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    Summary
    EudraCT Number:2015-004202-41
    Sponsor's Protocol Code Number:PONALFIL
    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:2016-02-03
    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 number2015-004202-41
    A.3Full title of the trial
    CONCURRENT PONATINIB WITH CHEMOTHERAPY FOR YOUNG ADULTS WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA.
    PONATINIB Y QUIMIOTERAPIA EN ADULTOS JÓVENES CON LEUCEMIA AGUDA LINFOBLÁSTICA CON CROMOSOMA FILADELFIA DE NUEVO DIAGNOSTICO.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    CONCURRENT PONATINIB WITH CHEMOTHERAPY FOR YOUNG ADULTS WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA.
    PONATINIB Y QUIMIOTERAPIA EN ADULTOS JÓVENES CON LEUCEMIA AGUDA LINFOBLÁSTICA CON CROMOSOMA FILADELFIA DE NUEVO DIAGNOSTICO.
    A.3.2Name or abbreviated title of the trial where available
    PONALFIL
    PONALFIL
    A.4.1Sponsor's protocol code numberPONALFIL
    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 SponsorFundación PETHEMA
    B.1.3.4CountrySpain
    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 supportARIAD
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCABYC, S.L.
    B.5.2Functional name of contact pointInvestigación clínica
    B.5.3 Address:
    B.5.3.1Street AddressAvenida Somosierra, 12. Portal Izqdo., 2ºG
    B.5.3.2Town/ citySan Sebastián de los Reyes (Madrid)
    B.5.3.3Post code28703
    B.5.3.4CountrySpain
    B.5.4Telephone number+34916590433-
    B.5.5Fax number+34916548969-
    B.5.6E-mailpatricia.diaz@cabyc.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name ICLUSIG® 15mg comprimidos
    D.2.1.1.2Name of the Marketing Authorisation holderARIAD PHARMACEUTICAL . INC.,
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/09/715
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPonatinib
    D.3.9.1CAS number 943319-70-8
    D.3.9.3Other descriptive namePONATINIB
    D.3.9.4EV Substance CodeSUB91901
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA.
    LEUCEMIA AGUDA LINFOBLÁSTICA CON CROMOSOMA FILADELFIA DE NUEVO DIAGNOSTICO
    E.1.1.1Medical condition in easily understood language
    NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA.
    LEUCEMIA AGUDA LINFOBLÁSTICA CON CROMOSOMA FILADELFIA DE NUEVO DIAGNOSTICO
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10000845
    E.1.2Term Acute lymphoblastic leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the response (complete hematologic response [CHR], complete cytogenetic response [CCyR], major molecular response [MMR], complete molecular response [CMR] and the event free survival (EFS) of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with newly diagnosed Ph+ (BCR-ABL) ALL .
    Evaluar la respuesta (respuesta hematológica completa [RHC], respuesta citogenética completa [RCyC], respuesta moleclar mayor [RMM] y respuesta molecular completa [RMC]) y la supervivencia libre de eventos (SLE) de la combinación de Ponatinib con quimioterapia estándar (de acuerdo con el ensayo PETHEMA LAL Ph08) en pacientes jóvenes con LAL Ph+ (BCR-ABL) de nuevo diagnóstico.
    E.2.2Secondary objectives of the trial
    1. To evaluate the rate of patients receiving an allogeneic hematopoietic stem cell transplant (alloHSCT) in first CR
    2. To evaluate the frequency of MMR and CMR at the time of alloHSCT
    3. To evaluate the transplant-related mortality (TRM)
    4. To evaluate the CR duration and overall survival (OS) of the combination of ponatinib with standard chemotherapy (according to PETHEMA ALL Ph08 trial) in young patients with Ph+ (BCR-ABL) ALL.
    5. To evaluate the outcome measures (CR duration, OS and EFS) in context of those observed in the PETHEMA ALL Ph08 trial.
    6. To observe the type and number of BCR-ABL kinase domain mutations developing during and after the study.
    7. To evaluate side effects, adverse events (AE) and serious AE (SAE).
    1. Evaluar la tasa de pacientes que reciben un TPH en primera RC.
    2. Evaluar la frecuencia de RMM y de RMC en el momento del TPH.
    3. Evaluar la mortalidad relacionada con el trasplante (MRT)
    4. Evaluar la duración de la RC y la SG de la combinación de Ponatinib con quimioterapia estándar (de acuerdo con el ensayo PETHEMA LAL Ph08) en pacientes jóvenes con LAL Ph+ (BCR-ABL).
