Clinical Trial: Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Study of Cellular Immunotherapy Using Central Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Pe

Brief Summary: This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating patients with recurrent or high-risk non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect)

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety and describe the full toxicity profile of cellular immunotherapy utilizing ex vivo expanded autologous central memory T cell (Tcm)-enriched T cells that are genetically modified using a self-inactivating (SIN) lentiviral vector to express a costimulatory cluster of differentiation (CD)19-specific chimeric antigen receptors (CAR) as well as a truncated human epidermal growth factor receptor (EGFR) (CD19R:CD28 zeta/EGFR tau +Tcm) (CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells) in conjunction with a standard myeloablative autologous hematopoietic stem cell transplant (HSCT) for patients with high-risk intermediate grade B-lineage non-Hodgkin lymphoma (e.g., diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL] or transformed non-Hodgkin lymphoma [NHL]).

II. To determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs).

SECONDARY OBJECTIVES:

I. To determine the tempo, magnitude, and duration of engraftment of the transferred T cell product as it relates to the number of cells infused.

II. To study the impact of this therapeutic intervention on the development of normal CD19+ B-cell precursors in the peripheral blood as a surrogate for the in vivo effector function of transferred autologous CD19R:CD28 zeta/EGFR tau +Tcm.

OUTLINE: This is a dose-escalation study of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells. Patients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor per current standard operating policies. Pati
Sponsor: City of Hope Medical Center

Current Primary Outcome:

  • Adverse events attributed to Tcm adoptive transfer as reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 15 years ]
    Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.
  • MTD of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells based on dose limiting toxicities [ Time Frame: Up to day 28 ]
    Graded according to the NCI CTCAE version 4.0.


Original Primary Outcome:

  • Adverse events attributed to Tcm adoptive transfer as reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 15 years ]
    Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.
  • MTD of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells based on dose limiting toxicities [ Time Frame: Up to day 45 ]
    Graded according to the NCI CTCAE version 4.0.


Current Secondary Outcome:

  • Engraftment of the transferred T cell products [ Time Frame: Up to 21 days ]
    Rates and associated 95% confidence limits will be estimated.
  • CD19+ B cell precursors in the peripheral blood as a surrogate for the in vivo effector function of transferred CD19-specific T cells [ Time Frame: Up to 28 days ]
    Rates and associated 95% confidence limits will be estimated.


Original Secondary Outcome:

  • Engraftment of the transferred T cell products [ Time Frame: Up to 21 days ]
    Rates and associated 95% confidence limits will be estimated.
  • CD19+ B cell precursors in the bone marrow as a surrogate for the in vivo effector function of transferred CD19-specific T cells [ Time Frame: Up to 28 days ]
    Rates and associated 95% confidence limits will be estimated.


Information By: City of Hope Medical Center

Dates:
Date Received: March 19, 2013
Date Started: September 2013
Date Completion: September 2018
Last Updated: January 27, 2017
Last Verified: January 2017