E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukemia (AML) is a 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. |
La leucemia mieloide aguda (LMA) es un cáncer de la línea mieloide de las células de sangre, caracterizado por el rápido crecimiento de las células blancas de la sangre anormales que se acumulan en la médula ósea e interfieren con la producción de células sanguíneas normales. |
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E.1.1.1 | Medical condition in easily understood language |
Acute myeloid leukemia (AML) is a cancer of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and stop normal blood cells from forming. |
LMA es un cáncer de las células de la sangre, causado por un crecimiento rápido de cél. blancas de sangre anormales que se acumulan en la médula ósea y detienen la formación de cél. de sangre normales |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to compare the overall survival between Arm A and Arm C. |
El objetivo principal es comparar la supervivencia global entre el grupo A y el grupo C. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the response rate of CR, CRp, PR, HI, SD and their corresponding durations, transfusion requirements, number of hospitalized days, 1-year survival and safety. |
Los objetivos secundarios son evaluar la tasa de respuesta de RC, RCp, RP, MH, EE y sus correspondientes duraciones, los requisitos de transfusión, el número de días de hospitalización, la supervivencia a 1 año y la seguridad. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The portion of the study referred to ?lead in ? in the protocol is technically a substudy. It was the non-randomized portion of the study which preceded the Phase 3 randomized part of the study. Twenty one (21) patients were enrolled to confirm the safety and tolerability of the treatment of sapacitabine given in alternating cycles with decitabine (Arm A) in the multicentre setting. Prior to initiating the Phase 3 part of the study, the DSMB reviewed the results and agreed that the treatment regimen of sapacitabine given in alternating cycles with decitabine was safe and tolerable for use in the phase 3 randomised part of the study. |
La parte del estudio referenciada como "fase preliminar" en el protocolo es técnicamente un subestudio. Era la parte no aleatoria del estudio que precedía la Fase 3 aleatorizada del estudio. Se inscribieron 21 pacientes para confirmar la seguridad y la tolerabilidad de la administración de sapacitabina en ciclos alternos con decitabina (Grupo A) en el ámbito multicéntrico. Antes de iniciar la Fase III del estudio, el DSMB revisó los resultados y acordó que el régimen de tratamiento de sapacitabina adminstrado con ciclos alternos de decitabina era seguro y tolerado para el uso en la parte de la fase 3 aleatorizada del estudio. |
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E.3 | Principal inclusion criteria |
?A histologically or pathologically confirmed diagnosis of AML based on WHO classification which has not been treated by any systemic therapy administered orally, intravenously or subcutaneously (except hydroxyurea) ?Age >= 70 years for whom the treatment of choice is low-intensity therapy by investigator assessment or who are not willing to receive intensive induction therapy recommended by investigator ?Eastern Cooperative Oncology Group (ECOG) performance status 0-2 ?Creatinine <1.5 x institutional upper limit of normal (ULN) ?Total bilirubin or direct bilirubin < 1.5 x ULN ?Alanine aminotransferase (ALT or SGPT)< 2 x ULN ?Life expectancy reasonably adequate for evaluating the treatment effect ?Patient must be able to swallow capsules ?Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments ?All men of reproductive potential must agree to practice effective contraception for 4 weeks prior to study entry, during the entire study period and for 2 months after the study unless documentation of infertility exists ?Ability to understand and willingness to sign the informed consent form |
-Diagnóstico de LMA confirmado histológica o patológicamente, de acuerdo con la clasificación de la OMS, que no haya sido tratado con ninguna terapia sistémica administrada por vía oral, intravenosa o subcutánea (excepto hidroxiurea). -Edad ? 70 años para quienes la elección de tratamiento sea la terapia de baja intensidad, según la evaluación del investigador, o que no deseen recibir terapia de inducción intensiva recomendada por el investigador. -Calidad de vida según Eastern Cooperative Oncology Group (ECOG) de 0-2 (consulte el Anexo B). -Creatinina < 1,5 x límite superior de lo normal (ULN) de la institución -Bilirrubina total y bilirrubina directa < 1,5 x ULN -Alanina aminotransferasa (ALT o SGPT) < 2 x ULN -Esperanza de vida razonablemente adecuada para evaluar el efecto del tratamiento. -El paciente debe ser capaz de tragar cápsulas. -Deben haber transcurrido al menos 2 semanas desde que los pacientes se hayan sometido a una cirugía importante, radioterapia o participación en otros estudios de investigación, y se hayan recuperado de los efectos tóxicos clínicamente significativos de estos tratamientos previos. -Todos los hombres con capacidad reproductiva deben aceptar medidas anticonceptivas eficaces durante las 4 semanas anteriores a la entrada en el estudio, durante toda la duración del estudio y durante 2 meses tras el estudio, a menos que su infertilidad esté documentada. -Capacidad de comprender y dispuesto a firmar el formulario de consentimiento informado. |
