Phase I Study Of The Administration Of Peripheral Activated T-Cells and EBV Specific CTLs Expressing CD19 Chimeric Receptors For Advanced B-Cell Non-Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia (ATECRAB)

22899-ATECRAB

Patients on this study have a type of lymph gland cancer called non-Hodgkin Lymphoma or chronic Lymphocytic Leukemia. Their lymphoma or CLL has come back or has not gone away after treatment. Because there is no standard treatment for the cancer at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and CLL. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now attached to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T cells seem to be able to kill tumors, but they don't last very long and so their chances of fighting the cancer are limited. Investigators found that T cells work better if they also attach a protein called CD28 to the T cells. This protein makes the T cells more active and survive longer. Also they found that T cells that are also trained to recognize the virus that causes infectious mononucleosis (called Epstein Barr Virus or EBV) can stay in the blood stream for many years. These CD19-CD28 chimeric receptor T cells and CD19 chimeric-EBV specific T cells are investigational products not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe to administer, to see how long each of the T cell populations (CD19-CD28 and CD19-EBV-specific) last, to assess what the side effects are, and to evaluate whether this therapy might help people with lymphoma or CLL.

2009-07-01

2012-05-01

2027-04-01

Active (not recruiting)

Early phase I

3

INCLUSION CRITERIA: FOR TREATMENT: * Recurrent low or intermediate grade B-cell lymphoma or B-CLL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory intermediate B cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation. * CD19-positive tumor * EBV seropositivity (in patient and donor, as applicable) * Recovered from the acute toxic effects of all prior chemotherapy at least a week before entering this study. * Not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six weeks. * No treatment with rituximab within the previous 8 weeks. * ANC \> 500, Hgb \> 8.0\* * Bilirubin less than 3 times the upper limit of normal\* * AST less than 5 times the upper limit of normal\* * Serum creatinine less than 3 times upper limit of normal\* * Pulse oximetry of \> 90% on room air\* * Adequate pulmonary function with FEV1, FVC and DLCO \>35%\* of expected corrected for hemoglobin * Karnofsky or Lansky score of \> 60%. * Available autologous or syngeneic transduced EBV-specific cytotoxic T lymphocytes and peripheral blood T-cells with 15% or greater expression of CD19CAR determined by flow-cytometry. * Patients or legal guardians must understand and sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form. * Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom. EXCLUSION CRITERIA: * History of hypersensitivity reactions to murine protein-containing products. * Pregnant or lactating. * Tumor in a location where enlargement could cause airway obstruction. * Active infection with HIV, HBV, HCV or CMV.

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2024-02-28