E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukemia (AML) |
Leucemia mieloide aguda |
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E.1.1.1 | Medical condition in easily understood language |
An aggressive cancer of the myeloid cells |
Un cáncer agresivo de las celulas mieloides. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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 |
To compare overall survival (OS) between treatment arms |
Comparar la supervivencia global (SG) de los grupos de tratamiento. |
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E.2.2 | Secondary objectives of the trial |
-To compare the composite complete remission (CRc) rate (complete remission [CR] and morphologic CR with incomplete hematologic recovery [CRi]) between treatment arms -To compare event-free survival (EFS) between treatment arms -To evaluate the duration of remission in the 2 treatment arms -To evaluate leukemia-free survival (LFS) in the 2 treatment arms -To evaluate the safety profiles in the 2 treatment arms -To evaluate the time to response in the 2 treatment arms -To evaluate the 30- and 60-day mortality rates in the 2 treatment arms -To evaluate minimal residual disease (MRD) status |
-Comparar la tasa de remisión completa mixta (RCm) (remisión completa [RC] y RC morfológica con recuperación hematológica incompleta [RCi]) entre los grupos de tratamiento. -Comparar la supervivencia sin acontecimientos (SSA) entre los grupos de tratamiento. -Comparar la duración de la remisión en los 2 brazos de tratamiento -Evaluar la supervivencia sin leucemia (SSL) de los 2 grupos de tratamiento. -Evaluar los perfiles de seguridad de los 2 grupos de tratamiento. -Evaluar el tiempo hasta la respuesta de los 2 grupos de tratamiento. -Evaluar las tasas de mortalidad a los 30 y 60 días de los 2 grupos de tratamiento. -Evaluar el estado de la enfermedad mínima residual (EMR). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Ages Eligible for Study: 65 Years and older Genders Eligible for Study: Both Inclusion Criteria: ? Newly diagnosed, previously untreated, cytologically/histologically confirmed de novo or secondary AML according to WHO classification (except for acute promyelocytic leukemia [APL]) ? Intermediate or adverse cytogenetic risk ? Eligible for therapy with either decitabine or azacitidine ? Acceptable hematologic and organ function |
Edad > ó = a 65 años Ambos sexos. -Pacientes con LMA recién diagnosticada, confirmada citológica o histológicamente de novo o secundaria, que no han recibido tratamiento previo, según la clasificación de la OMS (excepto en el caso de la leucemia promielocítica aguda [LPA]). -Riesgo citogenetico intermedio o despaforable. -El paciente es apto para recibir tratamiento con decitabina o azacitidina. -Estado funcional y hematológico aceptable. |
|
E.4 | Principal exclusion criteria |
? AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or t(15;17). ? Patients who are candidates for allogeneic stem cell transplant at the time of enrollment ? Patients with a history of one of the following myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and primary myelofibrosis. ? Received prior treatment with HMA or chemotherapy for antecedent MDS. |
-LMA asociada a cariotipos de riesgo favorable, incluidos inv(16), t(8;21), t(16;16) o t(15;17). -Pacientes candidatos a trasplante alogénico de células madre en el momento de la inscripción. -Pacientes con antecedentes de alguna de las siguientes neoplasias mieloproliferativas: trombocitemia esencial, policitemia vera y mielofibrosis primaria. -Pacientes que anteriormente han recibido tratamiento con HMA o quimioterapia para tratar un SMD precedente. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival |
supervivencia global |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 5 years. |
Hasta aproximadamente 5 años. |
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E.5.2 | Secondary end point(s) |
-Composite complete remission (CR+CRi) CRc rate -Event-free survival (EFS) -Duration of remission -Leukemia-free survival (LFS) -Type, incidence, severity, seriousness, and relatedness of adverse events -Laboratory abnormalities -Time to Complete Remission (CR) or Morphologic complete remission with incomplete blood count recovery (CRi) -Mortality rates at Day 30 and Day 60 post the first study treatment -Minimal residual disease (MRD) status |
-Comparar la tasa de remisión completa mixta (RCm) (remisión completa [RC] y RC morfológica con recuperación hematológica incompleta [RCi]) entre los grupos de tratamiento. -Supervivencia sin acontecimientos (SSA) entre los grupos de tratamiento. -Duración de la remisión -Supervivencia sin leucemia (SSL) de los 2 grupos de tratamiento. -Tipo, incidencia, severidad, gravedad y relación de los acontecimientos adversos. -Valores de laboratorio fuera de rango. -Tiempo para la remisión completa (RC) (remisión completa [RC] y RC morfológica con recuperación hematológica incompleta [RCi]). -Evaluar las tasas de mortalidad a los 30 y 60 días de los 2 grupos de tratamiento. -Evaluar el estado de la enfermedad mínima residual (EMR). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-(CR+CRi) CRc rate: Through 1 month following last dose -EFS: Up to approximately 5 years -Duration of remission: Up to approximately 5 years -LFS: Up to approximately 5 years -Type, incidence, severity, seriousness, and relatedness of adverse events: Through 1 month following last dose -Laboratory abnormalities : Through 1 month following last dose -Time to complete remission : Through 1 month following last dose -Mortality rates at Day 30 and Day 60 post the first study treatment : Day 30 and Day 60 following the first dose -MRD status : Up to approximately 5 years |
(CRCRi) Tasa de CRc: Durante 1 mes siguiente a la última dosis. -SSA: Hasta aproximadamente 5 años. -Duración de la remisión: hasta aproximadamente 5 años -SSL:Hasta aproximadamente 5 años. -Tipo, incidencia, severidad, gravedad y relación de los acontecimientos adversos: Durante 1 mes siguiente a la última dosis. -Valores de laboratorio fuera de rango.Durante 1 mes siguiente a la última dosis. -Tiempo para la remisión completa: Durante 1 mes siguiente a la última dosis. -Mortalidad a los 30 y 60 días tras el primer tratamiento del estudio: Dia 30 y dia 60 tras la primera dosis. -Estado EMR:Hasta aproximadamente 5 años. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Korea, Republic of |
Poland |
Spain |
Taiwan |
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
|
End of trial is defined as the point when all patients have died or discontinued the study, or have been followed for a maximum of 3 years after the last patient enrolled, whichever comes first. |
El Fin del ensayo se define como el momento en el que todos los pacientes han muerto o han discontinuado el estudio, o han sido seguidos por un máximo de 3 años después de la última inclusion del ultimo paciente, cualquiera que se produzca primero. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |