Natural History Study to Determine Drug Metabolism Phenotype and Appropriate Germline Source DNA in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant

NCT06856226 | Recruiting

• 2 other identifiers: 10001796001796-C
• Study Type: observational
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

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. ...

Conditions

Leukemia; Lymphoma; Hematologic Malignancy

Keywords

Allogeneic Transplant; Hematopoietic Cell Transplant; Bone Marrow Transplant; peripheral blood transplant; Chimerism

Outcome Measures

Primary Outcomes (1)

• To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic hematopoietic stem cell transplant (HSCT)

  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.

Study Arms (1)

Cohort 1

Participants undergoing allogeneic HSCT and donors

Other: Arm 1

Interventions

Arm 1 OTHER

Short tandem repeat (STR) analysis from genomic DNA extracted from biospecimens.

Cohort 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any gender, any age greater than or equal to 18 years, who will donate or receive an allogeneic HSCT.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia; Lymphoma; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Study Officials

• Christopher G Kanakry, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Vicens, R.N.

CONTACT

(240) 921-4889; amy.vicens@nih.gov

Christopher G Kanakry, M.D.

CONTACT

(240) 760-6171; christopher.kanakry@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2025
• First Posted: March 4, 2025
• Study Start: March 4, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 27, 2026

Record last verified: 2026-05-22

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared after completion of the primary endpoint per the data management sharing plan.
• Access Criteria: Data may be requested by contacting the Principal Investigator.

Locations

US (1)