Abatacept in Immune Checkpoint Inhibitor Myocarditis
Start Date
7/2/2022
Completion Date
4/20/2027
Summary
The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.
Detailed Description
This investigator-initiated randomized trial is being conducted to test whether abatacept, as compared to placebo, is associated with a reduction in MACE among participants who develop myocarditis after treatment with an ICI. Immune checkpoint inhibitors leverage the immune system to treat a wide variety of cancers. Myocarditis is an uncommon immune related adverse event (irAE) secondary to treatment with an ICI. The guideline recommended treatment for ICI myocarditis is cessation of the ICI and administration of corticosteroids. However, despite administration of corticosteroids, the rate of MACE with ICI myocarditis is high. Data from multiple independent international cohorts have shown that the rate of MACE with ICI myocarditis despite administration of corticosteroids ranges from 25-50%.For comparison, the rate of MACE with myocarditis unrelated to an ICI is \<5%. Abatacept is a selective co-stimulation modulator that inhibits T cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking its interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. In animal studies of ICI myocarditis, the administration of abatacept led to a reduction in cardiac immune activation and an increase in survival. In retrospective unpublished clinical data, the administration of abatacept to participants with ICI myocarditis on corticosteroids was associated with a reduction in risk of MACE. There are no prospective studies testing whether abatacept is effective among participants with ICI myocarditis. Therefore, the primary aim of this trial is to test in a randomized double-blind placebo-controlled study whether abatacept, administered concurrently with corticosteroids, is associated with a reduction in MACE among participants with recently diagnosed ICI myocarditis
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Abatacept plus
Placebo
Conditions
Locations
Cedars-Sinai Medical Center
Los Angeles, California 02127
United States
University of California Los Angeles
Los Angeles, California 90095
United States
MedStar Health Research Institute, Georgetown University
Washington D.C., District of Columbia 20010
United States
Moffitt Cancer Center
Tampa, Florida 33612
United States
University of Chicago
Chicago, Illinois 60637
United States
Franciscan Health
Indianapolis, Indiana 46237
United States
University of Kansas Medical Center
Kansas City, Kansas 66160
United States
University of Kentucky
Lexington, Kentucky 40536-0200
United States
Maine Health
Portland, Maine 04102
United States
Johns Hopkins
Baltimore, Maryland 21287
United States
Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02115
United States
Boston Medical Center
Boston, Massachusetts 02118
United States
Brigham and Women's Hospital
Boston, Massachusetts 02215
United States
University of Michigan
Ann Arbor, Michigan 48109
United States
Mayo Clinic
Rochester, Minnesota 55905
United States
Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08901
United States
Columbia University Irving Medical Center
New York, New York 10032
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
University of North Carolina Chapel Hill
Chapel Hill, North Carolina 27599-7075
United States
Cleveland Clinic
Cleveland, Ohio 44195
United States
Lehigh Valley Health Network
Bethlehem, Pennsylvania 18017
United States
University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Allegheny-Singer Research Institution
Pittsburgh, Pennsylvania 15212
United States
University of Texas Southwestern
Dallas, Texas 72535
United States
MD Anderson Cancer Center
Houston, Texas 77030
United States
University of Utah
Salt Lake City, Utah 84132
United States
University of West Virginia
Morgantown, West Virginia 26506
United States
Aurora St Luke's Medical Center
Milwaukee, Wisconsin 53215
United States
University of British Colombia
Vancouver, British Colombia V5Z 1M9
Canada
McMaster University
Hamilton, Ontario L8V 1C3
Canada