Treated T Cells Followed by a Stem Cell Transplant in Treating Patients With Multiple Myeloma

OBJECTIVES:

Primary

- To test the feasibility and safety of infusing anti-CD3 x anti-CD20 bispecific
antibody-armed activated T cells (CD20Bi-AATC) before stem cell mobilization and
collection for autologous peripheral blood stem cell transplantation (PBSCT) in
patients with multiple myeloma.

Secondary

- To explore functional changes in immune cell populations as a consequence of
immunotherapy to test the hypothesis that CD20Bi-AATC can induce anti-clonogenic
myeloma precursor cell (CMPC) effect as measured by cytotoxicity; serum cytokine
levels; and serum antibody titers to myeloma cells pre-immunotherapy, after
immunotherapy, and after high-dose chemotherapy and autologous PBSCT.

- To explore whether the infusion of CD20Bi-AATC reduces the proportion of plasma cells
with the CD20+ CMPC phenotype in patients' bone marrow as assessed by multi-color flow
cytometry before and after immunotherapy.

- To assess the proportion of bone marrow colony-forming assays before induction or
salvage chemotherapy, pre-immunotherapy, and post-immunotherapy to determine whether
the infusion grossly affects the bone marrow progenitor populations.

- To explore whether infusions of CD20Bi-AATC induce a B-cell defect causing an
immunoglobulin deficiency after autologous PBSCT.

- To measure immunoglobulin deficiency after autologous PBSCT (e.g., quantitative IgG,
IgM, and IgA levels and number of circulating T- and B-cell subsets).

OUTLINE: After completion of induction or salvage chemotherapy, patients receive
immunotherapy comprising anti-CD3 x anti-CD20-armed ATC IV weekly for 2 weeks. At least 1-3
weeks after the second infusion, patients receive high-dose chemotherapy and then undergo
autologous peripheral blood stem cell transplantation. Patients then undergo leukapheresis
for G-CSF-mobilized autologous T-cells.

Blood samples are collected periodically to evaluate antibody titers to recall antigens;
serum IgG, IgM, and IgA levels; the proportion of circulating B-cells by phenotyping for
CD19, CD20, CD22, CD23, CD4, CD8, and CD38; the ability of peripheral blood mononuclear
cells to kill multiple myeloma cell lines or the patient's own cryopreserved myeloma cells
via cytotoxicity assays and ELISPOT assays; and human anti-mouse antibody responses to
murine IgG2a (OKT3). Bone marrow biopsies are also collected to analyze the phenotype of
cells (CD20+, CD138-, CD27+, CD22, etc.) via flow cytometry and the proportion of plasma
cells via flow cytometry and hematoxylin-and-eosin staining.

After completion of study treatment, patients are followed up for up to 1 year.