Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma
Condition: B Cell Leukemia; B Cell Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a study for children who have been previously treated for Leukemia/Lymphoma. In
      particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B
      cells (a type of white cell), which contain the cancer. This is a new approach for treatment
      of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's
      white blood cells (T cells) and modify them in order to target the cancer.

      The subject's T cells will be modified in one or two different ways that will allow the cells
      to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells the T
      cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells
      (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in
      order to allow the modified T cells to recognize your tumor cells but not other normal cells
      in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19)
      T-cells.
    

Detailed description: 
      At entry subjects will be staged and the suitability of their T cells for CART-19
      manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed to
      obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19 manufacturing.
      The T cells will be purified from the PBMC, transduced with CART-19 lentiviral vector,
      expanded in vitro and then frozen for future administration. Chemotherapy will then be given.
      Following tumor burden reassessment, CART-19 cells will be thawed and infused.

      Subjects will have blood tests to assess safety, and engraftment and persistence of the
      CART-19 cells at regular intervals through four weeks after their last infusion of the study.
      Following the 6 months of intensive follow-up, subjects will be evaluated quarterly for two
      years with a medical history, a physical examination, and blood tests. Following this
      evaluation, subjects will enter a roll-over study for annual follow-up by phone and
      questionnaire for an additional thirteen years to assess for the diagnosis of long-term
      health problems, such as development of new malignancy.

      Primary objectives:

        1. Determine the safety and feasibility of administration of chimeric antigen receptor T
           cells transduced with the anti-CD 19 lentiviral vector (referred to as "CART-19" cells).

        2. Determine duration of in vivio survival of CART-19 cells. Real Time polymerase chain
           receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival
           of CART-19 TCR:4-1BB and TCR cells over time.

      Secondary objectives:

        1. For patients with detectable disease, measure anti-tumor response due to CART-19 cell
           infusions.

        2. To determine if the 4-1BB transgene is superior to the TCR only transgene as measured by
           the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.

        3. For patients with stored or accessible tumor cells (such as patients with active chronic
           lymphocytic leukemia (CLL), acute lymphoblastic leukema (ALL), etc) determine tumor cell
           killing by CART-19 cells in vitro.

        4. Determine if cellular or humoral host immunity develops against the murine anti-CD19,
           and assess correlation with loss of detectable CART-19 (loss of engraftment).

        5. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)
    

Intervention name(s): CART-19
Intervention type(s): Biological
Intervention description(s): Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Biological: CART19