GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma
We are currently enrolling patients for GINAKIT2, Phase I study. The purpose is to find the largest effective and safe dose of GD2-CAR NKT cells (GINAKIT cells) and to evaluate their effect on the tumor, how long they can be detected in the patient's blood and whether the GINAKIT cells make neuroblastoma shrink or disappear.
This study is for patients diagnosed with relapsed or refractory high risk neuroblastoma. The patient's neuroblastoma has either come back after treatment or did not respond to the standard medicines used to treat it. Because there is no standard treatment for the patient's cancer at this time, they are being asked to volunteer in a gene transfer research study using special immune cells.
The GINAKIT2 Phase 1 clinical trial will test a new form of cancer immunotherapy that uses natural killer T (NKT) cells to fight neuroblastoma (NB) in children. This study will be the first in history to use genetically engineered NKT cells in humans. Research in our laboratory has shown that NKTs naturally localize to the tumor site and that their presence in primary tumors correlates with favorable outcomes in NB patients. We have also found that NKTs destroy specific cells known as a tumor-associated macrophages (TAMs), which support growth and survival of NB cells. To enable NKTs to directly kill NB tumor cells, we have engineered them to display a chimeric antigen receptor (CAR) on their surface. The CAR is composed of several building blocks originating from different sources that together help redirect the NKT cell toward a chosen target. In this case, CARs include a domain specific for the GD2 molecule, which is present at high levels in many NB tumors and has already led to promising results in clinical trials of GD2-targeted T cells in NB patients. In order to help NKT cells expressing the GD2-CAR (CAR.GD2 NKTs) last longer in patients, we included a domain that makes a mediator known as interleukin-15. This important molecule promotes NKT cell survival and function within tumor tissues. We hypothesize that CAR.GD2-IL15 NKTs will demonstrate anti-tumor activity in NB patients through a combination of directly killing NB cells and indirectly targeting supportive TAMs. Our study will rigorously evaluate the safety of this approach, its efficacy, and determine how long CAR.GD2-IL15 NKTs can be detected in the human body.
- Relapsed or refractory high risk neuroblastoma
- Life expectancy of at least 12 weeks
- Age greater than 1 year and less than 21 years old
- 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
- Informed consent and assent (as applicable) obtained from parent/guardian and child.
- 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
- Serum creatinine normal for age
- 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.