GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma
We are currently enrolling patients on a phase 1 trial , GINAKIT2, to find the highest and safe dose of GD2-CAR NKT cells (GINAKIT cells) for subsequent study of their anti-tumor activity. This trial wil also provide a preliminary assessment of the effect of these NKT cells on high risk neuroblastoma and the duration of time that the cells last in the body.
This study is for patients diagnosed with relapsed or refractory high-risk neuroblastoma.
This GINAKIT2 phase 1 clinical trial, the first to use of genetically engineered NKT cells in humans, will evaluate the anti-tumor activity of GD2 specific CAR and interleukin-15 expressing autologous NKT cells.
Research in our laboratory has shown that NKTs naturally localize to the tumor site and that their presence in primary tumors correlates with a favorable outcome for children with NB. We have also demonstrated that NKTs destroy tumor-associated macrophages (TAMs), which are cells that support the growth and survival of NBs. We therfore engineered NKT cells to express a chimeric antigen receptor (CAR) on their surface so that they directly kill NB tumor cells.
The CAR is composed of several building blocks that together redirect the NKT cells toward a chosen target. In this case, CARs include a part specific for the GD2 molecule, which is present at high levels in 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 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 > 1 year and < than 21 years old
- Karnofsky/Lansky score ≥ 60%
- