A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease
Condition: Graft vs Host Disease
MeSH terms: Alpha 1-Antitrypsin Deficiency; Graft vs Host Disease
Intervention: Alpha-1-Antitrypsin (AAT)
Intervention description: AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28. A second course of treatment will not be given.
Intervention MeSH terms: Alpha 1-Antitrypsin; Protein C Inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This clinical trial will study the safety and efficacy of using the drug Zemaira, an Alpha
      1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the
      treatment of steroid refractory GVHD.

      For bone marrow transplant patients, the most common, serious complication is Graft vs Host
      Disease (GVHD), which at its most severe is a life-threatening, complication and a
      significant cause of treatment related death, following stem cell transplantation. GVHD is a
      major obstacle to the overall success of transplant treatment, a strategy that would
      otherwise provide the possibility of a cure for patients with blood cancers or severe blood
      disorders. GVHD primarily affects the skin, gut, and liver of the recipient, and involves the
      interaction of the recipient's (the host's) cells and tissues with the donor's immune system
      cells that see the host tissues as foreign, and attack the host's cells resulting in tissue
      and organ damage.

      The severity of acute GvHD ranges from mild to severe, and for patients who don't respond to
      steroid therapy, the complication is nearly always fatal, either from organ damage or
      opportunistic infection as a consequence of high dose, steroid treatments.

      There is currently no known effective therapy for patients with acute graft vs host disease
      that's refractory (nonresponsive) to steroid therapy. As stated earlier,the overwhelming
      majority of these patients may ultimately die from infection. The incidence of acute GvHD
      that requires intervention, is higher for unrelated donor transplants, the most common
      treatment option available, and therefore, these patients are at higher risk for treatment
      related complications from GVHD. Approximately 20,000 unrelated donor transplants are
      performed each year. The magnitude of this problem then is significant for patients who
      otherwise might be cured of their blood cancer or disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age >18 years

          -  Patients must have clinical evidence* of steroid-refractory acute Graft vs Host
             Disease (any organ) defined as one of the following:

               -  No change or progression in the stage of skin GvHD after at least 1 week of
                  2mg/kg/day methylprednisolone (or po equivalent)

               -  lack of response of visceral (liver, GI) GvHD despite treatment with 2mg/kg/day
                  methylprednisolone for at least 72h.

               -  progression of visceral GvHD despite treatment with 2mg/kg/day methylprednisolone
                  for at least 48h

               -  visceral GvHD progressing to stage 4 after 24h of 2mg/kg/d methylprednisolone

               -  Patients with protracted acute GvHD who have not responded to at least 0.5mg/kg/d
                  of prednisone are considered eligible.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  * As GvHD is a clinical diagnosis, and patients will have already been initiated on
             steroid therapy at the discretion of the attending physician, tissue confirmation of
             refractory GvHD by biopsy is not required for entry to this study. It is anticipated
             that most, but not all, patients will have undergone tissue confirmation of the
             initial diagnosis of GvHD; however lack of tissue confirmation for this clinical
             syndrome is not exclusionary.

        Exclusion Criteria:

          -  As patients with steroid refractory acute GvHD are quite ill with multiple abnormal
             labs and organ dysfunction, there are no explicit laboratory values or degree of organ
             dysfunction that specifically preclude enrollment on this study. Baseline lab studies
             will be obtained and followed throughout this trial as the standard of care for
             patients with GvHD.

          -  Pregnancy or Nursing Mother

          -  Vasopressor requirement

          -  Patients may not be receiving any other investigational agents for the treatment of
             GvHD at time of study entry or at any time while on study or be on another
             investigational agent that can impact on the primary clinical outcome analyses or has
             known pharmacodynamics or pharmacokinetic effects on AAT.

          -  Patients with known antibodies to IgA