• • To determine the safety of up to six subcutaneous (SC) injections of autologous tumor cells admixed with autologous gene-modified skin fibroblasts. These fibroblasts are modified ex vivo to express the human CD40 Ligand (hCD40L) and interleukin-2 (hIL [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  

Biological: Tumor Vaccine: CD40 LIGAND AND IL-2 GENE MODIFIED AUTOLOGOUS SKIN FIBROBLASTS AND TUMOR CELLS

CD40L AND IL-2 GENE MODIFIED AUTOLOGOUS SKIN FIBROBLASTS AND TUMOR CELLS dosed at 3 different levels starting at:

Leukemic Blasts 2x10^7 IL-2 Fibroblasts 2x10^7 CD40L Fibroblasts 2x10^5 TOTAL CELLS 4.02x10^7 Each patient will receive 3 injections of their gene modified leukemia cells, each injection separated by 1-2 wks. If there is evidence of response without excessive toxicity and if more transduced cells are available, the pt may receive up to 3 additional SC injections (injections 4-6) separated by 2 weeks.

Before starting in the treatment part of this study, leukemia cells and skin fibroblasts will be collected from the patient - called "procurement" - to allow us to make the vaccine. These leukemia cells are taken from either peripheral blood, leukopheresis product or bone marrow. The fibroblasts will be prepared in the laboratory with specially produced human viruses (adenoviruses) that carry the IL-2 or the CD40L gene. The viruses will "drop off" the genes inside the fibroblasts. The CD40L and IL-2 genes are meant to help stimulate the immune system to fight the leukemia. The modified fibroblasts will be injected with a number of leukemic cells under the skin. All the cells will be irradiated before injection to stop them growing. Patients will receive three shots. Depending on the response, patients may be able to have three additional shots.

In order to collect the skin fibroblasts at the very beginning of the study, and then during the study, we will perform small skin biopsies. In particular before the second shot, and then again about 1 week later, we will look for both the modified and leukemia cells that have been re-injected under the skin. We will do this by taking a skin biopsy from the place where the cells were injected. The area where the skin biopsy will be obtained will be sterilized and then numbed with a local acting agent. The skin will be removed with a "tissue punch" which will cut a circle of approximately 1/4th of an inch into the skin. The site where the skin was removed will be closed with suture, tape or stitches. The area will be covered with dry gauze and adhesive tape. These tests are to see whether the shots are killing leukemia cells and to make sure leukemia cells are not growing at the injection site.

To study how the immunity is working in the system, we will take blood samples before first injection, then weekly for 10 weeks, on week 12, once a month for a year, and then eventually once a year for fifteen years. These samples will be approximately 1 tablespoons of blood, which is considered a safe amount. If the patient has additional injections, blood will be drawn prior to each injection. Additional office visits may be necessary.

Also, patients will need to have a bone marrow test before enrolling on the study and at week 12. If the patient is not responding, they may have treatment with other chemotherapy or radiation. Patients will need to come to the clinic on the days of blood drawing and to be seen at Texas Children's Cancer Center/The Methodist Hospital at weekly intervals for 10 weeks, then every other week for 6 weeks, and then monthly for a year. Thereafter, patients will either be seen in the clinic or contacted by one of the research staff working on this study once a year for 15 years. Additional visits may be necessary.