Estudio de historia natural para determinar el fenotipo del metabolismo del fármaco y el ADN de la fuente germinal apropiada en pacientes sometidos a trasplante alogénico de células madre hematopoyéticas
Background:
After an allogeneic hematopoietic stem cell transplant (HSCT), the donor genome is found in the recipient s circulation and tissues.
Post-HSCT recipients may receive a medication in which the dosing needs to be adjusted based on genetic variation.
While genes in donor genome may influence dosing and administration of some agents, the majority of established gene-drug pairs in pharmacogenetics are related to expression of metabolic or transporting enzymes located in recipients tissues, often the liver.
Determining which genetic variants influence drug disposition in HSCT recipients is complicated by chimerism in samples that are routinely collected for determining genotype. However, chimerism in tissues is poorly studied in this patient population.
Objectives:
To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic HSCT.
Eligibility:
People ages 18 years and older who are enrolled on a clinical trial at the NIH Clinical Center under which they will donate or receive an allogeneic HSCT.
Design:
DNA is collected prior to HSCT and for two years after HSCT.
Blood will be collected and skin fibroblast cell lines will be established prior to HSCT to serve as a reference genome.
Blood, buccal cells, skin, and hair will be monitored for the development of mixed chimerism via detection of short tandem repeats. Liver biopsies will be collected from participants undergoing hepatic surgery.
Pharmacoscan arrays will be conducted to determine which samples are useful for pharmacogenetic testing in participants who receive allogeneic HSCT.
A probe drug cocktail will be administered pre- and post-HSCT to determine if transplantation alters the metabolic phenotype of liver enzymes.
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Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Background:
- After an allogeneic hematopoietic stem cell transplant (HSCT), the donor genome is found in the recipient fs circulation and tissues.
- Post-HSCT recipients may receive a medication in which the dosing needs to be adjusted based on genetic variation.
- While genes in donor genome may influence dosing and administration of some agents, the majority of established gene-drug pairs in pharmacogenetics are related to expression of metabolic or transporting enzymes located in recipients f tissues, often the liver.
- Determining which genetic variants influence drug disposition in HSCT recipients is complicated by chimerism in samples that are routinely collected for determining genotype. However, chimerism in tissues is poorly studied in this patient population.
Primary Objective:
-To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic HSCT.
Eligibility:
- Age >=18 years
- Must be enrolled on a clinical trial at the NIH Clinical Center under which they will donate or receive an allogeneic HSCT
Design:
- DNA is collected prior to HSCT and for two years after HSCT.
- Blood will be collected and skin fibroblast cell lines will be established prior to HSCT to serve as a reference genome.
- Blood, buccal cells, skin, and hair will be monitored for the development of mixed chimerism. Liver biopsies will be collected from participants undergoing hepatic surgery.
- Whole genome sequencing with Aldy analysis will be conducted to determine which samples are useful for pharmacogenetic testing in participants who receive allogeneic HSCT.
- A probe drug cocktail will be administered pre- and post-HSCT to determine if transplantation alters the metabolic phenotype of liver enzymes.
- Up to 88 participants will be enrolled.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Ashley E Carpenter
- Número de teléfono: (240) 760-6009
- Correo electrónico: carpentera@mail.nih.gov
Copia de seguridad de contactos de estudio
- Nombre: Christopher G Kanakry, M.D.
- Número de teléfono: (240) 760-6171
- Correo electrónico: christopher.kanakry@nih.gov
Ubicaciones de estudio
-
-
Maryland
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Bethesda, Maryland, Estados Unidos, 20892
- Reclutamiento
- National Institutes of Health Clinical Center
-
Contacto:
- NIH Clinical Center Office of Patient Recruitment (OPR)
- Número de teléfono: TTY dial 711 800-411-1222
- Correo electrónico: ccopr@nih.gov
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Any gender, any age greater than or equal to 18 years, who will donate or receive an allogeneic HSCT.
Descripción
- INCLUSION CRITERIA:
- Age >=18 years
- Participants must be enrolled on a clinical trial at the NIH Clinical Center (CC) under which they will donate or receive an allogeneic HSCT. The participant and their donor must enroll together to provide a complete set of samples for analysis.
- Ability of subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
- Donors are not allowed to enroll without a recipient
- Prior allogeneic HSCT
- History of psychiatric disorder which may compromise compliance with protocol requirements.
- Pregnant and lactating individuals
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
Cohort 1
Participants undergoing allogeneic HSCT and donors |
Short tandem repeat (STR) analysis from genomic DNA extracted from biospecimens. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic hematopoietic stem cell transplant (HSCT)
Periodo de tiempo: Pharmacoscan array will be performed within 1 month pre-BM donation in donors and within 1 month pre-HSCT and 12 months post-HSCT in recipients.
|
Obtaining genotype for analysis of pharmacogene activity by understanding the degree chimerism in commonly utilized diagnostic samples. |
Pharmacoscan array will be performed within 1 month pre-BM donation in donors and within 1 month pre-HSCT and 12 months post-HSCT in recipients.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Christopher G Kanakry, M.D., National Cancer Institute (NCI)
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 10001796
- 001796-C
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
Marco de tiempo para compartir IPD
Data will be shared after completion of the primary endpoint per the data management sharing plan.
Criterios de acceso compartido de IPD
Data may be requested by contacting the Principal Investigator.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
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.
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