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
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Enrollment: 12
Study Start Date: October 2009
Study Completion Date: March 2013
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00938626

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Jeffrey A. Zonder, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Jeffrey Zonder, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00938626     History of Changes
Other Study ID Numbers: CDR0000646891, P30CA022453, WSU-2008-106
Study First Received: July 11, 2009
Last Updated: September 20, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014