Clinical Trial: A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease

Brief 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

Detailed Summary:
Sponsor: University of Michigan Cancer Center

Current Primary Outcome: Response to Treatment [ Time Frame: 4 weeks ]

To estimate the proportion of patients with steroid refractory acute Graft vs Host Disease) GvHD who respond (PR + CR) to Alpha-1 Antitrypsin (AAT) at a dose of 60mg/kg twice weekly for 8 doses


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Complete Response to Treatment [ Time Frame: 4 weeks ]
    To estimate the proportion of patients in complete remission (CR) without additional therapy at four weeks after the last dose of AAT
  • Infection Rates [ Time Frame: 8 weeks ]
    To estimate the incidence of infection during and following treatment of steroid refractory acute GVHD with AAT
  • Six month survival without additional GVHD therapy [ Time Frame: 6 months ]
    survival at 6 months without additional therapy in patients receiving AAT treatment for steroid refractory acute GVHD.
  • Analysis of plasma cytokine levels [ Time Frame: 56 days ]
    Plasma levels of six plasma biomarkers IL2Rα, TNFR1,HGF, IL8, elafin, and reg3α will be measured before, during and after administration of AAT treatment for steroid refractory GvHD.
  • Analysis of plasma levels for Alpha-1-Antitrypsin (AAT) [ Time Frame: 56 days ]
    Plasma levels of Alpha-1-Antitrypsin(AAT)will be measured before, during and after AAT treatment for steroid refractory GvHD.


Original Secondary Outcome:

  • Complete Response to Treatment [ Time Frame: 4 weeks ]
    To estimate the proportion of patients in complete remission (CR) without additional therapy at four weeks after the last dose of AAT
  • Infection Rates [ Time Frame: 8 weeks ]
    To estimate the incidence of infection during and following treatment of steroid refractory acute GVHD with AAT
  • Six month survival without additional GVHD therapy [ Time Frame: 6 months ]
    survival at 6 months without additional therapy in patients receiving AAT treatment for steroid refractory acute GVHD.


Information By: University of Michigan Cancer Center

Dates:
Date Received: October 2, 2012
Date Started: July 2013
Date Completion: June 2019
Last Updated: July 21, 2016
Last Verified: July 2016