Infusion of Allogeneic Umbilical Cord Blood-Derived Cluster of Differentiation Antigen 19 (CD19)-Specific T Cells
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this clinical research study is to learn if an infusion of white blood cells
      (called T cells) that have been genetically changed is safe to give patients who have
      received an umbilical cord blood transplant (UCBT). Researchers want to learn if these
      genetically changed T-cells are effective in attacking cancer cells in patients with advanced
      B-cell lymphoma or leukemia after they have received an UCBT, how long the changed T-cells
      stay in the body, and if adding them to standard transplant could improve how patients
      respond to treatment.

      Funding Source - FDA OOPD
    

Detailed description: 
      T-cell infusion:

      The gene transfer used in this study involves umbilical cord blood cells taken either from
      your UCB unit(s) or from cells left over after your UCB unit has been processed. Researchers
      perform a gene transfer to change the T-cells' DNA (the genetic material of cells), and then
      inject the changed T-cells into the body of the patient receiving the transplant. This
      process is called a modified donor lymphocyte infusion (DLI) or T-cell infusion.

      Chemotherapy and UCBT:

      After the umbilical cord blood unit has been identified for your transplant and after it has
      arrived at the hospital, you will be admitted to the hospital to receive chemotherapy and the
      UCBT. These procedures are not considered part of this research study. You will discuss these
      procedures with a study doctor and sign an informed consent document with specific details of
      the UCBT procedure and possible risks, at another time.

      You will be given standard drugs to help decrease the risk of side effects. You may ask the
      study staff for information about how the drugs are given and their risks.

      The T-cell Infusions:

      After the UCBT, the study doctor will decide when you will be eligible for the T-cell
      infusions. You must be at least 42 days past your UCBT without any serious evidence of active
      graft versus host disease (GVHD). GVHD occurs when the donor cells attack the cells of the
      person receiving the transplant.

      The T-cell infusion is given by vein, usually over 15-30 minutes over 2 days. A smaller dose
      of T cells will be infused on the first day and if this is tolerated the remaining dose of T
      cells will be infused within 72 hours after the first infusion. During both infusions, your
      vital signs will be checked.

      Study Tests:

      Within 30 days before the T-cell infusion:

        -  Blood (about 2 tablespoons) will be drawn to check how well the donated blood cells and
           tissue are mixing with your blood. Researchers use this test to find out how successful
           the transplant is. This is a standard test for patients who have received a transplant.

        -  Blood (about 2 tablespoons) will be drawn for research tests to measure the number of
           B-cells and other (non-transplanted) T-cells.

      Within 7 days before the T-cell infusion:

        -  You will have a physical exam.

        -  You will be checked for possible reactions to your UCBT, including GVHD and graft
           failure.

        -  Blood (about 4 tablespoons) will be drawn for routine tests, to check your immune
           system, and to check for HAMA immune system reactions.

      Within 24 hours, and then about 3 days, 1 week (+/- 2 days), 2 weeks (+/- 2 days), 4 weeks
      (+/- 7 days), 8 weeks (+/- 7 days), 3 months (+/- 7 days), 6 months (+/- 7 days), and 12
      months (+/- 7 days) after the T-cell infusion:

        -  You will have a physical exam.

        -  You will be checked for possible reactions to your treatment, including GVHD and graft
           failure.

        -  Blood (about 4 tablespoons) will be drawn for routine tests.

      About 1 month (+/- 7 days), 2 months (+/- 7 days), 3 months (+/- 7 days), 6 months (+/- 7
      days), and 12 months (+/- 7 days) after the T-cell infusion, blood (about 2 tablespoons) will
      be drawn to check certain protein levels. This may be checked more often, and the protein may
      be replaced, if your doctor thinks it is needed.

      Once during Weeks 2 and 4, and then once a month for 6 months after the T-cell infusion,
      blood (about 1 teaspoon) will be drawn to check your immune system. This blood draw may be
      done at the same time as the blood draws for routine tests when possible, to avoid extra
      "needle sticks".

      After the 2nd T-cell infusion:

        -  Blood (about 2 tablespoons) will be drawn for research tests to check the level of the
           infused T-cells and to measure the number of B-cells and other (non-transplanted)
           T-cells.

      About 30 days and 3, 6, and 12 months after the T-cell infusion:

        -  You will have a physical exam, and you will be checked for possible reactions to your
           treatment, including GVHD and graft failure.

        -  Blood (about 2 tablespoons) will be drawn for research tests to check the level of the
           infused T-cells and to measure the number of B-cells and other (non-transplanted)
           T-cells. °During the Month 3 visit, part of this blood sample will be used to check for
           HAMA immune system reactions.

        -  Urine will be collected for routine tests.

        -  You will have a bone marrow aspiration and biopsy performed to check the status of the
           disease.

        -  If you have lymphoma, you may have a you will have a positron emission tomography -
           computed tomography (PET-CT) scan and/or a CT scan of your neck, chest, abdomen, and
           pelvis to check the status of the disease, if your doctor thinks it is needed.

      Tests and/or procedures may be repeated more often, if your study doctor thinks it is needed.

      Length of Study:

      You may continue taking part in this study for up to 12 months. You will be taken off study
      if the disease gets worse, you have any infections, intolerable side effects occur, you are
      not able to follow study directions, the T-cells do not engraft (grow in your body), or you
      are not able to receive a T-cell infusion.

      You should talk to the study doctor if you want to leave the study early. If you are taken
      off study early, you still may need to return for routine post-transplant follow-up visits,
      or if your transplant doctor decides it is needed.

      Your participation on this study will be over once you have completed the planned study
      visits at 12 months after the last T-cell infusion.

      Long-Term Follow-Up:

      For safety reasons, the U.S. Food and Drug Administration (FDA) requires that patients who
      receive infusions of stem cells treated with a gene transfer procedure must have long-term
      follow-up for at least 15 years after receiving the gene transfer. You will be asked to sign
      a separate consent form for a long-term follow-up study named Protocol 2006-0676.

      This is an investigational study. The gene transfer (or T-cell infusion with genetically
      changed T cells) is not commercially available or FDA approved for use in this type of
      disease. Gene transfer in this study is considered investigational.

      Up to 54 patients will take part in this study. All will be enrolled at MD Anderson.
    

Intervention name(s): T-Cell Infusion; Cord Blood Infusion
Intervention type(s): Genetic; Procedure
Intervention description(s): Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation.; Cord blood infusion on Day 0.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Lymphoma; CD19-specific T cells; Umbilical cord blood transplantation; B-Lineage Lymphoid Malignancies; B-cell leukemia; Acute Lymphoblastic Leukemia; ALL; Biphenotypic Leukemia; Non-Hodgkin's Lymphoma; NHL; Small Lymphocytic Lymphoma; SLL; Chronic Lymphocytic Leukemia; CLL; White blood cells; T cells; Melphalan; Alkeran; Thiotepa; Fludarabine; Fludarabine Phosphate; Fludara; ATG; Antithymocyte Globulin; Thymoglobulin; Rituxan; Rituximab; Cyclophosphamide; Cytoxan; Neosar