Trial in Progress: Patient-Reported Outcome Measures in the Prospective Observational Cohort Study of Patients at Risk for Chronic Graft-Versus-Host Disease in the United States (THRIVE)

Abstract

Background and Significance: Allogeneic hematopoietic cell transplantation (alloHCT) is a curative immunotherapy for patients with hematologic disorders. However, graft-versus-host-disease (GVHD) is a major limitation to the success of alloHCT, with chronic GVHD (cGVHD) as the leading cause of morbidity and mortality. The pleomorphic nature of cGVHD makes the diagnosis and patient management challenging for clinicians; thus, patient-reported symptoms often guide in diagnosing and determining the severity of cGVHD. Our current understanding of cGVHD is largely based on data from registries, single-institution prospective studies, and the cGVHD Consortium with representation from tertiary care academic centers. Prospective studies including patient-reported outcomes and a focus on a more representative and generalizable sample of patients with cGVHD are needed to better understand cGVHD symptoms, disease burden, and practice patterns for management. This trial in progress focuses on broad patient-centered assessment of post-alloHCT medical and psychosocial complications and patient-reported caregiver involvement in a diverse and contemporary patient population. This study uses multiple organ- or system-directed patient-reported outcome measures (PROMs) to help identify cGVHD symptoms, severity, and impact on patient quality of life including financial impact. The primary objective of THRIVE is to assess the clinical course and burden of cGVHD, including diagnosis and severity recorded in electronic case report forms (eCRFs) and PROMs. Secondary objectives include measuring healthcare resource utilization and patient economic and employment impact associated with cGVHD management, as well as patient-reported organ-specific symptoms. Study Design and Methods: THRIVE is a prospective, longitudinal, observational study (NCT05919511) of alloHCT recipients in the United States that uses a hybrid model designed to work with HCT centers and a virtual platform. Eligible patients are ≥18 years old, received alloHCT 90-180 days before enrollment, and are able to complete patient-assessment questionnaires provided in their preferred language either alone or with minimal caregiver assistance. Up to 1500 alloHCT recipients will be recruited at HCT sites (with the expectation that ~500 will have cGVHD symptoms at enrollment; ~500 are estimated to develop cGVHD during the course of the study; ~500 are estimated not to develop cGVHD during the study; Figure). Patients have the option to participate on a virtual platform. Patients will be followed for 36 months from date of enrollment or until the earliest of study termination, withdrawal, or death. Data from 13 PROMs (Table) divided into 3 groups will be collected every 3 months using a decentralized virtual platform. To reduce survey burden, patients will be randomized into 1 of 6 sequence groups to capture 4-5 PROMs per month in year 1 and every 2 months in years 2 and 3. Clinical data, including medications and adverse events, will be collected and abstracted into eCRFs every 3 months. In general, reporting of results will be descriptive for variables of interest. Summary statistics for continuous variables and for categorical variables will be calculated for all patients as well as for subgroups of interest. Whenever applicable, 95% confidence intervals will be calculated for endpoint estimates. Univariate, multivariate, or repeated-measurement analyses will be performed to assess factors associated with evolution of clinical manifestations of and complications from cGVHD. Recruitment for this study is ongoing.