Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant (HCT)

October 16, 2023 updated by: UNC Lineberger Comprehensive Cancer Center

Development of a Population Pharmacokinetic Model to Optimize Tacrolimus Dosing in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplant.

The purpose of this research study is to evaluate tacrolimus plasma concentrations in patients who will undergo an allogeneic hematopoietic stem cell transplant (HCT). The study aims to identify associations between plasma concentrations, baseline demographic characteristics, clinical lab parameters, and genetic factors. These associations will help clinicians determine the best starting dose for tacrolimus in order to minimize risks of aGVHD and tacrolimus-induced toxicities.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study aims to evaluate tacrolimus concentration-time data to characterize tacrolimus inter-individual pharmacokinetic (PK) variability in adult patients who will receive HCT, and to associate concentration-time data, exposure and clearance data with important clinical endpoints such as acute graft-versus-host disease (aGVHD) and tacrolimus-induced toxicities. This study proposes to enroll 50 patients at University of North Carolina Medical Center (UNCMC) who will undergo allogeneic HCT, who will receive tacrolimus starting the third day prior to allogeneic HCT (Day -3) for aGVHD prophylaxis. This will be an observational study, and its goal will be to ideally collect baseline clinical and demographic data, concentration-time data for tacrolimus on Day -3 (3 days before the transplant), Day -2 (2 days before the transplant), Day -1 (one day before the transplant), and Day 0 (the day of the allogeneic HCT) for a full pharmacokinetic profile. A medical chart review will be conducted to extract data on tacrolimus-induced toxicities (i.e., acute kidney injury [AKI], hypertension, metabolic panel changes, etc.) and aGVHD incidence rate up to Day +100 (100 days post-allogeneic HCT). Blood will also be collected for genotyping and will also be collected after the transplant to obtain information for surrogate PD biomarkers of tacrolimus efficacy, such as interleukin 2 (IL2) production and quantifiable nuclear localization of the dephosphorylated nuclear-activated T cells (NFAT). These data will aid in the development of a population-based PK/pharmacodynamic (PD) model that will serve as the foundation for a proposed precision dosing approach to optimize tacrolimus dosing. One of the secondary endpoints will be time to aGVHD, which will be defined as the duration from D0 until the first occurrence of aGVHD, censored at 100 days post-allogeneic HCT (Day +100). In the case of haplo-transplant patients, they will receive tacrolimus starting on Day +5 (as opposed to on Day -3 in non-haplo-transplant recipients). Per standard of care, haplo-transplant patients are initiated on Day +5 (5 days after the transplant). Therefore, in these patients, serial blood draws will be collected on a similar timeline as the non-haplo-transplant patients, but in this case Day +5, Day +6 (6 days after the transplant), Day +7 (7 days after the transplant), and Day +8 (8 days after the transplant; Day +8 is when they reach steady-state). For the PD biomarker studies in haplo-transplant patients, blood draws will occur on Day +9 (9 days after the transplant), Day +16 (16 days after the transplant), and Day +23 (23 days after the transplant) (Figure 2). All other procedures will remain the same.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Anna DeVane, PharmD
  • Phone Number: 9108745807
  • Email: sdevane@unc.edu

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina at Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This study is a single-center prospective observational study that seeks to characterize steady-state tacrolimus pharmacokinetics pharmacodynamics in adult recipients of their first allogeneic HCT. Adult subjects who receive prophylactic tacrolimus for aGVHD prevention, and who receive active follow-up surveillance at our institution, are eligible for enrollment. The study population will consist of subjects treated in the Inpatient Bone Marrow Transplant Unit at the University of North Carolina Medical Center. A total of 50 subjects will be enrolled.

Description

Inclusion Criteria:

  1. ≥18 years of age
  2. Patients who will undergo their first HCT
  3. Patients who will start tacrolimus for aGVHD prophylaxis
  4. Patients who have provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information

Exclusion Criteria:

  1. Patients who have cognitive impairments that could affect informed decision-making
  2. Patients who are incarcerated
  3. Patients started on a strong CYP3A4 inhibitor (i.e. posaconazole)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Adult patients of allogeneic hematopoietic HCT
Patients who receive their first allogeneic HCT transplant and who receive tacrolimus for aGVHD prophylaxis per standard of care.
Drug: Tacrolimus
Patients will be enrolled into this group if they receive tacrolimus per standard of care. This is an observational study and no interventions will be made.
Other Names:
  • Prograf

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Tacrolimus clearance
Time Frame: Day +1 of tacrolimus administration to Day +4 of tacrolimus administration
Patient's clearance calculated after the first day on tacrolimus and patient's clearance calculated after 5-6 doses of tacrolimus after they reach steady-state
Day +1 of tacrolimus administration to Day +4 of tacrolimus administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence and severity of aGVHD
Time Frame: Day +21 to Day +100 from HCT
The duration from the day of transplant to the first occurrence of aGVHD, censored at 100 days post-HCT.
Day +21 to Day +100 from HCT
Incidence of tacrolimus-induced toxicities
Time Frame: Day -3 to Day +100 from HCT
The duration from the day of transplant to the first occurrence of tacrolimus-induced toxicities (AKI, hypertension, and metabolic abnormalities)
Day -3 to Day +100 from HCT
Time to aGVHD
Time Frame: Day +21 to Day +100 from HCT
The duration from the day of transplant to the first occurrence of aGVHD, censored at 100 days post-HCT.
Day +21 to Day +100 from HCT
Time to tacrolimus-induced toxicities (AKI, hypertension, metabolic panel abnormalities)
Time Frame: Day -3 to Day +100 from HCT
The duration from the day of transplant to the first occurrence of AKI, hypertension, and metabolic panel abnormalities, censored at 100 days post-HCT.
Day -3 to Day +100 from HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UNC Lineberger Comprehensive Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of North Carolina, Chapel Hill

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel J Crona, PharmD, PhD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 15, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 15, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 18, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 19, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 27, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 17, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LCCC2034
  • IRB 19-3328 (Other Identifier: University of North Carolina at Chapel Hill)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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