A phase I/II study of Xcellerated T Cells in patients with chronic lymphocytic leukemia.

2511 Background: T cells from CLL pts can be activated & expanded ex vivo using the Xcellerate Process, in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 & anti-CD28 antibody-coated magnetic beads (Xcyte Dynabeads). With this process, anergic T cells from CLL pts can be activated, leading to upregulation of important immune molecules on leukemic B cells & leukemic cell apoptosis (Bonyhadi et al., J. Immunol, in press).,A total of 17 pts with high risk or symptomatic/progressive intermediate-risk disease were divided into 3 cohorts which were treated with increasing Xcellerated T Cell (XTC) doses: 10 x 10(n=3), 30 x 10 (n=3), and 60-100 x 10(n=11).,Prior treatments included chemotherapy ± monoclonal antibody treatment (n=10), investigational vaccine (n=3), steroids (n=1), and no prior therapy (n=3). There was one serious adverse event (SAE) of atrial fibrillation, which occured 17 days post-infusion & was unlikely related to treatment. T cell counts increased in a dose dependent manner & increases in neutrophil, platelet, hemoglobin & NK counts were also observed. A ≥ 50% reduction in lymph node area was observed in 12 of 17 evaluable pts (71%), and ≥ 50% decrease in splenic enlargement was observed in 11 of 13 pts with enlarged spleens (85%). Treatment effects were sustained over the 12 week f/u period & observed at all dose levels of XTC administered. Decreases in leukemic cell counts were not observed. 6 pts received a 2nd infusion of XTC (median dose: 77.1 x 10; range: 68.7-96.4 x 10) a median of 10.3 mos (range: 5.8-11.0) following the 1st infusion. The 2nd infusions were well-tolerated, with no SAEs reported. 4 of 5 pts with measurable lymphadenopathy had reductions [median: -38%, range: -67% to +10%], & 2 of 3 pts with splenomegaly had reductions [median: -25%, range: -100% to +33%].,XTC were reproducibly manufactured & were well tolerated. Treatment led to increases in T cell & other blood counts, and significant decreases in lymphadenopathy & splenomegaly. Repeat treatment was well-tolerated, & led to subsequent decreases in lymphadenopathy & splenomegaly. [Table: see text].