Pilot Trial of Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Allogeneic Transplant
This is a prospective pilot trial investigating the use of vorinostat (Merck) to standard
graft versus-host disease (GVHD) prophylaxis after unrelated donor allogeneic hematopoietic
cell transplantation (HCT). A major limitation of the increased utilization of allogeneic
HCT is the inferior outcomes when donors other than HLA-matched siblings are used 1,2.
Compared to matched related donors, recipients of matched unrelated donor transplants are at
a significantly increased risk of death and transplant-related mortality (TRM) 3,4. Acute
GVHD remains a significant contributor to TRM, which develops in approximately 50-70% of
recipients receiving these type of grafts despite standard immunosuppressive prophylaxis
5-8. Thus, novel GVHD prophylaxis strategies which successfully attenuate acute GVHD-related
complications without increasing other causes of TRM or relapse are needed.
The historical experience of day 100 grade 2-4 acute GVHD in 154 comparable patients treated
at the University of Michigan (2005 - 2011) receiving standard GVHD prophylaxis after
unrelated donor allogeneic transplant is 48%. At Washington University, the cumulative
incidence of acute grade 2-4 GVHD in patients following unrelated donor transplant is 62%.
Research data collectively suggests, that reducing lethal acute GVHD should improve
long-term survival for patients undergoing unrelated donor transplant.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
vorinostat, added to tacrolimus and methotrexate treatment regimen
If at least 7 of 12 patients can meet the definition of successful study drug administration (≥ 60% of the planned doses) during the period day-10 through day+30 of the study, the regimen is considered tolerable and safe. If no more than 3 subjects are observed with toxicities CTC grade 4 or higher which are considered probably or definitely related to the drug, the regimen is safe.
Pavan Reddy, MD
University of Michigan Cancer Center
United States: Institutional Review Board
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