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).
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
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).
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.
Inclusion Criteria
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
Type of Study:
Interventional
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:
Yes
Principal Investigator
Jeffrey A. Zonder, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000646891
NCT ID:
NCT00938626
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
Name | Location |
|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
