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.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma

• Candidate for high-dose chemotherapy and autologous stem cell transplantation
• No definite morphologic evidence of myelodysplasia on pretreatment bone marrow

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 or Karnofsky PS 70-100%
• ANC > 500/mm^3
• Platelet count ≥ 75,000/mm^3
• Total bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 3 times upper limit of normal
• Creatinine ≤ 2.0 mg/dL
• LVEF ≥ 45%
• Corrected pulmonary diffusion capacity ≥ 50%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infections or other severe medical problems such as adrenal dysfunction
• No other active malignancy (except for nonmelanoma skin cancer) that requires myelosuppressive chemotherapy or radiotherapy
• No HIV infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• On-chemotherapy induction with thalidomide or lenalidomide with dexamethasone is allowed
• No prior stem cell transplantation
• No more than 2 prior treatment regimens (including the one during which patients undergo leukapheresis for T-cells)
• No more than 4 courses of lenalidomide in combination with other agents or as a single agent over a 1-year period
• No other concurrent immunotherapy, radiotherapy, chemotherapy, or anti-myeloma therapy at the time of the anti-CD3 x anti-CD20-armed ATC infusion