Alefacept in Patients With Relapsed/Refractory Aplastic Anemia
Status:
Terminated
Trial end date:
2013-04-16
Target enrollment:
Participant gender:
Summary
Aplastic Anemia (AA) is an autoimmune hematologic stem cell disease mediated by activated
T-lymphocytes that leads to pancytopenia. The disease related morbidity and mortality if left
untreated can approach 90%. For over 30 years, anti-thymocyte globulin (ATG) in combination
with cyclosporine (CsA) remains the standard therapy. However, the treatment response with
ATG is at best between 50-60% with a sizeable number of partial responses. Treatment with ATG
is also associated with significant toxicity and high relapse rate that can be as high as
45%. Since the prognosis in refractory and relapsed AA remains poor, there is a need for less
toxic novel immunosuppressive agents that can improve response rates and remission duration
in refractory and relapsed AA.
Alefacept is a human recombinant dimeric fusion protein composed of the terminal portion of
leukocyte functioning antigen-3 (LFA3/CD58) and the Fc portion of human IgG1. It prevents
co-stimulatory signals between antigen presenting cells and memory T cells by competitive
inhibition of CD2 in T cells, induces selective apoptosis of CD4+ and CD8+ memory effector T
cells by interaction between the Fc portion of IgG1 and the FcyIII in NK cells, and possibly
direct ligation of CD2 molecules on T cells that subsequently result in the alteration in T
cell agonist signaling. It has been used successfully in the treatment of other T cell
mediated disorders particularly psoriasis and steroid refractory graft versus host disease
(GVHD) with minimal side effects. In a case of liver transplant associated AA (similar to
transfusion associated AA) which is fatal in most patients, Alefacept induced remission after
patient did not respond to ATG and other immunosuppressants. The investigators hypothesize
that the LFA3-CD2 co-stimulatory pathway play an important role in the immune pathogenesis of
AA and treatment with Alefacept can help treat refractory/relapsed cases of AA.