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- Ensayo clínico NCT00676728
A Study of the Histone-deacetylase Inhibitor JNJ-26481585 in Patients With Advanced or Refractory Leukemia or Myelodysplastic Syndrome
13 de septiembre de 2012 actualizado por: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
A Phase 1 Study of the Histone-deacetylase Inhibitor JNJ-26481585 in Subjects With Advanced or Refractory Leukemia or Myelodysplastic Syndrome
The purpose of this study is to explore the safety, pharmacokinetic (what the body does to the medication), pharmacodynamic (what the medication does to the body), and activity of JNJ-26481585 in patients with advanced or refractory leukemia and myelodysplastic syndrome (MDS).
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
This is an open-label (all people know the identity of the intervention), Phase 1 dose escalation, 2-part study (Part I and Part II).
In Part I of the study, the Maximum Tolerated Dose (MTD) defined as the highest dose with an observed incidence of dose limiting toxicity (DLT) in no more than 1 in 6 patients, will be determined using rapid escalation (Stage 1) followed by conventional escalation (Stage 2).
In Stage 1, at least 2 patients will be enrolled at each dose level; dose increments of 100% will be applied.
In Stage 2, at least 3 patients will be enrolled at each dose level and dose increments of 20-50% will be implemented.
Decisions on dose escalation or de-escalation, changes in the timing of pharmacokinetic/pharmacodynamic sampling, and the exploration of an alternative schedule were to be made by the Study Evaluation Team (SET), which consisted of all principal investigators, the medical monitor, and 1 of the sponsor's clinical pharmacologists.
Part II of the study will be the expansion phase, which will begin after the MTD had been determined in Part I and an additional cohort of patients with MDS will be enrolled to further explore the safety and activity of JNJ 26481585 in patients with MDS.
The starting dose for patients enrolled in Part II of the study was to be the MTD established in Part I. Depending on the outcome, the SET may decide to continue at the MTD dose, or dose-de-escalate to the next lower level (25 50% decrement from MTD).
The cohort for MDS will be expanded to consist of 16 evaluable patients.
Safety will be evaluated throughout the study and will include evaluations of adverse events clinical laboratory tests, electrocardiogram (ECG), vital signs, 24 hours Holter ECG, physical examination, Eastern Cooperative Oncology Group performance status and Multiple Gated Acquisition scan or echocardiography.
Tipo de estudio
Intervencionista
Inscripción (Actual)
10
Fase
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Maryland
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Baltimore, Maryland, Estados Unidos
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Texas
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Houston, Texas, Estados Unidos
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Histologically or cytologically confirmed advanced or refractory acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia in blast phase, refractory chronic lymphocytic leukemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia
- For Part II, patients with myelodysplastic syndrome
- Eastern Cooperative Oncology Group Performance Status Score 0, 1 or 2
- Left Ventricular Ejection Fraction greater than or equal to 50%
- Negative hepatitis B, C and human immunodeficiency virus (HIV) test within last 3 months
- Adequate liver and kidney function
Exclusion Criteria:
- Known or suspected involvement of the central nervous system
- Chemotherapy (nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy or treatment with investigative agent within 3 weeks before study drug administration (except hydroxyurea which should be stopped at least 24 hours prior to first dose)
- Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure
- Poorly controlled hypertension or diabetes, ongoing active infection and psychiatric illness
- Receiving medications known to have a risk of causing QTc prolongation
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿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 |
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Experimental: JNJ-26481585
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In Part 1, Initial dose of JNJ-26481585 4 mg oral capsule is administered once daily on each day of a 21-day cycle.
Dose will be escalated or de-escalated until Maximum tolerated dose (MTD) of JNJ-26481585 is determined in Part 1. MTD of JNJ-26481585 will be the initial dose in Part 2.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of patients with adverse events
Periodo de tiempo: Upto 14 days after last dose administration of study medication
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Upto 14 days after last dose administration of study medication
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Number of patients with dose limiting toxicity [DLT]
Periodo de tiempo: From the date of dosing upto 3 months after the date the last patient enrolled in Part I of the study, received the first dose of study medication
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Only toxicities that occur during Treatment Cycle 1 will be used for the purposes of defining DLT.
