Using Gene Modified Neuroblastoma Cells for the Treatment of Relapsed/Refractory Neuroblastoma

Neuroblastoma cells taken from the patient will be separated in the laboratory and two specially produced human viruses (adenovirus) that carry the lymphotactin and the IL-2 gene were put into the cells. These lymphotactin and IL-2 genes are meant to help the immune system fight the cancer.

The modified cancer cells will be injected under the patient's skin. There will be four shots. The second and subsequent shots will have ten times as many cells producing lymphotactin as the first. We do not know the best amount of special cells to use, so different patients will get different numbers of cells.

Before the second shot, and then again about 2 weeks later, we will remove some of the modified cells from the patient's body and study them. We will do this by removing a section of skin (referred to as a skin biopsy) at the place where the cells were injected. This test will help us to see whether or not the modified cells are killing cancer cells.

To study how the immunity is working in the patient's system, we will take blood samples prior to each injection, two to four days after each injection, and may repeat this 5-7 days after each injection if your doctor thinks that is necessary.

After patients have received the first set of 4 injections a complete evaluation is performed to see how this research treatment is working. If these evaluations look okay and if more injections are available, patients will have the option to receive a second set of 4 injections. If patients receive the second set of 4 injections, they will again have blood samples taken after each injection.

After injections stop, all patients will have blood samples collected once a month for a year, and then once a year for fifteen years.

To see if this research treatment is working, we will do CAT scans, MRIs, or bone scans (these are different types of x-rays). We will also take a bone marrow biopsy (bone marrow will be removed by use of a needle so that it can be looked at under the microscope). These tests will be done prior to treatment and again eight weeks later. In addition, if patients receive the second set of four injections, these tests will be repeated at six months.

• All patients under 21 years of age at diagnosis with recurrent, advanced stage neuroblastoma.
• Patients must have a life expectancy of at least 8 weeks.
• Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute lymphocyte and neutrophil count of >500/mm3 each.
• Patients must not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six weeks.
• Patients must not be HIV-positive.
• Patients must have bilirubin <1.5 mg%.
• Patients must have creatinine <1.5 mg/dl.
• Patients must have ECOG performance status of 0-2.
• Patients must have autologous transduced neuroblastoma cells available that are demonstrably producing >150 pg IL-2/106 cells/24 hr and are secreting Lptn.
• 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.