Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in T and NK-Cell Lymphomas
The clinical outcome for patients with T-cell non-Hodgkin's lymphoma is significantly
inferior to the outcome of patients with B-cell non-Hodgkin's lymphoma. In most reports less
than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.
The combination of alemtuzumab and EPOCH chemotherapy was evaluated in patients with
chemotherapy naive aggressive T and NK cell lymphoid malignancy. Dose-limiting bone marrow
toxicity prevented escalation of the alemtuzumab dose.
Siplizumab is a humanized monoclonal antibody directed at CD2 that demonstrated activity in
the treatment of relapsed/refractory T cell lymphoma, suggesting further development by
combining with chemotherapy for untreated patients. Siplizumab caused EBV
lymphoproliferative disease in patients treated with a weekly schedule of administration.
Rituximab prevents the development of EBV lymphoproliferative disease in the allogeneic
transplant setting and may be active in preventing EBV-related B cell lymphoma in other
Determine the toxicity of siplizumab and dose-adjusted EPOCH rituximab chemotherapy in
chemotherapy naive CD2-expressing T and NK lymphoid malignancies.
Determine the maximum tolerated dose of siplizumab administered in combination with
dose-adjusted EPOCH rituximab chemotherapy.
CD2-expressing lymphoid malignancy.
Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alkpositive
anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.
Four dose levels of siplizumab will be evaluated to determine the toxicity profile and in a
preliminary fashion and its activity in combination with dose-adjusted EPOCH with rituximab.
Four dose levels of siplizumab will be explored, in cohorts of three to six patients each.
Patients will receive 3.4, 4.8, 8.5, or 15 mg/kg of siplizumab on day 1 of therapy, followed
by dose-adjusted EPOCH-rituximab chemotherapy days 1-5 every 3 weeks for a total of 6
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the toxicity of siplizumab and DA-EPOCH-R in chemotherapy na ve CD2-expressing T and NK lymphoid malignancies.Determine the maximum tolerated dose of siplizumab administered in combination with DA-EPOCH-R.
Wyndham H Wilson, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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