Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation (IMPPACT)

July 31, 2023 updated by: Wake Forest University Health Sciences

A Prospective Interventional Trial of Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) is the only curative treatment modality for many hematologic malignancies. Morbidity and mortality rates have declined drastically over the years, secondary to improvements in both transplant techniques and pharmacotherapies, including immunosuppressants, anti-infectives, analgesics and other supportive care medications. Despite advances in patient care, toxicities associated with HCT (e.g., graft-versus-host disease (GVHD), infection, pain, anxiety, depression, mucositis, nausea/vomiting) continue to pose challenges in patient care and have a significant impact on quality of life. (QOL). A recent study demonstrated subjects randomized to intensive supportive care had a clinically significant improvement in their QOL during hospitalization and up to 3 months post-transplant compared to those receiving standard care.

Further follow up evaluations have evaluated the impact of focused palliative care/symptom management on QOL metrics - inclusive of Edmonton Symptom Assessment surveys (ESAS). In other malignant settings, i.e. solid tumor, ESAS has been noted as an effective measure of symptoms control and the utilization of this assessment is linked to positive outcomes. The American Society of Clinical Oncology (ASCO) has designated QOL as the second most relevant metric for post-transplant patient care behind survival, making the optimization of supportive care pharmacotherapy a clinically relevant subject to investigate. Pharmacogenetics (PGx) uses an individual's genetic factors, such as single nucleotide polymorphisms (SNPs), to personalize therapy or dose selection. SNPs encode drug-metabolizing enzymes, transporters, and targets that can significantly impact drug efficacy and toxicity. With the growing complexity of both antineoplastics and supportive care, oncologists have less time to manage each subject's myriad of supportive care concerns by trial and error. Suboptimal management of symptoms compromises potential benefits from cancer therapy, disrupts clinic workflow, increases emergency room visits, and affects both patient satisfaction and reimbursement. Genetic variation is well documented across the human genome and affects a subject's response to medications regarding efficacy and toxicity. The genome is quickly becoming a pragmatic tool that can assist oncologists and other providers in optimizing supportive care for subjects with cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators hypothesize that the implementation of a pharmacist-driven precision medicine service guided by HCT clinical pharmacists and Specialty Pharmacy pharmacists using preemptive pharmacogenomic (PGx) testing will identify drug-gene interactions relevant to the supportive care of HCT subjects. This approach to care may improve symptom management and QOL as interpreted via ESAS in adult HCT subjects treated at our institution. With the experience of past studies and a customized genetic panel, the investigators will genotype subjects prior to transplant and identify actionable drug-gene pairs and utilize these to direct supportive therapies. To date no studies have highlighted the significance of incorporating preemptive PGx testing to personalize therapy selection and dosing into the management of adult HCT subjects as a means of improving QOL and symptom management. The primary aim is to estimate the frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification based on their test results during the study period (from admission for HCT to HCT D100). Secondarily the investigators will measure improvement in aggregate and individual scores on the ESAS survey and will further use the ESAS in its totality to assess the impact of PGx-guided care as compared to pre-implementation/non-PGx driven strategies through aggregate ESAS scores, individual ESAS scores, and differences between HCT admission (or baseline) and HCT Day 30 scores before and after the intervening program. In the outpatient setting the investigators will utilize planned medication reconciliation (with PGx guidance) by Specialty Pharmacy Service pharmacists to adhere to PGx-recommendations and capture insight into the implementation of this program to share with other practitioners. The implementation of this study will personalize pharmacotherapy, improve symptom management and QOL in adult HCT subjects treated at our institution, and offer guidance globally in supporting the role of the pharmacist in pharmacogenomics (PGx) and management of HCT subjects.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • United States
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information
  • Age ≥ 18 years at the time of consent
  • Scheduled HCT (allogeneic and autologous, any conditioning regimen) treatment for any malignant or non-malignant indications (i.e. aplastic anemia)
  • Ability to read and understand English or Spanish
  • Able to provide a buccal sample for DNA extraction and genotyping

Exclusion Criteria:

  • Psychiatric illness/social situations, or active/recent (within 30 days) history of elicit substance abuse that would limit compliance with study requirements as determined by the investigator

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

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pharmacogenomic Testing
A pharmacogenomic (PGx) panel will be performed to test for genetic variations in genes related to drug response.
Other: Pharmacogenomic-guided supportive care
Patients undergoing hematopoietic stem cell transplantation will be genotyped and supportive care therapies tailored to identified drug-gene pairs and guideline recommendations

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification.
Time Frame: from admission for HCT to HCT Day +100
The primary objective is to estimate the frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification based on their test results during the study period
from admission for HCT to HCT Day +100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvements in symptoms from PGx-guided supportive care
Time Frame: HCT admission
Determine if PGx-guided supportive care is associated with changes in symptom management following HCT compared to control data attained from subjects not consenting to PGx testing, as assessed by individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as well as their changes in ESAS scores (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)
HCT admission
Improvements in symptoms from PGx-guided supportive care
Time Frame: HCT Day +30
Determine if PGx-guided supportive care is associated with changes in symptom management following HCT compared to control data attained from subjects not consenting to PGx testing, as assessed by individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as well as their changes in ESAS scores (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)
HCT Day +30
Longitudinal symptoms measurements with PGx-guided supportive care
Time Frame: From baseline to Day +30, Day +60 and Day +100 in those who enroll to the study
Describe longitudinal changes in individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as indicative of QOL (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)
From baseline to Day +30, Day +60 and Day +100 in those who enroll to the study
Determine the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification
Time Frame: From baseline to Day +30 in those who enroll to the study
Among the PGx-guided supportive care subjects, investigators will assess the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification based on PGx results
From baseline to Day +30 in those who enroll to the study
Determine the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification
Time Frame: From baseline to Day +60 in those who enroll to the study
Among the PGx-guided supportive care subjects, investigators will assess the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification based on PGx results
From baseline to Day +60 in those who enroll to the study
Determine the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification
Time Frame: From baseline to Day +100 in those who enroll to the study
Among the PGx-guided supportive care subjects, investigators will assess the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification based on PGx results
From baseline to Day +100 in those who enroll to the study

Collaborators and Investigators

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

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Justin R Arnall, PharmD, Wake Forest University Health Sciences

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)

February 1, 2021

Primary Completion (Actual)

June 9, 2023

Study Completion (Actual)

June 9, 2023

Study Registration Dates

First Submitted

January 18, 2021

First Submitted That Met QC Criteria

January 26, 2021

First Posted (Actual)

January 27, 2021

Study Record Updates

Last Update Posted (Actual)

August 3, 2023

Last Update Submitted That Met QC Criteria

July 31, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCI-HEM-BMT-IMPPACT-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

All data and records generated during this study will be kept confidential in accordance with Institutional policies on subject privacy and HIPAA and that the investigator and other site personnel will not use such data and records for any purpose other than conducting the study. We do not anticipate any breach of confidentiality as no records will be shared with any personnel outside the research team. All medical information will be recorded and stored in a database. The database will exist on a password protected secured server. Medical records data will be abstracted by the Research Designee. All records will be kept confidential.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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