediatamente anterior al tercer ciclo (6-8 semanas desde el diagnóstico)
    E.5.2Secondary end point(s)
    1. Event-free survival and overall survival at five years.
    2. The median MRD after course 1 and course 2.
    3. The rate of CR after one and two induction courses.
    4. Cardiac function after one and five years.
    5. Frequency of severe adverse events as defined in 14.2.3, early death and death in CR.
    1. Supervivencia libre de eventos y supervivencia global a los cinco años.
    2. La media de enfermedad residual mínima después del ciclo 1 y ciclo 2.
    3. La tasa de remisión completa después de uno y dos ciclos de inducción.
    4. Función cardíaca después de uno y cinco años.
    5. Frecuencia de eventos adversos severos como se define en 14.2.3, muerte temprana y muerte en remisión completa.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Five years from diagnosis or at time of event.
    2) Within 6-8 weeks from diagnosis
    3) Within 6-8 weeks from diagnosis
    4) One and five years from diagnosis
    5) After each course (every 3-4 weeks for five courses) and cumulative within five years
    1) Cinco años desde el diagnóstico o en el momento del evento.
    2) Dentro de 6-8 semanas desde el diagnóstico
    3) Dentro de 6-8 semanas del diagnóstico
    4) Uno y cinco años después del diagnóstico
    5) Después de cada ciclo (cada 3-4 semanas para cinco ciclo) y acumulativo dentro de cinco años
    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 No
    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) 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 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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA33
    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
    Hong Kong
    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 trial will end at LVLS which is five years from diagnosis but patients will be followed for long-term effects afterwards.
    El ensayo terminará en la última visita del último paciente, que es de cinco años desde el diagnóstico, pero los pacientes serán sometidos a un seguimiento para evaluar los efectos a largo plazo.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years10
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 325
    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) Yes
    F.1.1.3.1Number of subjects for this age range: 3
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 60
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 150
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 85
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 25
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    The trial includes young children. The exact number in the age groups (and thus the number unable to give/participate in giving consent) is not possible to give as the study is population-based in all countries at least below the age of 16.
    El ensayo incluye niños pequeños. El número exacto de pacientes en cada grupo (incluyendo los pacientes incapaces de dar el consentimiento) no se puede dar ya que la población de estudio se basa en todos los países al menos por debajo de 16 años.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 265
    F.4.2.2In the whole clinical trial 325
    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)
    All patients will be followed up within the trial for five years after diagnosis which is approximately 4,5 years after end of therapy. After this time patients will be followed according to national guidelines for this patient group.
    Todos los pacientes serán sometidos a seguimientos dentro del ensayo durante 5 años después del diagnóstico que es aproximadamente 4,5 años después del final de la terapia. Después de este tiempo a los pacientes se les hará un seguimiento de acuerdo con las guías nacionales para este grupo de pacientes.
    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 Decision2017-03-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-02-15
    P. End of Trial
    P.End of Trial StatusOngoing
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