(INCITE-ON) Phase I Study of i15.NKG2D.Zeta-NK Cell Conditioning in the Tumor Micro-environment in Combination With C7R.GD2.CAR-T for the Treatment of Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma
The purpose of this study is to find the largest safe dose of i15.NKG2D.zeta-NK cells in combination with C7R.GD2.CAR-T cells, and additionally to evaluate how long they can be detected in patients' blood and what affect they have on patients' cancer. Patients eligible for this study have neuroblastoma or osteosarcoma that expresses a substance on the cancer cells called GD2. This cancer has either come back after treatment or did not respond to the standard or other investigational treatments or therapies used to treat it. There is no standard treatment for these types of advanced cancers at this time. This is a gene transfer research study using special immune cells called NK cells and T cells. NK cells and T cells are types of white blood cell that help the body fight infection. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: NK cells and T cells. T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. NK cells, another kind of infection-fighting cell, can recognize a wide range of cells in distress, including tumor cells and cells that help protect tumor cells in the cancer environment. Both NK cells and T cells have been used individually to treat patients with cancers. They have shown promise, but have not been strong enough individually to cure most patients. Investigators have found from previous research that we can put a new gene into T cells that will make them recognize GD2, a substance found on almost all neuroblastoma and osteosarcoma cells. We can also put a new gene into NK cells that help them fight the tumor environment. Investigators know that T cells and NK cells need substances called cytokines to survive but the cells do not get enough cytokines after infusion into the body; therefore, the investigators have added the genes C7R and IL15 into the T and NK cells, respectively, to give each cell a constant supply of cytokine that helps them to survive longer. The C7R.GD2.CAR-T cells and i15.NKG2D.zeta-NK cells are investigational products not approved by the Food and Drug Administration.
• Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Or
• Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Karnofsky/Lansky score of 60% or greater.
• Informed consent and assent (as applicable) obtained from parent/guardian and child.
• Greater than 1 year of age.
• Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Or
• Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Karnofsky/Lansky score of 50% or greater
• Pulse Ox greater than or equal to 90% on room air
• AST less than 5 times upper limit of normal (less than 10 times upper normal if known with metastatic liver disease)
• Total bilirubin less than 3 times the upper limit of normal
• Serum creatinine less than 3 times upper limit of normal
• Available autologous T-cells with greater than or equal to 20% expressing GD2.CAR
• Informed consent and assent (as applicable) obtained from parent/guardian and child.
• Greater than 1 year of age.
⁃ Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study.