CD19-specific T-cell for Chronic Lymphocytic Leukemia (CLL)
Condition: Advanced Cancers; Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this clinical research study is to find the highest tolerable dose of T cells
      that can be given in combination with standard chemotherapy to patients with CLL. The safety
      of this combination will also be studied.

      The T cells being used in this study are a type of white blood cell that will be taken from
      your blood and then genetically changed in a laboratory. The process of changing the DNA (the
      genetic material of cells) of the T cells is called a gene transfer. After the gene transfer
      is complete, the genetically changed T-cells will be put back into your body. These T cells
      may help prevent cancer cells from coming back.
    

Detailed description: 
      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a dose
      level of genetically changed T cells, based on when you joined this study. Up to 4 dose
      levels of T cells will be tested. Up to 3 participants will be enrolled at each dose level.
      The first group of participants will receive the lowest dose level. Each new group will
      receive a higher dose of than the group before it, if no intolerable side effects were seen.
      This will continue until the highest tolerable dose of T cells is found.

      All participants will receive the same dose of chemotherapy.

      T Cell Collection (leukapheresis or standard blood draw):

      Within 30 days after you have completed the screening tests, you will have leukapheresis
      performed at the Apheresis Clinic at MD Anderson.

      Before the leukapheresis:

        -  You will have a physical exam, including measurement of your height, weight, and vital
           signs.

        -  Your medical history will be recorded.

        -  Blood (about 4 tablespoons) will be drawn for routine tests and to measure levels of
           certain proteins.

      A leukapheresis is a procedure used to remove blood from the body so that specific blood
      cells, such as T cells, can be collected. After the specific cells have been collected, the
      remaining blood is returned to the body.

      To perform a leukapheresis, blood will be drawn through a needle in a vein in one arm, then
      passed though a machine to collect white blood cells, and then the remaining blood will be
      returned back to you through a needle in a vein in the other arm. The procedure will take
      about 3 hours to complete.

      If the doctor thinks it is in your best interest, instead of having a leukapheresis, blood
      (about 13.5 tablespoons) will be drawn to collect white blood cells instead.

      If certain types of unwanted T cells are growing too much, an investigational device called a
      CliniMACS® system will be used to filter out the unwanted T cells using a magnet.

      It will take about 7 weeks to modify and grow the necessary number of genetically modified T
      cells in the lab. If researchers are not able to collect enough T cells for your assigned
      dose level, you will be taken off study. Other options will be discussed with you by your
      doctor.

      Chemotherapy:

      Before you receive the T cell infusion, you will receive your standard chemotherapy with
      fludarabine and cyclophosphamide through a catheter (plastic tube) inserted into a large
      chest vein or through an intravenous needle (IV) inserted in a vein in your arm.

      Fludarabine will be given by vein over 30 minutes daily for 3 days.

      Cyclophosphamide will be given by vein over 3 hours daily for 3 days.

      Study Tests Before the T cell Infusion:

      Within 60 days before the T cell infusion:

        -  You will be asked about any side effects that you may have had.

        -  Blood (about 2 tablespoons) will be drawn for tests to look at your DNA to check the
           status of the disease. This may be performed any time before or during the study.

        -  Mouse protein antibodies are used in the gene transfer process. If your body becomes
           immune to these proteins, your body may develop antibodies against the mouse antibodies
           (called "human anti-mouse antibodies" or HAMA). Part of the blood sample will be used to
           compare against another sample of blood collected after the gene transfer is complete to
           check for HAMA.

        -  You will have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan to check
           your heart function.

        -  You will have lung function tests.

        -  If the study doctor thinks it is needed, you will have a bone marrow biopsy/aspiration
           to check the status of the disease. To collect a bone marrow biopsy/aspirate, an area of
           the hip or chest bone is numbed with anesthetic, and a small amount of bone and bone
           marrow is withdrawn through a large needle.

        -  If the study doctor thinks it is needed, you will have computed tomography (CT) scans
           and/or positron emission tomography (PET) scans to check the status of the disease.

