Initial Systemic Treatment of Acute GVHD: A Phase II Randomized Trial Evaluating Etanercept, Mycophenolate Mofetil (MMF), Denileukin Diftitox (ONTAK), and Pentostatin in Combination With Corticosteroids (BMT CTN #0302)
BACKGROUND:
Acute graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic
stem cell (HSC) transplantation. Acute GVHD produces significant morbidity and complicates
patient management resulting in organ toxicity, frequent infections, malnutrition, and
substantial delay in recovery from transplantation. Corticosteroids have been the primary
therapy for acute GVHD for over three decades. Various additional immunosuppressive
strategies have been tested as GVHD therapy but neither anti-thymocyte globulin (ATG),
CD5-immunotoxins, IL-1 antagonists nor other agents have been demonstrably helpful in either
control of GVHD symptoms or improvement in survival. Published response rates of complete
response (CR) to acute GVHD therapy with corticosteroids range from 25-41%. These rates
will be used as benchmarks for assessing efficacy of promising new agents. New
immunosuppressive agents and strategies are required to improve the management of GVHD and
decrease the toxicities of the immunosuppressive regimens.
DESIGN NARRATIVE:
In this trial, patients with newly diagnosed acute GVHD will be randomly assigned to receive
corticosteroids plus one of four new agents (etanercept, MMF, denileukin diftitox [Ontak],
and pentostatin). A control arm of only corticosteroids will not be employed. Each agent
will be assessed for safety and efficacy (at least 35% complete remission [CR] rate at Day
28 of therapy can be expected from previously untreated patients).
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Complete Response (CR) at Day 28 of Therapy
Complete response at day 28 after randomization. CR was defined as resolution of all signs and symptoms of Graft-Versus-Host Disease (GVHD) in all evaluable organs in comparison to Day 1 scoring.
Measured at Day 28
No
Edward Ball, MD
Principal Investigator
University of California, San Diego
United States: Food and Drug Administration
285
NCT00224874
September 2005
June 2012
Name | Location |
---|---|
Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
Hackensack University Medical Center | Hackensack, New Jersey 07601 |
City of Hope National Medical Center | Los Angeles, California 91010 |
University of Minnesota | Minneapolis, Minnesota 55455 |
University of Michigan Medical Center | Ann Arbor, Michigan 48104-0914 |
Oregon Health Sciences University | Portland, Oregon |
Texas Transplant Institute | San Antonio, Texas 78229 |
Stanford Hospital and Clinics | Stanford, California 94305 |
University of Florida College of Medicine (Shands) | Gainesville, Florida 32610 |
Johns Hopkins/SKCCC | Baltimore, Maryland 21231 |
Washington University/Barnes Jewish Hospital | St. Louis, Missouri 63110 |
University Hospitals of Cleveland/Case Western | Cleveland, Ohio 44106 |
University of Texas/MD Anderson CRC | Houston, Texas 77030 |
University of California | San Francisco, California 94108 |
DFCI/Brigham & Women's Hospital | Boston, Massachusetts 02114 |
Duke University Medical Center (Peds) | Durham, North Carolina 27705 |