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E.4 | Principal exclusion criteria |
?AML is of the sub-type of acute promyelocytic leukemia or extramedullary myeloid tumor without bone marrow involvement ?Having received hypomethylating agents or other anti-cancer agents administered orally, intravenously or subcutaneously for MDS or MPD that preceded the AML; hydroxyurea used to control peripheral white blood cells count (WBC) or thrombocytosis and lenalidomide used to treat transfusion-dependent anemia are not considered anti-cancer therapy ?Patients with suspected or known central nervous system (CNS) involvement by leukemia should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events ?Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active cancer(s) other than AML, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients receiving intravenous antibiotics for infections that are under control may be included in this study. Active cancer other than AML refers to cancer that requires systemic chemotherapy or biological therapy within 6 months of the study entry. Patients who have received only hormonal therapy in the neoadjuvant or adjuvant setting in the past 6 months may participate in this study ?Known hypersensitivity to decitabine ?Known to be HIV-positive |
-La LMA es del subtipo de leucemia promielocítica aguda o tumor mieloide extramedular sin implicación de la médula ósea. -Que hayan recibido agentes hipometilantes u otros agentes anticancerígenos administrados por vía oral, intravenosa o subcutánea para SMD o NMP previos a la LMA; la hidroxiurea utilizada para controlar el recuento de glóbulos blancos (GB) en sangre periférica o la trombocitosis y lenalidomida para tratar la anemia dependiente de transfusiones no se consideran terapias anticancerígenas. -Los pacientes con afectación, presunta o conocida, del sistema nervioso central (SNC) a causa de la leucemia deben excluirse de este estudio clínico, debido a su mal pronóstico y a que a menudo desarrollan una disfunción neurológica progresiva que podría confundir la evaluación de las enfermedades neurológicas y otros acontecimientos adversos. -Enfermedad intercurrente no controlada, incluyendo, aunque sin limitarse a ello, infección en curso o activa, cánceres activos distintos de LMA, insuficiencia cardíaca congestiva sintomática, angina de pecho inestable, arritmia cardiaca o enfermedad psiquiátrica/situación social, que limitarían el cumplimiento de los requisitos del estudio. Los pacientes que reciban antibióticos por vía intravenosa para infecciones que están bajo control pueden incluirse en este estudio. Cáncer activo distinto de la LMA se refiere al cáncer que requiere quimioterapia sistémica o terapia biológica en el plazo de 6 meses desde la entrada en el estudio. Los pacientes que hayan recibido solo terapia hormonal en el tratamiento neoadyuvante o adyuvante en los últimos 6 meses, pueden participar en este estudio. -Hipersensibilidad conocida a la decitabina. -Positivo para VIH. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is overall survival. |
El criterio de valoración de eficacia principal es la supervivencia global |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Final analysis will occur at approximately 424 deaths. |
El analisis final se producirá a 424 muertes aproximadamente. |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are the response rate of CR, CRp, PR, HI, SD and their corresponding durations, transfusion requirements, number of hospitalized days, and 1-year survival. |
Los criterios de valoración de eficacia secundarios son la tasa de respuesta de RC, RCp, RP, MH, EE y sus correspondientes duraciones, los requisitos de transfusión, el número de días de hospitalización y la supervivencia a 1 año. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Final analysis will occur at approximately 424 deaths. |
El analisis final se producirá a 424 muertes aproximadamente. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Ireland |
Italy |
Austria |
Netherlands |
Sweden |
Germany |
Spain |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial 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
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Final analysis will occur at approximately 424 deaths; there might be an extention study for those subjects deriving clinical benefit. |
El análisis final se producirá en aproximadamente 424 muertes; puede haber un estudio de extensión para aquellos sujetos que deriven beneficio clínico. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |