National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report

Abstract

Treatment of chronic GVHD is intended to produce a sustainable benefit by reducing symptom burden, controlling objective manifestations of disease activity, preventing damage and impairment, and improving overall survival without causing disproportionate harms related to the treatment itself. Successful management can control the disease until systemic treatment is no longer needed. The complexity of the disease, the extended duration of follow-up needed to observe disease resolution and withdrawal of immunosuppressive treatment, and the lack of fully developed shorter-term endpoints impede progress in the field. Identification and characterization of primary endpoints demonstrating clinical benefit without the need for years of follow-up is an urgent need, with the understanding that clinical benefit encompasses not only the self-evident benefit of the primary endpoint but also any other associated benefits. This report discusses regulatory considerations, eligibility criteria, the value of controlled trial designs, the merits of proposed primary endpoints, and key considerations elaborated from experience and progress during the past decade. The report concludes by mapping an overall approach that could support and lead to maximally informative clinical trials, especially those that seek to demonstrate clinical benefit along a pathway to regulatory review and approval.

Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease

“…Based on these data, we recommend that for now, the 2014 NIH response measures, clinician-reported responses, and patientreported outcomes be collected in therapeutic trials of chronic GVHD to ensure that relevant data are available once the best algorithm to capture a meaningful objective response is determined. 43 10. Akpek G, Lee SM, Anders V, Vogelsang GB.…”

Content Validity of the Lee Chronic Graft-versus-Host Disease Symptom Scale as Assessed by Cognitive Interviews

“…A recent NIH Consensus Conference proposed a number of tools to standardize diagnosis, scoring, histopathology, biomarker assays, response assessment and conduct of clinical trials. Patient-reported measures are included in these recommendations [3–4]. …”

An endpoint associated with clinical benefit after initial treatment of chronic graft-versus-host disease

“…8 No gold standard has been established as a primary endpoint in trials of treatment of chronic GVHD, and evidence showing the association of any proposed primary endpoint with clinical benefit has not been conclusively demonstrated.…”