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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).

Phase 1
18 Years
Open (Enrolling)
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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.

Inclusion Criteria


- Diagnosis of multiple myeloma

- Candidate for high-dose chemotherapy and autologous stem cell transplantation

- No definite morphologic evidence of myelodysplasia on pretreatment bone marrow


- 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

- No other active malignancy (except for nonmelanoma skin cancer) that requires
myelosuppressive chemotherapy or radiotherapy

- No HIV infection


- See Disease Characteristics

- On-chemotherapy induction with thalidomide or lenalidomide with dexamethasone is

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Cell-based toxicities according to NCI CTCAE v3.0 criteria

Outcome Time Frame:

Up to week 4 after chemotherapy

Safety Issue:


Principal Investigator

Jeffrey A. Zonder, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Federal Government

Study ID:




Start Date:

October 2009

Completion Date:

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • refractory multiple myeloma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201