    5. Evaluar la duración de la RC, SG y suervivencia libre de enfermedad.
    6. Determinar el número y tipo de mutaciones en el dominio BCR-ABL kinasa que se desarrollan durante y después del estudio.
    7. Evaluar los efectos secundarios, los acontecimientos adversos (AA) y los acontecimientos adversos graves (SAE)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18-55 yr.
    2. De novo Ph+ (BCR-ABL)ALL,
    3. ECOG score ?2 unless due to ALL
    4. Absence of significant liver disease, as defined by the following criteria: total serum bilirubin ?1.5 x upper limit of normal (ULN), unless due to Gilbert?s syndrome, alanine aminotransferase (ALT) ?2.5 × ULN or ?5 x ULN if leukemic involvement of the liver is present, and aspartate aminotransferase (AST) ?2.5 × ULN or ?5 x ULN if leukemic involvement of the liver is present.
    5. Adequate pancreatic function as defined by serum lipase and amylase ?1.5 × ULN.
    6. No history of dyslipidemia, hypertension, thrombotic events or cardiac disease.
    7. For females of childbearing potential, a negative pregnancy test must be documented prior to randomization. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from randomization through 4 months after the end of treatment.
    8. Informed consent signed, according to national regulation.
    1. Edad 18-55 años.
    2. LAL Ph + (BCR-ABL) de novo
    3. Puntuación ECOG ?2 a a menos que se deba a LAL
    4. Ausencia de hepatopatía significativa definida por los siguientes criterios: bilirrubina sérica total ?1.5 x por encima del límite superior de normalidad (LSN) a menos que se deba al Síndrome de Gilbert, ALT ?2.5 × LSN o ?5 x LSN si hay infiltración leucémica, y AST ?2.5 × LSN o ?5 x LSN si hay infiltración leucémica del hígado.
    5. Función pancreática adecuada definida por lipasa sérica y amilasa ?1.5 × LSN.
    6. Sin historial de dislipidemia, hipertensión, acontecimientos trombóticos o enfermedad cardiaca.
    7. Para mujeres con capacidad de gestación, se tiene que documentar una prueba negativa de embarazo antes de la inclusión. Los pacientes tanto mujeres como varones que sean fértiles, tienen que estar de acuerdo en utilizar un método eficaz de contracepción con sus compañeros sexuales desde el momento de la randomización y hasta 4 meses tras el final del tratamiento.
    8. Consentimiento informado firmado, de acuerdo a la regulación nacional.
    E.4Principal exclusion criteria
    1. Lymphoid blast crisis of CML,
    2. WHO performance status ? 50% (Karnofsky) or ? 3 (ECOG).
    3. Active HBV or HCV hepatitis, or AST/ALT ? 2.5 x ULN and bilirubin ? 1.5 x ULN.
    4. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.
    5. History of alcohol abuse.
    6. Ongoing or active infections.
    7. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
    8. Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
    - Any history of myocardial infarction, stroke, or revascularization,
    - Unstable angina or transient ischemic attack within 6 months prior to enrollment
    - Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards
    - History of clinically significant (as determined by the treating physician) atrial arrhythmia
    - Any history of ventricular arrhythmia
    - Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism.
    9. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
    10. Taking medications that are known to be associated with torsades de pointes.
    11. Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
    12. Creatinine levels > 2.5mg/dl or glomerular filtration rate (GFR) < 20 ml/min or proteinuria >3.5 g/day.
    13. Gastrointestinal (GI) function impairment, or a GI disease that may significantly alter the absorption of study drugs.
    14. Patients who are currently receiving treatment with any of the medications with potential to prolong QT interval (listed in Appendix 4) if the medications cannot be either discontinued or switched to a different medication prior to starting study drug.
    15. Patients who have received any investigational drug ? 4 weeks.
    16. Patients who have undergone major surgery ? 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
    17. Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs. prior to administration of Ponatinib). Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 4 months following discontinuation of study drugs.
