Three Immunosuppressive Treatment Regimens for Severe Aplastic Anemia
Status:
Completed
Trial end date:
2016-05-04
Target enrollment:
Participant gender:
Summary
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized
by pancytopenia and a hypocellular bone marrow. Allogeneic bone marrow transplantation offers
the opportunity for cure in 70% of patients, but most patients are not suitable candidates
for hematopoietic stem cell transplantation (HSCT) due to advanced age or lack of a
histocompatible donor. For these patients, comparable long term survival is attainable with
immunosuppressive treatment with anti-thymocyte globulin (ATG) and cyclosporine (CsA).
However, of those patients treated with horse ATG(h-ATG)/CsA, one quarter to one third will
not respond, and about 50% of responders relapse. Auto-reactive T cells may be resistant to
the effect of ATG/CsA (non-responders), while in others residual auto-reactive T cells expand
post-treatment, leading to hematopoietic stem cell destruction and recurrent pancytopenia
(relapse). As long term survival is correlated to response rates and robustness of
hematopoietic recovery, novel immunosuppressive regimens that can achieve hematologic
response and decrease relapse rates are needed.
This trial will compare the effectiveness of three immunosuppressive regimens as first line
therapies in patients with SAA with early hematologic response as the primary endpoint, as
well as assess the role of extended CsA treatment after h-ATG in reducing numbers of late
events of relapse and clonal evolution. Randomization is employed to obtain an equal
distribution of subject to each arm; comparisons of early hematologic responses will be made
among the rates observed among the three concurrent arms (rabbit-ATG [r-ATG] versus standard
h-ATG; alemtuzumab vs standard h-ATG). For long course CSA, comparison of primary end points
will be to well established historic relapse rate of 38% at 2-3 years and a cumulative rate
of clonal evolution of 15%.