Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Anti-trypsin (AAT). A Phase I/II Study.
I. Determine the optimum dosing parameters of AAT (alpha 1 anti-trypsin) in patients with
steroid refractory acute GVHD.
II. Determine clinical toxicity. III. Characterize pharmacodynamic effects of AAT on
pro-inflammatory cytokines, heparan sulfate, and the spectrum of peripheral blood T cells.
Patients receive alpha 1 anti-trypsin intravenously (IV) on days 1, 3, 5, 7, 9, and 11.
Patients not achieving target alpha 1 anti-trypsin concentrations may receive an infusion
every 24 hours. Patients with GVHD after 6 infusions may continue treatment for up to 12
After completion of study treatment, patients are followed up periodically.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Achievement of targeted alpha 1 anti-trypsin plasma concentrations
Alpha 1 anti-trypsin target concentrations indicated are based on pilot data and the intended suppression of pro-inflammatory cytokines by >= 50%. Stool concentrations of AAT will be measured to determine the effect of IV administered AAT on the expected healing of the intestinal mucosa and the loss of AAT in the stool.
After dose 1 (24 or 48 hour interval)
H. Joachim Deeg
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government