A Proof of Concept Pilot Trial of Alpha-1-Antitrypsin for Pre-Emption Of Steroid-Refractory Acute GVHD
Condition: Graft-versus-host-disease; GVHD
MeSH terms: Alpha 1-Antitrypsin Deficiency; Graft vs Host Disease
Intervention: Alpha 1-Antitrypsin
Intervention description: AAT will be given either in the hospital or the outpatient clinic two times per week.
Intervention MeSH terms: Alpha 1-Antitrypsin; Protein C Inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Intervention model description: Open label single arm
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Bone marrow transplant (BMT) patients can develop graft-versus-host disease (GVHD), a serious
      and potentially fatal complication. The researchers have developed a blood test to identify
      patients most at risk for developing severe GVHD. Patients who consent to this study will
      have their blood tested up to two times after BMT to determine if they are at high risk for
      severe GVHD. The tests will be performed one week and two weeks after BMT. Patients who are
      high risk will be treated with a drug called alpha-1-antitrypsin (AAT) to see if it prevents
      the development of severe GVHD. Patients will receive 16 doses of AAT through a catheter
      placed into a blood vessel over eight weeks. AAT will be given either in the hospital or the
      outpatient clinic two times per week. Patients will be followed for the development of severe
      GVHD for up to four months from the BMT and will continue to be followed at routine clinic
      visits for up to one year after BMT.
    

Eligibility criteria:

        Inclusion Criteria:

          -  High risk prediction score as determined by the Mount Sinai Acute GVHD International
             Consortium (MAGIC) algorithm at either day 7 or day 14 post Hematopoietic cell
             transplant (HCT).

          -  Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral
             blood, cord blood).

          -  Donor and recipient match each other for at least 7/8 HLA-loci (HLA-A, B, C, and DR)

          -  Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is
             acceptable.

          -  GVHD prophylaxis must include a calcineurin inhibitor combined with methotrexate or
             mycophenolate.

          -  The use of serotherapy to prevent GVHD (e.g., antithymocyte globulin) prior to day 3
             post-HCT is permitted

          -  Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert
             syndrome within 3 days prior to enrollment.

          -  ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days
             prior to enrollment.

          -  Signed and dated written informed consent obtained from patient or legal
             representative.

        Exclusion Criteria:

          -  Patients who develop acute GVHD prior to start of study drug

          -  Patients at very high risk for relapse post HCT as defined by very high disease risk
             index

          -  Patients participating in a clinical trial where prevention of GVHD is the primary
             endpoint

          -  Uncontrolled active infection (i.e., progressive symptoms related to infection despite
             treatment or persistently positive microbiological cultures despite treatment or any
             other evidence of severe sepsis)

          -  Patients who are pregnant

          -  Patients on dialysis within 7 days of enrollment

          -  Patients requiring ventilator support or oxygen supplementation exceeding 40% FiO2
             within 14 days of enrollment.

          -  Patients receiving investigational agent within 30 days of enrollment. However, the
             Principal Investigator (PI) may approve prior use of an investigational agent if the
             agent is not expected to interfere with the safety or the efficacy of
             alpha-1-antitrypsin.

          -  History of allergic reaction to alpha-1-antitrypsin