    18. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
    19. Patients unwilling or unable to comply with the protocol.
    1. Crisis blástica linfoide de la LMC,
    2. Estado Funcional de la OMS ? 50% (Karnofsky) o ? 3 (ECOG)
    3. Hepatitis VHB o VHC en actividad, o AST/ALT ? 2.5 x LSN y bilirrubina ? 1.5 x LSN.
    4. Antecedente de pancreatitis aguda en el año anterior a la inclusión en el estudio o antecedentes de pancreatitis crónica.
    5. Antecedentes de alcoholismo.
    6. Infecciones activas o en marcha.
    7. Hipertrigliceridemia no controlada (triglicéridos >450 mg/dL).
    8. Enfermedad cardiovascular clínicamente significativa, no controlada o activa, incluyendo específicamente, pero no restringida a:
    - Cualquier antecedente de infarto de miocardio, ictus o revascularización,
    - Angina inestable o ictus isquémico transitorio en los 6 meses anteriores a la inclusión.
    - Insuficiencia cardiaca congestiva en los 6 meses previos a la inclusión, o fracción de eyección ventricular izquierda (FEVI) inferior al límite de la normalidad según los estándares institucionales locales.
    - Antecedentes de arritmia auricular clínicamente significativa (según lo determinado por el médico tratante).
    - Cualquier antecedente de arritmias ventriculares.
    - Cualquier antecedente de tromboembolia venosa incluyendo trombosis venosa profunda o embolia pulmonar.
    9. Hipertensión no controlada (presión diastólica >90 mm Hg; sistólica >140 mm Hg). Los pacientes hipertensos deben estar tratados al ingreso del estudio para tener controlada la presión arterial.
    10. Consumo de fármacos de los que se sabe que están asociados con taquicardias ventriculares polimorfas (torsade de pointes).
    11. Tomar cualquier medicamento o suplementos de fitoterapia de los que se conoce que son potentes inhibidores de la CYP3A4 al menos en los 14 días previos a la primera dosis de Ponatinib.
    12. Creatinina > 2.5 mg/dl o filtrado glomerular (FG) < 20 ml/min o proteinuria >3.5 g/día.
    13. Deterioro de la función gastrointestinal (GI) o enfermedad GI que pueda alterar significativamente la absorción de los fármacos del estudio.
    14. Pacientes que estén recibiendo actualmente tratamiento con cualquiera de los medicamentos con capacidad de prolongar el intervalo QT (enumerados en el Anexo 4) si estos no se pueden suspender o cambiarse a otros fármacos antes de comenzar con la medicación del estudio.
    15. Pacientes que hayan recibido cualquier fármaco en investigación ? 4 semanas antes de comenzar con la medicación del estudio.
    16. Pacientes que se hayan sometido a cirugía mayor ? 2 semanas antes de comenzar con la medicación del estudio o que no se hayan recuperado de los efectos secundarios de tal cirugía.
    17. Mujeres que estén embarazadas o en período de lactancia y pacientes adultos con capacidad reproductiva que no estén utilizando métodos eficaces de control de natalidad (las mujeres con capacidad de gestación deben tener una prueba de embarazo negativa en las 48 h anteriores a la administración de Ponatinib). Las mujeres posmenopáusicas deben estar amenorreicas durante al menos 12 meses para ser consideradas como mujeres sin capacidad de gestación. Los pacientes varones y mujeres deben estar de acuerdo en emplear métodos anticonceptivos de barrera eficaces a lo largo del estudio y durante un máximo de hasta 4 meses tras la discontinuación del fármaco del estudio.
    18. Pacientes con antecedentes de otra neoplasia maligna que actualmente sea clínicamente significativa o que precise intervención activa en estos momentos.
    19. Pacientes que no quieren o no pueden cumplir con el protocolo.
    E.5 End points
    E.5.1Primary end point(s)
    All the patients who have been enrolled will be counted for any efficacy and safety observation and variable, according to the intention-to-treat principle. The frequency of the AE and the rate of permanent discontinuation for AE will also be calculated based on all patients. The compliance to the dose (dose density) will be calculated by dividing the administered dose by the dose that was actually given, over the whole treatment period. The kinetics of hematologic, cytogenetic and molecular responses, i.e. the time to achieve the respective responses, will be calculated using Kaplan & Meier?s product limit estimates. Response duration, failure-free survival, event-free survival and overall survival will be calculated using the same method. For comparisons of OS, EFS and FFS and response duration the Log-Rank will be used. Cumulative Incidence curves (e.g. for relapse rate) will be estimated using the proper non-parametric method. The Gray test will be applied for significance tests on cumulative incidence curves. All analyses will be performed using the SPSS package; all tests will be two-sided, at a significance level of 0.05.
