CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, ALL & CLL

Patients will give us blood to make CD19 CD28 chimeric receptor-T cells in the laboratory. These cells will be grown and frozen for the patient. To make the T cells investigators take the blood and stimulate it with growth factors to make the T cells grow. To get the CD19 antibody (with CD28) to attach to the surface of the T cell, they insert the antibody gene into the T cell. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps us find the T cells in the blood after they inject them using a special laboratory test. Because the patients will receive cells with a new gene in them they will be followed for a total of 15 years to see if there are any long term side effects of gene transfer. If the patient cannot visit the clinic, they may be contacted by the research coordinator or physician.

When the patients enroll on this study, they will be assigned a dose of CD19 CD28 chimeric receptor-T cells.

For those with intermediate or low grade lymphoma/leukemia: The investigators' studies so far have shown that the infused T cells may need to receive an extra boost in order to expand efficiently in the body. Therefore, 2 weeks after T cell infusion, the patient may receive one injection of a drug called ipilimumab, which they believe will help the T cells grow. This drug is approved by the FDA to treat certain cancers, such as melanoma, but the dose of drug used for this study will be lower than those used in those other treatments to avoid side effects.

Patients will be given an injection of cells into the vein through an IV at the assigned dose. The injection will take about 10 minutes. Patients will be followed in the clinic after the injection for up to 3 hours. If after a 4-6 week evaluation period after the infusion, the patient seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), they may be able to receive up to three additional doses of the T cells if they wish. These additional infusions would be at least 4-6 weeks apart and at the same dose level they received the first time or a lower dose. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

To learn more about the way the CD19 CD28 chimeric receptor-T cells are working and how long they last in the body, extra blood will be drawn.

Inclusion criteria

Patients must meet the following eligibility criteria to be included:

• Recurrent B cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of intermediate B cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation. If a patient is less than 18, the lymphoma/leukemia is highly aggressive (i.e. lymphoblastic, Burkitt, ALL).
• Life expectancy of at least 12 weeks
• Recovered from the toxic effects of all prior chemotherapy before entering this study
• ANC greater than 500, HgB greater than 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 greater than 90% on room air
• Karnofsky/Lansky score of greater than 60%
• Available autologous transduced peripheral blood T-cells with greater than/=15% expression of CD19CAR determined by flow-cytometry
• Patients or legal guardians must 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
• Currently receiving any investigational agents or have not received any tumor vaccines within the previous six weeks