A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome (MDS)
Many bone marrow failure syndromes in humans are now recognized to result from immunological
mechanisms. These diseases include aplastic anemia, pure red cell aplasia, and some types of
myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia,
leukopenia, and thrombocytopenia, alone or in combination, have been shown to respond to a
wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CsA)
and horse antithymocyte globulin (h-ATG). However, non-response and relapse continues to be
a problem. Why some patients do not respond initially or others respond and then relapse is
unclear. Autoreactive T cells may be resistant to the effect of h-ATG/CsA (non-responders),
while in others, residual autoreactive T cells expand post-treatment leading to
hematopoietic stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel,
less toxic immunosuppressive regimens that increase response rates and hematologic recovery
and decrease relapse rates are needed.
One such novel therapy, alemtuzumab (Campath[R]) is a humanized IgG1 monoclonal antibody
directed against the CD52 protein, which is highly expressed on all lymphoid cells and
monocytes. Alemtuzumab (Campath[R]), produces profound and persistent lymphopenia,
affecting predominantly the CD4+ T cell subset. This property has made it attractive in the
treatment of a wide range of diseases including rheumatoid arthritis, multiple sclerosis,
ocular inflammatory disease, lymphoid malignancies, organ allograft rejection, and in
conditioning regimens in stem cell transplantation to prevent graft failure and
We therefore propose a non-randomized, off label, pilot, Phase I/II study of alemtuzumab
(Campath) in MDS patients who are likely to respond to immunosuppression.
Primary endpoints will be changes in peripheral blood counts (platelets, absolute neutrophil
count, reticulocyte count, hemoglobin). Secondary endpoints (in transfusion-dependent
patients) include improvement in the transfusion requirements (measured as decrease in the
number of transfusion administered on as needed basis), duration of response, late effects
of treatment, relapse and survival.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Hematologic response (complete or partial) at 3 months after the first dose of alemtuzumab and sustained on greater than or equal to 2 serial measurements performed 1 month apart.
Ronan G Desmond, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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