Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hematopoietic Cell Transplantation, Oncology

Intervention / Treatment
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* Other: Pharmacogenomic-guided supportive care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: This will be a prospective, pre/post interventional, single arm study
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacogenomic, precision medicine, pharmacy practice, bone marrow transplantation