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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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).

Brief Summary:

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.


Detailed Summary:

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, p
Sponsor: Barbara Ann Karmanos Cancer Institute

Current Primary Outcome:

  • Cell-based toxicities according to NCI CTCAE v3.0 criteria [ Time Frame: Up to week 4 after chemotherapy ]
  • 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) ]


Original Primary Outcome:

  • Cell-based toxicities according to NCI CTCAE v3.0 criteria
  • Ability to mobilize the number of stem cells required for autologous peripheral blood stem cell transplantation (PBSCT)


Current Secondary Outcome:

  • Engraftment of neutrophils [ Time Frame: At day 28 after autologous PBSCT ]
  • 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 ]
  • 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 ]
    To determine whether infusions of CD20 Bi-AATC grossly affected the bone marrow progenitor populations.


Original Secondary Outcome:

  • Engraftment of neutrophils at day 28 after autologous PBSCT
  • Functional changes in immune cell populations


Information By: Barbara Ann Karmanos Cancer Institute

Dates:
Date Received: July 11, 2009
Date Started: October 2009
Date Completion:
Last Updated: September 20, 2013
Last Verified: September 2013