Alpha 1 Anti-Trypsin (AAT) in Treating Patients With Acute Graft-Versus-Host Disease GVHD)

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of AAT in patients with steroid non-responsive acute
GVHD.

II. Characterize pharmacodynamic effects of AAT on pro-inflammatory cytokines, heparan
sulfate, and the spectrum of peripheral blood T cells.

III. Determine clinical responses of GVHD to AAT in patients with steroid non-responsive
acute GVHD.

OUTLINE: This is a phase I/II dose-escalation study of AAT.

Patients will receive AAT intravenously (IV) on study days 1, 3, 5, and 7. Patients who
experience no toxicity and in whom GVHD is stable or improved after the day 7 dose can
continue therapy with AAT on days 9, 11, 13 and 15 for a total of 8 doses.

Inclusion Criteria:

- Patients transplanted from related or unrelated, human leukocyte antigen (HLA) matched
or mismatched donors

- Patients transplanted with hematopoietic stem cells from any source

- Patients receiving calcineurin inhibitors as part of graft versus host disease (GVHD)
prophylaxis

- Patients with acute GVHD grades II-IV developing despite GVHD prophylaxis

- Patients who have not shown a satisfactory response to methylprednisolone-equivalent
doses at 2 mg/kg/day, based on adjusted body weight

- Signed and dated informed consent

Exclusion Criteria:

- Patients who have received any systemic agents in addition to steroids for treatment
of GVHD

- Patients unable to give informed consent

- Patients with manifestations of classic chronic GVHD

- Patients with evidence of recurrent malignancy

- Patients with acute/chronic GVHD overlap syndrome

- Patients whose GVHD developed after donor lymphocyte infusion (DLI)

- Patients with severe organ dysfunction, defined as

- On dialysis

- Requiring oxygen (O2) at more than 2 l/min

- Uncontrolled arrhythmia or heart failure

- Veno-occlusive disease (sinusoidal obstruction syndrome)

- Patients with uncontrolled infections