Efficacy and Safety of Nilotinib in CML-CP (ENESTKorea)
A Phase 4 Study of Nilotinib in Korean Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Chronic Phase
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Nilotinib is a second-generation tyrosine kinase inhibitor with improved efficacy compared to imatinib. However, there are still many patients for whom the therapeutic response is inadequate, or toxicity is limiting the treatment. Serum concentration of nilotinib was shown to affect time to response and progression in previous studies. Therefore, the investigators hypothesized that the optimal plasma level of nilotinib that is sufficient to achieve adequate clinical response while not generating major adverse events could be elucidated by the analysis of combined clinical and pharmacokinetic data.
ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily), in adult patients diagnosed as Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in chronic phase (CML-CP). Plasma samples are collected every three months, for up to 12 months, to determine plasma nilotinib concentrations (PNCs). The primary endpoint is the cumulative rate of molecular response 4.5 (MR4.5; BCR-ABL1IS ≤ 0.0032%) by 24 months. Secondary endpoints include the cumulative rates of MR3 (BCR-ABLIS ≤ 0.1%) and MR4 (BCR-ABLIS ≤ 0.01%) by 12 and 24 months; time to MR3, MR4, and MR4.5; progression-free survival (PFS); overall survival (OS). Correlations between PNCs and clinical outcomes are also analyzed.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 4
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Aged 19 or older
- Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase
Exclusion Criteria:
- CML with atypical BCR-ABL1 transcripts (transcripts other than e13a2 or e14a2)
- Eastern Cooperative Oncology Group performance status ≥ 3
- Cardiac abnormality including a corrected QT interval ≥ 480 milliseconds, complete left bundle branch block, permanent pacemaker implantation, congenital long QT syndrome, history of tachyarrhythmia requiring treatment, clinically significant resting bradycardia, history of acute coronary syndrome within 12 months, and decompensated congestive heart failure
- Organ dysfunction defined by total serum bilirubin levels ≥ 1.5 × the upper limit of the normal range (ULN), creatinine ≥ 1.5 × ULN, aspartate or alanine aminotransferase ≥ 2.5 × ULN, amylase or lipase ≥ 1.5 × ULN and alkaline phosphatase ≥ 2.5 × ULN not directly related to the CML
- Uncontrolled hypertension and/or diabetes
- Active and uncontrolled infection
- Major surgery within two weeks or incomplete recovery from the previous surgery
- Congenital or acquired bleeding tendency
- Impaired gastrointestinal absorption
- History of small bowel resection or bypass surgery
- History of acute pancreatitis within 12 months or chronic pancreatitis
- Concomitant administration of strong irreplaceable CYP3A4 inhibitors or inducers, QT-prolonging agents, or coumarin derivatives
- Any other uncontrolled medical conditions that would present substantial safety risks or compromise compliance with the study treatment
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Investigational arm
Oral nilotinib 300mg twice daily with a 12-hour interval
|
Nilotinib 300mg twice-daily
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Cumulative rate of molecular response 4.5 by 24 months
Periodo de tiempo: 24 months
|
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.0032%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
|
24 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Cumulative rate of molecular response 3 by 24 months
Periodo de tiempo: 24 months
|
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.1%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
|
24 months
|
|
Cumulative rate of molecular response 3 by 12 months
Periodo de tiempo: 12 months
|
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.1%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
|
12 months
|
|
Cumulative rate of molecular response 4 by 24 months
Periodo de tiempo: 24 months
|
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.01%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
|
24 months
|
|
Cumulative rate of molecular response 4 by 12 months
Periodo de tiempo: 12 months
|
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.01%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
|
12 months
|
|
Progression-free survival
Periodo de tiempo: 24 months
|
Time from enrollment to documented disease progression or death from any cause
|
24 months
|
|
Overall survival
Periodo de tiempo: 24 months
|
Time from enrollment to death from any cause
|
24 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Inho Kim, MD, Seoul National University Hospital
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 1110-124-383
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .