A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease|
- Response to Treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]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
- Complete Response to Treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Plasma levels of Alpha-1-Antitrypsin(AAT)will be measured before, during and after AAT treatment for steroid refractory GvHD.
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment arm
Alpha-1-Antitrypsin (AAT) for the treatment of Steroid Refractory Acute Graft vs Host Disease.
Drug: Alpha-1-Antitrypsin (AAT)
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.
Other Name: Zemaira
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700036
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|University of Michigan Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Pavan Reddy, MD||University of Michigan Cancer Center|