    Todos los pacientes incluidos contarán para cualquier observación y para la variable de eficacia y seguridad, de acuerdo al principio de intención de tratar.
    La frecuencia de AA y la tasa de discontinuación permanente por AA se calculará en base a todos los pacientes.
    El cumplimiento de la dosis prescrita (densidad de la dosis) se calculará dividiendo la dosis teórica administrada por la dosis realmente administrada, durante todo el período de tratamiento.
    La cinética de las respuestas hematológica, citogenética y molecular, p. ej., tiempo en alcanzar las respuestas respectivas, se calcularán mediante el método de Kaplan-Meier.
    La duración de la respuesta, la supervivencia sin fracaso, la supervivencia sin acontecimientos y la supervivencia global se calcularán utilizando el mismo método.
    Para comparaciones de SG, SLE y la duración de la RC se empleará el método de Log-Rank.
    Las curvas de incidencia acumulada (p.ej. para la tasa de recidiva) se estimarán utilizando el método no paramétrico apropiado.
    La prueba de Gray se aplicará para las pruebas de significación estadística en las curvas de incidencias acumulada.
    Todos los análisis se realizarán utilizando el paquete SPSS; todas las pruebas serán de dos colas, con nivel de significación de 0.05.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The expected period of enrollment will be 1.5 years (18 month)
    The overall duration of the therapy will be approximately 2.5 years:
    -expected time interval between induction and HSCT: 0.5 years;
    -duration of maintenance therapy with ponatinib after HSCT: 2 years
    -In patients submitted to alloHSCT, maintenance therapy of 2 years with ponatinib only in patients with MRD + (patients will be monthly monitored during the following 2 years from alloHSCT to detect MRD in case of relapse)
    The period of follow-up after treatment will be of 1 year
    With an expected period of enrollment of 1.5 years, and a period of follow-up after treatment in case of relapse of 1 year, the duration of the study will be approximately 5 to 7.5 years (enrollment + therapy duration + follow-up).
    Se espera un período de inclusión de 1.5 años (18 meses)
    La duración global del tto será de aproximadamente 2.5 años:
    -Intervalo de tiempo esperado entre la inducción y el TPH: 0.5 años;
    -Duración del tto de mantenimiento con Ponatinib tras el TPH: 2 años
    -En pacientes sometidos a un aloTPH, tto de mantenimiento de 2 años con Ponatinib solo en pacientes con ER+ (los pacientes se monitorizarán mensualmente durante los siguientes 2 años desde el aloTPH para detectar ER en caso de recidiva).
    El período de seguimiento tras el tratamiento será de 1 año
    Tras un período de inclusión esperado de 1,5 años y un período de seguimiento tras el tto en caso de recidiva de 1 año, la duración del estudio será de aproximadamente 5 a 7,5 años (inclusión + duración del tratamiento + seguimiento)
    E.5.2Secondary end point(s)
    The expected period of enrollment will be 1.5 years (18 month)
    The overall duration of the therapy will be approximately 2.5 years:
    -expected time interval between induction and HSCT: 0.5 years;
    -duration of maintenance therapy with ponatinib after HSCT: 2 years
    -In patients submitted to alloHSCT, maintenance therapy of 2 years with ponatinib only in patients with MRD + (patients will be monthly monitored during the following 2 years from alloHSCT to detect MRD in case of relapse)
    The period of follow-up after treatment will be of 1 year
    With an expected period of enrollment of 1.5 years, and a period of follow-up after treatment in case of relapse of 1 year, the duration of the study will be approximately 5 to 7.5 years (enrollment + therapy duration + follow-up).
