Treated T Cells Followed by a Stem Cell Transplant in Treating Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00938626
First received: July 11, 2009
Last updated: September 20, 2013
Last verified: September 2013

July 11, 2009
September 20, 2013
October 2009
October 2011   (final data collection date for primary outcome measure)
  • Cell-based toxicities according to NCI CTCAE v3.0 criteria [ Time Frame: Up to week 4 after chemotherapy ] [ Designated as safety issue: Yes ]
  • Ability to mobilize the number of stem cells required for autologous peripheral blood stem cell transplantation (PBSCT) [ Time Frame: By day 30 after autologous stem cell transplant (ASCT) ] [ Designated as safety issue: Yes ]
  • Cell-based toxicities according to NCI CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
  • Ability to mobilize the number of stem cells required for autologous peripheral blood stem cell transplantation (PBSCT) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00938626 on ClinicalTrials.gov Archive Site
  • Engraftment of neutrophils [ Time Frame: At day 28 after autologous PBSCT ] [ Designated as safety issue: Yes ]
  • Functional changes in immune cell populations [ Time Frame: Prior to immunotherapy (IT), after IT, high dose chemotherapy (HDC)/ autologous stem cell transplant (ASCT) and boost infusion ] [ Designated as safety issue: No ]
  • Assess proportion of erythroid blast-forming unit (BFU)-E, colony forming unit-granulocyte-macrophage (CFU)-GM, CFU-GEMM (granulocyte, erythrocyte, monocyte, megakaryocyte) & erythroid colony forming (CFU-E) [ Time Frame: Prior to induction or salvage chemotherapy; Pre & post IT ] [ Designated as safety issue: No ]
    To determine whether infusions of CD20 Bi-AATC grossly affected the bone marrow progenitor populations.
  • Engraftment of neutrophils at day 28 after autologous PBSCT [ Designated as safety issue: No ]
  • Functional changes in immune cell populations [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Treated T Cells Followed by a Stem Cell Transplant in Treating Patients With Multiple Myeloma
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).

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma and Plasma Cell Neoplasm
  • Biological: anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells
    After completion of induction or salvage chemotherapy, patients receive immunotherapy comprising anti-CD3 x anti-CD20-armed ATC IV weekly for 2 weeks.
  • Procedure: autologous hematopoietic stem cell transplantation
    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.
  • Procedure: peripheral blood stem cell transplantation
    At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation.
Experimental: Armed-activated T cells/Immunotherapy
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.
Interventions:
  • Biological: anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells
  • Procedure: autologous hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
March 2013
October 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00938626
CDR0000646891, P30CA022453, WSU-2008-106
Yes
Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Jeffrey A. Zonder, MD Barbara Ann Karmanos Cancer Institute
Barbara Ann Karmanos Cancer Institute
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP