Induction of Anti-Myeloma Stem Cell Immunity With Infusions of Autologous Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) (Phase I).
- 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.
- 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Cell-based toxicities according to NCI CTCAE v3.0 criteria
Up to week 4 after chemotherapy
Jeffrey A. Zonder, MD
Barbara Ann Karmanos Cancer Institute
United States: Federal Government
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|