title: 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 graft-versus-host disease 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 requiring years of follow-up is urgently needed, 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Electronic address: pmartin@fredhutch.org.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for Drug Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Donna
authors.initials: D
authors.lastname: Przepiorka
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.affiliation: Division of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Georgia B
authors.initials: GB
authors.lastname: Vogelsang
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Irwin
authors.initials: I
authors.lastname: Walker
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Carpenter
authors.affiliation: Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Griffith
authors.affiliation: Stem Cell Transplant Program, Banner MD Anderson Cancer Center, Gilbert, Arizona.
authors.forename: Gorgun
authors.initials: G
authors.lastname: Akpek
authors.affiliation: Clinical Hematology and Cellular Therapy Department, Hôpital Saint-Antoine, University Pierre & Marie Curie, INSERM U938, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Department of Internal Medicine III, University of Regensburg, Regensburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Division of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D049674:History, 21st Century; D006801:Humans; D009316:National Institutes of Health (U.S.); D014481:United States
keywords: Allogeneic hematopoietic cell transplantation; Chronic graft-versus-host disease; Clinical trials; Consensus; Design; Guidelines