Alefacept for Prevention of Graft Versus Host Disease (GVHD)
Status:
Terminated
Trial end date:
2013-12-01
Target enrollment:
Participant gender:
Summary
Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein. It was shown to
interfere with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2,
and inhibiting LFA-3/CD2 interaction. Alefacept was evaluated in two randomized,
double-blind, placebo-controlled studies in adults with chronic (>1 year) plaque psoriasis
and a minimum body surface area involvement of 10% who were candidates for or had previously
received systemic therapy or phototherapy. The response to alefacept was significantly better
in both studies. In both studies, onset of response to alefacept treatment (defined as at
least 50% reduction of baseline Psoriasis Area and Severity Index (PASI)) began 60 days after
the start of therapy.
Graft versus host disease (GVHD) is the most ominous side effect of allogeneic stem cell
transplantation (SCT). It causes severe inflammatory process, which is usually located to the
skin, gut and liver. Treatment of GVHD consists of various immuno-suppressive and
immuno-modulating drugs, including steroids, cyclosporine, tacrolimus, methotrexate etc.
These drugs unfortunately can also cause severe immunologic failure that makes the patient
prone to infection and malignancy, and other medication-specific side effects. In spite of
this effect on the immune system, not all of the patients achieve control of GVHD, which
usually rapidly leads to death. Despite the use of innovative immunosuppressive modalities,
the prognosis of steroid resistant GVHD is usually poor.
It was shown that CD2 depletion of allografts could prevent GVHD. Alefacept was never
systemically tried in GVHD but A phase II study of BTI-322, a rat monoclonal IgG2b directed
against the CD2 antigen in steroid-refractory acute GVHD showed a total response rate of 55%.
We showed that alefacept might have a beneficial effect in controlling steroid resistant
aGVHD and chronic GVHD. It was also shown to dramatically change the nature of transfusion
associated GVHD.