- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02914327
Safety and Activity of SNX-5422 Plus Ibrutinib in CLL
A Phase 1, Open-label Study of SNX-5422 and Ibrutinib in Chronic Lymphocytic Leukemia Subjects With a Mutation in Bruton's Tyrosine Kinase
Descripción general del estudio
Descripción detallada
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation.
BTK is a critical kinase in the B cell receptor signaling pathway. This pathway is amplified in CLL and results in amplification of proliferation and anti-apoptotic signals. By inhibiting BTK, ibrutinib eliminates the activation of these pro-survival pathways and microenvironment survival signals. While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, which both decrease ibrutinib's affinity for BTK, and also changes the binding from irreversible to reversible. This is a proof of concept study to investigate whether the addition of SNX-5422 to an established dose of ibrutinib will reduce mutated BTK from CLL cells and/or prevents or delays disease progression of subjects with CLL.
This is an open-label study of SNX-5422 combined with ibrutinib. In each 28 day cycle, SNX-5422 will be dosed in the morning once every other day for 21 days, followed by a 7-day drug-free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon every day for 28 days. cycle
Tipo de estudio
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Ohio
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Columbus, Ohio, Estados Unidos, 43210
- Wexner Medical Center, Ohio State University
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Males or non-pregnant, non-breastfeeding females 18 years-of-age or older
- A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib without evidence of disease progression.
- No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
- Presence of mutated BTK in ≥ 4% of peripheral blood or bone marrow CLL cells, or ≥1% and rising on two separate measurements obtained at least 28 days apart.
- Life expectancy of at least 9 months
- Karnofsky performance score 70
- Adequate baseline laboratory assessments
- Signed informed consent form
- Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia
- Subjects with reproductive capability must agree to practice adequate contraception methods.
Exclusion Criteria:
- Subjects experiencing toxicity with ibrutinib
- Prior treatment with any Hsp90 inhibitor.
- Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
- Conventional chemotherapy or radiation within 4 weeks.
- The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
- Screening ECG QTc interval 470 msec for females, 450 msec for males.
- At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
- Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
- Gastrointestinal diseases or conditions that could affect drug absorption
- Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
- History of documented adrenal dysfunction not due to malignancy.
- History of chronic liver disease.
- Active hepatitis A or B.
- Current alcohol dependence or drug abuse.
- Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose
- Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
- Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
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: SNX-5422 plus ibrutinib
Open-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle.
Subjects will repeat the 28-day schedule until the cancer progresses or the subject is unable to tolerate the therapy
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Cápsulas de SNX-5422 dosificadas en días alternos durante 21 días de un ciclo de tratamiento de 28 días hasta una dosis total de 56 mg/m2 de SNX-5422.
Los sujetos se autoadministrarán ibrutinib oral diario por la tarde con al menos 8 horas de diferencia con SNX-5422 durante 28 días de cada ciclo.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Efficacy of the combination of SNX-5422 and ibrutinib
Periodo de tiempo: Every 12 weeks up to 52 weeks
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Change in percent of mutated BTK in CLL cells
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Every 12 weeks up to 52 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Número de sujetos que informaron eventos adversos
Periodo de tiempo: Día 28 de cada ciclo de 4 semanas desde la aleatorización hasta las 52 semanas
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Frecuencia y gravedad de los eventos adversos
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Día 28 de cada ciclo de 4 semanas desde la aleatorización hasta las 52 semanas
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Time to disease progression
Periodo de tiempo: Up to 52 weeks
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Elapsed time for each subject from randomization to relapse of disease up to 52 weeks
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Up to 52 weeks
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Clinical Laboratory testing
Periodo de tiempo: Day 28 of each 4 week cycle from randomization up to 52 weeks
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Absolute values and changes from baseline for each subject using standard clinical chemistry, hematology and urinalysis parameters
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Day 28 of each 4 week cycle from randomization up to 52 weeks
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Electrocardiogram
Periodo de tiempo: Pre-dose on Day 1 of each 4 week cycle from randomization up to 52 weeks
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Digital 12-lead ECG using standard recording methods at trough drug levels.
All ECG recordings will be analyzed for PR, RR, QT intervals, and for morphology.
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Pre-dose on Day 1 of each 4 week cycle from randomization up to 52 weeks
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Colaboradores e Investigadores
Patrocinador
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 (Estimar)
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
Palabras clave
Otros números de identificación del estudio
- SNX-5422-CLN1-011
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (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. .
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