Texas Children's Cancer and Hematology Center GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (GINAKIT2)

GD2-CAR expressing NKTs have not been tested in patients so far. The purpose of this study is to find the largest effective and safe dose of GD2-CAR NKT cells (GINAKIT cells), to evaluate their effect on the tumor and how long they can be detected in the patient's blood and what affect they have on the patient's neuroblastoma (NB).

Description

In a previous clinical trial, investigators made artificial genes called a chimeric antigen receptors (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). Investigators put these genes into the patients' own T cells and gave them back to patients that had neuroblastoma.

We will expand NKT cells and add GD2-specific chimeric antigen receptors to the cells. We think these cells might be better able to attack NB since they also work by destroying the macrophages that allows the tumor to grow. The chimeric antigen receptor will also contain a gene segment to make the NKT cells last longer. This gene segment is called CD28. In addition, to further improve the antitumor activity of the GINAKIT cells we added another gene expressing a molecule called Interleukin -15 (IL-15). The combination of these 3 components showed the most antitumor activity by CAR expressing NKT cells and improved these cells' survival in animal models.

Eligibility Criteria

• Ages eligible for study: 1 -21 years old
• Relapsed or refractory high risk neuroblastoma
• Life expectancy of at least 12 weeks
• Karnofsky/Lansky score of 60% or greater
• Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)
• Ability to tolerate leukocyte apheresis
• Patients must have an ANC greater than or equal to 500/µl #, platelet count greater than or equal to 20,000/µl. Patients may be transfused to obtain a platelet count greater than or equal to 20,000/µl.
• Pulse Ox greater than or equal to 90% on room air
• Serum AST less than 3 times the upper limit of normal
• Total Bilirubin less than 1.5 times the upper limit of normal
• Creatinine < 1.5 upper limit of normal
• Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
• Weight greater than 12kg

Detailed inclusion and exclusion criteria as listed on clinicaltrials.gov