3RD GENERATION GD2 SPECIFIC CHIMERIC ANTIGEN RECEPTOR TRANSDUCED AUTOLOGOUS NATURAL KILLER T-CELLS FOR NEUROBLASTOMA

To prepare the neuroblastoma specific Natural Killer T cells (also called GINAKIT cells), about 80 mL (up to 6 tablespoons) of blood will be collected from the patient. For children, the total amount of blood drawn will not be more than 3 ml (less than 1 teaspoon) per 2.2 lbs of body weight. In case the neuroblastoma specific Natural Killer T cells cannot be expanded from the amount of blood that can safely be drawn from the patient, the investigators may attempt to collect white blood cells from the patient by using a special type of blood donation called leukocyte apheresis. Unlike a regular blood draw or "whole blood" donation in which whole blood is removed from patient's body, the apheresis process connects the patient to a machine that removes a particular component of their blood and then returns the rest of the blood back to them. The white blood cells collected during leukocyte apheresis will be used to make the GINAKIT cells. Once collected, the white blood cells will be mixed with a special protein to separate the Natural Killer T cells from the white blood cells using a special machine called a CliniMACS Reagent System in the laboratory. This is an investigational device that is not approved by the FDA. Although this device is not approved for use in this country, it has been in use for years and is approved in other countries. The investigators will put the new genes into patient's Natural Killer T cells by mixing them with a retroviral vector (a special virus that can carry a new gene into cells) containing the new gene called iC9-GD2-CD28-OX40. After the new gene has been put into the Natural Killer T cells, the cells will be tested to make sure that they kill GD2-positive neuroblastoma cells and that the cells are killed by the activation of iC9. The GINAKIT cells may be given back to the patient fresh or frozen. This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 4 different levels) of GINAKIT cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 4 dose levels are studied. If the side effects are too severe, the dose will be lowered or the infusions will be stopped. Before getting the GINAKIT cells, patients will receive cyclophosphamide and fludarabine intraveneously for 2 days and then fludarabine alone for one more day. Patients will then have one day of rest with no chemotherapy before receiving the GINAKIT cells. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital. Patients will need to stay in Houston for 4 weeks after the infusion so the investigators can monitor them for side effects. They will have follow-up visits (at weeks 1, 2, 4, 6, and 8; months 3, 6, 9, and 12; twice a year for 4 years and then once a year for the next 10 years - for a total of 15 years) and scheduled disease evaluations after the GINAKIT cell infusion (at week 4 and then as clinically needed). Also, to learn more about the way the GINAKIT cells are working and how long they last in the body, blood will be obtained before the chemotherapy, on the day of the GINAKIT cell infusion (before and at the end of the infusion) and at the follow-up visits (time points listed above). If the patient experiences no significant side effects during or after the first GINAKIT cell infusion and their cancer remains stable or responds, they may be offered additional doses of the same cell dose in the future.