      Within 7 days before starting chemotherapy:

        -  You will have a physical exam, including measurement of your weight, and vital signs.

        -  Your medical history will be reviewed and any updates will be recorded.

        -  You will be asked about any side effects that you may have had.

        -  Blood (about 2 tablespoons) will be drawn for routine tests. Part of this blood sample
           will be used for a pregnancy test if you are able to become pregnant. To continue your
           participation in this study, you cannot be pregnant.

      T-cell Infusion (gene transfer):

      The T cell infusion will be given by vein over about 15-30 minutes.

      Before the infusion, you will receive drugs to lower your risk of allergic reaction to the T
      cells. Tylenol® (acetaminophen) will be given by mouth and Benadryl® (diphenhydramine) may be
      given by mouth or by vein over a few minutes.

      Your vital signs will be checked during and after the T cell infusion.

      Study Tests after the T cell infusion:

      Within 3 days, 1 week (+/- 2 days), 2 weeks (+/- 3 days), 1 month (+/- 7 days), 6 months (+/-
      14 days), and 12 months (+/- 14 days) after the T-cell infusion, the following tests and
      procedures will be performed:

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your medical history will be reviewed and any updates will be recorded.

        -  You will be asked about any side effects that may have had.

        -  Blood (about 4 tablespoons) will be drawn for routine tests, tests to measure levels of
           certain proteins, and tests to look at your DNA to check the status of the disease. Part
           of this blood sample will be used to compare against a sample of blood that was
           collected before the gene transfer to check for HAMA (at 6 months after the T cell
           infusion only). At 1, 6, and 12 months after the T-cell infusions, part of this blood
           sample will be used to measure levels of certain proteins.

        -  Blood (about 4 tablespoons) will be drawn to learn how your body's immune system
           responds to the T-cell infusion.

      At around 6 and 12 months after the T-cell infusion, if the study doctor thinks it is needed
      you will have CT scans, PET-CT scans, and/or a bone marrow biopsy to check the status of the
      disease.

      Length of Study:

      Your participation on this study will be over after you have completed the last planned study
      visit at about 12 months after the T cell infusion is complete. You may be taken off study
      early if the disease gets worse, you experience any intolerable side effects, you cannot keep
      your appointments, if your doctor thinks it is in your best interest, or if you are unable to
      receive the T-cell infusion.

      If you leave the study early for any reason and you received T-cells, if possible, blood
      (about 2 teaspoons) will be collected. This blood sample will be used to compare against
      another sample of blood collected after the gene transfer is complete to check for HAMA.

      Long-Term Follow-Up Study:

      For safety reasons, the U.S. Food and Drug Administration (FDA) requires that patients who
      receive stem cells infusions that have been 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 Protocol 2006-0676.

      This is an investigational study. Fludarabine and cyclophosphamide are commercially available
      and FDA approved for the treatment of CLL. The T cell infusion using a gene transfer
      procedure is not commercially available or FDA approved. At this time, T cell infusions using
      a gene transfer procedure is only being used in research.

      Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.
    

Intervention name(s): Leukapheresis; Fludarabine; Cyclophosphamide; T-cell Infusion
Intervention type(s): Procedure; Drug; Drug; Procedure
Intervention description(s): Blood drawn through a needle in a vein in one arm, then passed though a machine to collect white blood cells, and then remaining blood returned back to patient through a needle in a vein in other arm. Procedure will take about 3 hours to complete.; 25 mg/m2 by vein on Days -5 to Day -3.; 250 mg/kg by vein on Days -5 to -3.; Beginning dose of genetically modified cells is > 5x10^7/m2 but less than or equal to 5 x10^8/m2 infused on Day 0.
Other intervention name(s): Fludarabine Phosphate; Fludara; Cytoxan; Neosar
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Advanced Cancers; Leukemia; B-cell Chronic Lymphocytic Leukemia; B-CLL; CD19 positivity; CD19-specific T cells; T-Cell Infusion; Gene Transfer; Leukapheresis; Fludarabine; Fludarabine Phosphate; Fludara; Cyclophosphamide; Cytoxan; Neosar