Treated T Cells Followed by a Stem Cell Transplant in Treating Patients With Multiple Myeloma
Treated T Cells Followed by a Stem Cell Transplant in Treating Patients With Multiple Myeloma
RATIONALE: Giving chemotherapy followed by treated T cells before a stem cell transplant
 stops the growth of cancer cells by stopping them from dividing or by killing them. After
 treatment, stem cells are collected from the patient's blood and stored. High-dose
 chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells
 are then returned to the patient to replace the blood-forming cells that were destroyed by
 the chemotherapy.

 PURPOSE: This phase I trial is studying the side effects and best way to give treated T cells
 followed by 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