Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Anti-trypsin (AAT). A Phase I/II Study.
N/A
N/A
Both
Graft Versus Host Disease
Trial Information
Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Anti-trypsin (AAT). A Phase I/II Study.
PRIMARY OBJECTIVES:
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.
OUTLINE:
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
infusions.
After completion of study treatment, patients are followed up periodically.
Inclusion Criteria:
- Patients transplanted from related or unrelated, human leukocyte antigen
(HLA)-matched or mismatched donors
- Any source of hematopoietic stem cells is allowed
- Patients may have received any GVHD prophylactic regimen, but developed acute GVHD
grades II-IV
- Patients will have received primary therapy with steroids, but showed progression of
or did not resolve clinical manifestations of GVHD on methylprednisolone doses >=
1mg/kg; criteria and indications for secondary systemic therapy of acute GVHD have
not been systematically defined; according to American Society for Blood and Marrow
Transplantation (ASBMT) guidelines, both severity and duration of manifestations of
GVHD will be taken into consideration when deciding that steroid treatment has not
adequately controlled GVHD; in general, the decision to initiate secondary therapy
will be made sooner for patients with more severe GVHD; for example, secondary
therapy may be indicated after 3 days with progressive manifestations of GVHD, after
1 week with persistent, unimproving grade III GVHD or after 2 weeks with persistent,
unimproving grade II GVHD; secondary systemic therapy may also be indicated earlier
in patients who cannot tolerate high-dose glucocorticoid treatment
Exclusion Criteria:
- Patients who have received agents in addition to steroids for therapy of GVHD
- Unable to give informed consent
- Patients with manifestations of classic chronic GVHD
- Patients with evidence of recurrent malignancy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Achievement of targeted alpha 1 anti-trypsin plasma concentrations
Outcome Description:
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.
Outcome Time Frame:
After dose 1 (24 or 48 hour interval)
Safety Issue:
No
Principal Investigator
H. Joachim Deeg
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Authority:
United States: Federal Government
Study ID:
2571.00
NCT ID:
NCT01523821
Start Date:
February 2013
Completion Date:
Related Keywords:
- Graft Versus Host Disease
- Graft vs Host Disease
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