Infusion of Allogeneic CD19-Specific T Cells From Peripheral Blood
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 researchers can successfully and
      safely give HSCT patients an infusion of white blood cells (called T-cells) that have been
      genetically changed. The process of changing the DNA (the genetic material in cells) of these
      T-cells is called "gene transfer." 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 standard allogeneic HSCT. Researchers want to find out the
      highest dose of these special T-cells that can be given safely to leukemia and lymphoma
      patients. Researchers also want to learn how long the changed T-cells stay in your body, and
      if adding them to standard transplant can improve how you respond to treatment.
    

Detailed description: 
      Gene Transfer:

      Gene transfer involves drawing blood from a transplant donor, and then separating out the
      T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA,
      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).

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to 1 of 4
      study arms, based on your age, treatment schedule, and disease status:

        -  Participants in Arm 1 will receive the T-cells by vein about 6-12 weeks after the stem
           cell transplant. (Adults participants only)

        -  Participants in Arm 2 will receive the T-cells by vein if, at any point, the disease
           comes back after stem cell transplant. Your doctor may decide that you need to receive
           chemotherapy before you are given the T-cells, in order to clear out the T-cells that
           are in your body already. This may help the infused T-cells work better. If more
           chemotherapy is needed, you will sign another informed consent document, which will the
           chemotherapy and its risks in detail. (Pediatric and adult participants eligible)

        -  Participants in Arm 3 will receive the T-cells by vein about 6-12 weeks after the stem
           cell transplant. (Pediatric participants [ages 1-17] only)

        -  Participants in Arm 4 will be given the T-cells as a scheduled infusion or if the
           disease comes back. This group is also scheduled to receive a stem cell transplant from
           a mismatched family member donor. (Pediatric and adult participants eligible)

      Once you have been assigned to a study arm, you will be assigned to 1 of 4 dose levels of
      genetically-changed T-cells, based on when you joined this study. The first group of
      participants will receive the lowest dose of T-cells, and each new group will receive a
      higher dose of changed T-cells than the group before it, as long as no intolerable side
      effects were seen.

      Chemotherapy and HSCT:

      After your donor's stem cells have been successfully collected, you will be admitted to the
      hospital to receive chemotherapy and the HSCT. 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 HSCT procedure and possible risks, at
      another time.

      The T-cell Infusion:

      After the HSCT, the study chair will decide when you will be eligible for the T-cell
      infusion. You must be at least 42 days past your transplant without any serious evidence of
      active graft versus host disease (GVHD). GVHD occurs when donor cells attack the cells of the
      person receiving the transplant.

      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.

      The T-cell infusion is given by vein, usually over 15-30 minutes. During the infusion, your
      vital signs will be checked. The infusion may be given on one day, or it may be divided into
      two parts at least 24 hours apart. The first part of the infusion will be a much smaller part
      to ensure that you have no immediate side effects.

      Before the T cell infusion, you will receive drugs to lower your risk of allergic reaction to
      the T cells. Acetaminophen (Tylenol®) will be given by mouth, and diphenhydramine (Benadryl®)
      will be given by vein over a few minutes.

      If your cancer returns after the transplant, you may receive an additional T-cell infusion.
      If you receive an additional T-cell infusion, the screening tests will be repeated. The study
      doctor will discuss the results of the repeated screening tests with you. If the screening
      tests show that you are not eligible to receive the additional T-cell infusion, other
      treatment options will be discussed with you.

      Study Tests:

      Within 3 days after the T-cell infusion, and then about 1 week, 2 weeks, 4 weeks, 8 weeks, 3
      months, 6 months and 12 months after the T-cell infusion, the following tests will be
      performed:

        -  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 each time) 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.

        -  Blood (about 4 tablespoons each time) will be drawn for routine tests and tests of your
           blood chemistry, and blood sugars. During the 4 week, 8 week, 3 month, 6 month, and 12
           month visits, part of this blood sample will be used for tests of certain protein
           levels. During the Month 3 visit, part of this blood sample will be used to check for
           HAMA immune system reactions. If you leave the study before the Month 3 visit, blood
           (about 1 tablespoon) may be collected for HAMA immune system reaction testing, if
           possible.

        -  You will have be checked for possible reactions to your treatment, including GVHD and
           graft failure. Graft failure occurs when donor cells may not be able to grow and
           multiply in your body. If this happens, there will be a high risk of infections and/or
           bleeding. If the number of white blood cells does not get back to high enough levels
           within 3 weeks after the transplant, more blood stem cells from the stem cell donor may
           be given.

        -  You may need a skin biopsy or an endoscopy to check for GVHD and/or graft failure, as
           well. To collect a skin biopsy, the biopsy area is numbed with anesthetic, and a small
           amount of skin is collected using a needle or scalpel. An endoscopy is an exam where you
           will be mildly sedated to allow a thin, flexible, lighted tube, called an endoscope, to
           be inserted inside the esophagus, stomach, and first part of the small intestine. This
           will allow the doctor to look for abnormal areas that might not be so easily seen in
           x-rays.

      Within 3 months after the T-cell infusion, you will have CT scans and/or a bone marrow biopsy
      to check the status of the disease. An extra sample of bone marrow aspirate (about 2
      teaspoons each time) will be drawn for research tests whenever a bone marrow aspirate/biopsy
      is being done if possible. These samples will be used for research tests to study how your
      immune system responds to the infusion of T-cells. To collect a bone marrow aspirate, an area
      of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through
      a large needle.

      Length of Study:

      You may continue taking part in this study for up to 3 months. You will be taken off study if
      the disease gets worse, you have any infections, or intolerable side effects occur.

      Your participation on this study will be over once you have completed the planned study
      visits at 3 months after the T-cell infusion.

      Retreatment:

      If you are taken off study because the disease got worse, you may be able to enroll on study
      again once the highest tolerated dose of T-cells is found. If this happens, you will follow
      the same schedule for dosing and study tests as described above.

      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.

      This is an investigational study. The gene transfer or DLI (infusion with genetically-changed
      T-cells) are not commercially available or FDA approved for use in this type of disease.
      Their use in this study is considered investigational. The donor's leukapheresis procedure to
      collect cells for the manufacture of changed T-cells will be provided at no cost to you while
      you are on study.

      Up to 140 patients (and up to 140 donors) will take part in this study. All will be enrolled
      at MD Anderson.
    

Intervention name(s): HSCT; DLI
Intervention type(s): Procedure; Genetic
Intervention description(s): Hematopoietic stem-cell transplant using cells from a matched family donor (matched related allogeneic HSCT) using a non-T cell depleted graft under standard of care procedures; Allogeneic donor lymphocyte infusion (DLI) starting dose not to exceed 10^6/m^2 intravenously between 6 weeks and 12 weeks following allogeneic HSCT.
Other intervention name(s): bone marrow transplant; Hematopoietic stem-cell transplant; Allogeneic donor lymphocyte infusion; CD19-specific T cell Infusion
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Lymphoma; Allogeneic donor lymphocyte infusion; DLI; Hematopoietic Stem Cell Transplantation; HSCT; Bone marrow transplant; CD19-specific T cells; T cell infusion; B-Lineage lymphoid malignancies; CD19+ lymphoid malignancies; Acute lymphoblastic leukemia; ALL; Biphenotypic leukemia CD19+ in advanced remission; Non-Hodgkin's Lymphoma; NHL; Diffuse large B-cell lymphoma; Small lymphocytic lymphoma; Follicular lymphoma; Mantle cell lymphoma with active disease at time of transplant