    Se espera un período de inclusión de 1.5 años (18 meses)
    La duración global del tto será de aproximadamente 2.5 años:
    -Intervalo de tiempo esperado entre la inducción y el TPH: 0.5 años;
    -Duración del tto de mantenimiento con Ponatinib tras el TPH: 2 años
    -En pacientes sometidos a un aloTPH, tto de mantenimiento de 2 años con Ponatinib solo en pacientes con ER+ (los pacientes se monitorizarán mensualmente durante los siguientes 2 años desde el aloTPH para detectar ER en caso de recidiva).
    El período de seguimiento tras el tratamiento será de 1 año
    Tras un período de inclusión esperado de 1,5 años y un período de seguimiento tras el tto en caso de recidiva de 1 año, la duración del estudio será de aproximadamente 5 a 7,5 años (inclusión + duración del tratamiento + seguimiento)
    E.5.2.1Timepoint(s) of evaluation of this end point
    The expected period of enrollment will be 1.5 years (18 month)
    The overall duration of the therapy will be approximately 2.5 years:
    -expected time interval between induction and HSCT: 0.5 years;
    -duration of maintenance therapy with ponatinib after HSCT: 2 years
    -In patients submitted to alloHSCT, maintenance therapy of 2 years with ponatinib only in patients with MRD + (patients will be monthly monitored during the following 2 years from alloHSCT to detect MRD in case of relapse)
    The period of follow-up after treatment will be of 1 year
    With an expected period of enrollment of 1.5 years, and a period of follow-up after treatment in case of relapse of 1 year, the duration of the study will be approximately 5 to 7.5 years (enrollment + therapy duration + follow-up).
    Se espera un período de inclusión de 1.5 años (18 meses)
    La duración global del tto será de aproximadamente 2.5 años:
    -Intervalo de tiempo esperado entre la inducción y el TPH: 0.5 años;
    -Duración del tto de mantenimiento con Ponatinib tras el TPH: 2 años
    -En pacientes sometidos a un aloTPH, tto de mantenimiento de 2 años con Ponatinib solo en pacientes con ER+ (los pacientes se monitorizarán mensualmente durante los siguientes 2 años desde el aloTPH para detectar ER en caso de recidiva).
    El período de seguimiento tras el tratamiento será de 1 año
    Tras un período de inclusión esperado de 1,5 años y un período de seguimiento tras el tto en caso de recidiva de 1 año, la duración del estudio será de aproximadamente 5 a 7,5 años (inclusión + duración del tratamiento + seguimiento)
    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 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 Yes
    E.6.13.1Other scope of the trial description
    Además de evaluar la respuesta (respuesta hematológica completa [RHC], se estudiará la respuesta citogenética completa [RCyC], respuesta moleclar mayor [RMM] y respuesta molecular completa [RMC]) y la supervivencia libre de eventos (SLE) de la combinación de Ponatinib con quimioterapia estándar en pacientes jóvenes con LAL Ph+ (BCR-ABL) de nuevo diagnóstico.
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned11
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last patient's last visit.
    Última visita del último paciente.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    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: 30
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    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)
    Ponatinib will not be discontinued during the preparation for HSCT.
    -After alloHSCT, If MRD - : no therapy. If MRD +, repeat the assessment. If remains +, Ponatinib 30 mg/d, po, during the 1st year. Reduce the ponatinib dose to 15 mg/d during the 2nd year.
    -After autoHSCT: Ponatinib: 30 mg/d, PO, mercaptopurine, (40mg/m2/d, PO) and methotrexate (15mg/m2/week, IM), during the 1st year after HSCT. Ponatinib 15 mg/d in the 2nd year in patients with sustained molecular response.
    No se discontinuará Ponatinib durante la preparación para el TPH.
    -Tras el aloTPH, Si ER-, no dar tratamiento. Si ER+, repetir la evaluación. Si permanece +, Ponatinib 30 mg/día PO durante el 1er año. Reducir dosis de Ponatinib a 15 mg/día durante el 2º año.
    -Tras el autoTPH: Ponatinib: 30 mg/d, PO, mercaptopurina, (40mg/m2/d, PO) y metotrexato (15 mg/m2/semana, IM), durante el primer año tras el TPH. Ponatinib a 15 mg/d en el segundo año en pacientes con respuesta molecular sostenida.
    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 Decision2016-03-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-11
    P. End of Trial
    P.End of Trial StatusOngoing
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