Natural History Study to Determine Drug Metabolism Phenotype and Appropriate Germline Source DNA in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant
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.
...
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Christopher G Kanakry, M.D.
- Phone Number: (240) 760-6171
- Email: christopher.kanakry@nih.gov
Study Contact Backup
- Name: Amy Vicens, R.N.
- Phone Number: (240) 921-4889
- Email: amy.vicens@nih.gov
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health Clinical Center
-
Contact:
- NIH Clinical Center Office of Patient Recruitment (OPR)
- Phone Number: TTY dial 711 800-411-1222
- Email: ccopr@nih.gov
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Cohort 1
Participants undergoing allogeneic HSCT and donors
|
Short tandem repeat (STR) analysis from genomic DNA extracted from biospecimens.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic hematopoietic stem cell transplant (HSCT)
Time Frame: 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.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Christopher G Kanakry, M.D., National Cancer Institute (NCI)
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10001796
- 001796-C
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.