Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

NCT ID: NCT04727827

Last Updated: 2023-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-01
• Study Completion Date: 2023-06-09

Brief Summary

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.

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.

Conditions

Hematopoietic Cell Transplantation; Oncology

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Pharmacogenomic Testing

A pharmacogenomic (PGx) panel will be performed to test for genetic variations in genes related to drug response.

Group Type: EXPERIMENTAL

Pharmacogenomic-guided supportive care

Intervention Type: OTHER

Patients undergoing hematopoietic stem cell transplantation will be genotyped and supportive care therapies tailored to identified drug-gene pairs and guideline recommendations

Interventions

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

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Justin R Arnall, PharmD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Levine Cancer Institute

Charlotte, North Carolina, United States

Countries

United States

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Provided Documents

Document Type: Informed Consent Form

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Other Identifiers

LCI-HEM-BMT-IMPPACT-001

Identifier Type: -

Identifier Source: org_study_id