Houston, Texas 77030


Purpose:

Sometimes researchers change the DNA (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, 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. The goal of this clinical research study is to find the highest tolerable dose of genetically changed T-cells that can be given to patients. Researchers want to learn if these genetically changed T-cells may be able to attack cancer cells in patients with advanced B-cell lymphoma or leukemia.


Study summary:

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 begin to receive the cell product. 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. It will take about 7 weeks to modify and grow the necessary number of genetically changed T-cells in the lab. T Cell Collection for Treatment Arm 1: Within 30 days before the T-cell collection: - You will have a physical exam. - You will have a chest x-ray. - You will have an electrocardiogram (EKG) to check your heart function. - Blood (about 4 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 take part in this study, you must not be pregnant. - HIV blood test. State law requires that the results of positive tests for HIV be reported to a local health agency. - 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 with another sample of blood collected after the gene transfer is complete to check for HAMA. Within 30 days after you have completed the screening tests, you may have leukapheresis performed at the Apheresis Clinic at MD Anderson. Before the leukapheresis: - You will have a physical exam. - Blood (about 4 tablespoons) will be drawn for routine tests and to measure levels of certain proteins. If you have leukapheresis performed to collect T-cells, the study doctor will discuss this procedure with you in more detail and you will be asked to sign a separate consent. If the doctor thinks it is in your best interest, instead of having leukapheresis, blood (about 13½ tablespoons) will be drawn to collect white blood cells. If not enough T cells can be collected, the leukapheresis or blood draw to collect white blood cells may be repeated. Chemotherapy: Before you receive the T cell infusion, you may receive standard chemotherapy (cyclophosphamide with or without fludarabine) by vein. The goal of this chemotherapy is to help the infused T-cells work better. If the doctor does not think it is in your best interest, you may not receive any chemotherapy. Your doctor will make this decision, and you will sign a separate consent for chemotherapy that will explain the drugs and their risks. Study Visits Before T-cell Infusion: Within 60 days before the T-cell infusions: - Blood (about 2 tablespoons) will be drawn to check the status of the disease. - 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 a lumbar puncture to check the status of the disease. To perform at lumbar puncture (also called a spinal tap), a special needle is inserted into the lower back through the space between the bones. The needle is used to withdraw a sample of the fluid that surrounds the spinal cord. - 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 (if you receive it): - You will have a physical exam. - 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. - Blood (about 4 tablespoons) will be drawn to learn how your body's immune system responds to the T-cell infusion. T-cell Infusion: The T-cell infusion will be given by vein over about 15-30 minutes either all on one day or split into two days. It can be given up to 1 month after your last chemotherapy treatment. 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. Study Tests After T cell infusions: Within 3 days, 1 week (+/- 2 days), 2 weeks (+/- 3 days), 1 month (+/- 7 days), 3 months (+/- 7 days), 6 months (+/- 14 days), and 12 months (+/- 14 days) after the T-cell infusions, the following tests and procedures will be performed: - You will have a physical exam. - Blood (about 4 tablespoons) will be drawn for routine tests, tests to measure levels of certain proteins, and tests 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 (6 months after the T-cell infusion only). If you leave the study early and the study doctor thinks it is possible, blood (about 2 teaspoons) will be drawn for HAMA testing at that time. - Blood (about 4 tablespoons) will be drawn to learn how your body's immune system responds to the T-cell infusion (1, 3, 6, and 12 month timepoints only). - Within 60 days of the T-cell infusion a test will be done to test your lung function (PFT's). At around 1, 3, 6, and 12 months after the last T-cell infusion, if the study doctor thinks it is needed, you will have 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 about 12 months after the last T-cell infusion is complete. You may be taken off study early if the disease gets worse, if you cannot keep your appointments, if your doctor thinks it is in your best interest, if the cells cannot be manufactured or collected, or if you are unable to receive the T-cell infusion(s). 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). In the event of death due to any cause, an autopsy will be requested from your family if it is possible. This is an investigational study. 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 are only being used in research. Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.


Criteria:

Inclusion Criteria: 1. Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, Non-Hodgkin's Lymphoma, Small Lymphocytic Lymphoma, or Chronic Lymphocytic Leukemia with active disease defined by presence of >5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease. Patients must have measurable disease at time of study treatment. 2. Confirmed history of CD19 positivity by flow cytometry for malignant cells. 3. Lansky/Karnofsky Performance Scale > 60%. 4. Patient able to provide written informed consent. Parent or guardian of minor patient able to provide written informed consent. 5. Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676. Parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676. 6. Age 1-80 years of age. Three adult patients will be treated before allowing treatment of children, as defined as younger than 18 years old. Exclusion Criteria: 1. Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females. 2. Patients with known allergy to bovine or murine products. 3. Positive serology for HIV. 4. Active hepatitis B or active hepatitis C. 5. Has received DLI product within 6 weeks of CAR T cell infusion. 6. Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T cell infusion; HSCT >3 months from CAR T cell infusion eligible.


NCT ID:

NCT02529813


Primary Contact:

Principal Investigator
Partow Kebriaei, MD
M.D. Anderson Cancer Center

Partow Kebriaei, MD
Phone: 713-792-8750


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States



There is no listed contact information for this specific location.

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 17, 2017

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