Siplizumab, Combination Chemotherapy, and Rituximab in Treating Patients With T-Cell or Natural Killer-Cell Non-Hodgkin Lymphoma

OBJECTIVES:

Primary

- Determine the toxicity of siplizumab in combination with dose-adjusted etoposide,
prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and
rituximab (DA-EPOCH-R) in patients with chemotherapy-naive, CD2-expressing T-cell or
natural killer (NK)-cell non-Hodgkin lymphoma.

- Determine the maximum tolerated dose of siplizumab in combination with DA-EPOCH-R in
these patients.

Secondary

- Determine, preliminarily, the anti-tumor activity of siplizumab and DA-EPOCH-R in these
patients.

- Determine the time course of B-, T-, and NK-cell depletion.

- Determine the time course of B-, T- and NK-cell recovery.

- Monitor EBV reactivation and its association with the development of EBV
lymphoproliferative disease.

OUTLINE: This is a dose-escalation study of siplizumab.

Patients receive siplizumab IV on day 1. Patients also receive dose-adjusted rituximab IV on
day 1; etoposide IV, vincristine sulfate IV, and doxorubicin IV over 96 hours on days 1-4;
cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5.
Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 6 and
continuing until blood counts recover. Treatment repeats every 21 days for up to 6 courses
in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline, during study, and after completion of
study for pharmacokinetic studies via liquid chromatography mass spectrometry/mass
spectrometry and ELIZA assay and for the evaluation of immunogenicity via human
anti-humanized antibody assay.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4
months for 1 year, every 6 months for 3 years, and then annually thereafter.