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From the date of dosing upto 3 months after the date the last patient enrolled in Part I of the study, received the first dose of study medication
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Maximum tolerated dose (MTD) of JNJ 26481585
Periodo de tiempo: From the date of dosing upto 3 months after the date the last patient enrolled in Part I of the study, received the first dose of study medication
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The MTD is defined as the highest dose with an observed incidence of DLT in no more than 1 in 6 patients.
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From the date of dosing upto 3 months after the date the last patient enrolled in Part I of the study, received the first dose of study medication
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Maximum plasma concentration (Cmax) of JNJ 26481585
Periodo de tiempo: Days 1, 2, 8, 15 and 21 of Cycle 1
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Days 1, 2, 8, 15 and 21 of Cycle 1
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Time to reach maximum plasma concentration (tmax) of JNJ-26481585
Periodo de tiempo: Days 1, 2, 8, 15 and 21 of Cycle 1
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Days 1, 2, 8, 15 and 21 of Cycle 1
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Area under the plasma concentration-time curve from time 0 to 24 hours (AUC0-24)
Periodo de tiempo: Days 1, 2, 8, 15 and 21 of Cycle 1
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Days 1, 2, 8, 15 and 21 of Cycle 1
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Elimination half-life (t1/2) of JNJ-26481585
Periodo de tiempo: Days 1, 2, 8, 15 and 21 of Cycle 1
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Days 1, 2, 8, 15 and 21 of Cycle 1
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Cumulative amount of drug excreted in urine over 24 hours (Ae24)
Periodo de tiempo: Days 1 and 21 of Cycle 1
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Days 1 and 21 of Cycle 1
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Renal clearance (CLR) of JNJ 26395018
Periodo de tiempo: Days 1 and 21 of Cycle 1
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Days 1 and 21 of Cycle 1
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Concentration of biomarker histone acetylation
Periodo de tiempo: Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20
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Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20
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Concentration of biomarker interleukin-6 (IL-6)
Periodo de tiempo: Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20
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Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20
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Concentration of biomarker heat shock protein 90 (Hsp90)
Periodo de tiempo: Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20
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Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20
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Complete Blood Count (CBC)
Periodo de tiempo: Pre-treatment (within 4 weeks prior to first dose of JNJ-26481585); Days 1, 3, 8, 15 and 21 of Cycle 1; Days 8, 15 and 21 of Cycle 2; Day 21 of Cycle 3 to 20; follow up (within 14 days after last dose of JNJ-26481585)
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Anticancer activity of JNJ-26481585 explored by assessment of response parameters such as CBC.
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Pre-treatment (within 4 weeks prior to first dose of JNJ-26481585); Days 1, 3, 8, 15 and 21 of Cycle 1; Days 8, 15 and 21 of Cycle 2; Day 21 of Cycle 3 to 20; follow up (within 14 days after last dose of JNJ-26481585)
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Assessment of Transfusion Record
Periodo de tiempo: From Day 1 of Cycle 1 upto 14 days after last dose
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Assessment of Transfusion Record is the parameter for assessment of response.
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From Day 1 of Cycle 1 upto 14 days after last dose
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Radiological Tumor Mass assessment
Periodo de tiempo: Pre-treatment, Day 21 of Cycle 2 to 20 and follow up
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Radiological Tumor Mass assessment is the parameter for assessment of response.
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Pre-treatment, Day 21 of Cycle 2 to 20 and follow up
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Bone marrow aspirate/biopsy assessment
Periodo de tiempo: Pre-treatment, Day 21 of Cycles 1 to 20
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Bone marrow aspirate/biopsy assessment is the parameter for assessment of response.
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Pre-treatment, Day 21 of Cycles 1 to 20
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de diciembre de 2008
Finalización primaria (Actual)
1 de septiembre de 2011
Finalización del estudio (Actual)
1 de septiembre de 2011
Fechas de registro del estudio
Enviado por primera vez
8 de mayo de 2008
Primero enviado que cumplió con los criterios de control de calidad
12 de mayo de 2008
Publicado por primera vez (Estimar)
13 de mayo de 2008
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
14 de septiembre de 2012
Última actualización enviada que cumplió con los criterios de control de calidad
13 de septiembre de 2012
Última verificación
1 de septiembre de 2012
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CR013960
- 26481585CAN1003 (Otro identificador: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)
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. .
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