A Phase II Study of Xcellerated T Cells™ in Patients with Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma (NHL).

Background: T cells can be activated and expanded ex vivo using the Xcellerate™ Process, in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 and anti-CD28 antibody-coated magnetic beads (Xcyte™-Dynabeads®). In an ongoing trial of Xcellerated T Cells in subjects with chronic lymphocytic leukemia, marked and sustained reductions in lymphadenopathy and splenomegaly were observed (Wierda et al., ASCO 2004). Increases in neutrophil, platelet and NK cell counts were also documented. This study is designed to determine if similar effects can be observed in subjects with indolent non-Hodgkin’s lymphoma (NHL).

Methods: Subjects must have indolent NHL (follicular, small lymphocytic, marginal zone, or mantle cell lymphoma), have relapsed or refractory disease, and have received at least 1 but not more than 4 prior treatment regimens. PBMC are collected by leukapheresis for the Xcellerate Process, and subjects subsequently receive two infusions of 20–60 x 10⁹ Xcellerated T Cells separated by 6–8 weeks. Approximately 40 subjects will be treated.

Results: Seven subjects have been enrolled and Xcellerated T Cells have been manufactured in 5 subjects to date. T cells expanded 181.8 ± 88.5 fold and the final product was >99.0 ± 0.0% T cells (mean + SD). One subject with small lymphocytic lymphoma has been treated with two infusions of 38.6 x 10⁹ Xcellerated T Cells. There have been no serious adverse events to date. Following the first treatment, the lymphocyte count increased from 1.8 x 10⁹/L to 2.9 x 10⁹/L on Day 28. The neutrophil count also increased from 2.9 x 10⁹/L to 5.5 x 10⁹/L six weeks following infusion. The subject had a significant reduction in cervical lymphadenopathy and a slight decrease in bulky mesenteric lymphadenopathy six weeks following the first infusion.

Conclusions: Xcellerated T Cells can be manufactured in subjects with indolent NHL. Treatment leads to significant increases in T cell and neutrophil counts. Preliminary data suggest a reduction in peripheral lymphadenopathy. Data on additional subjects will be presented.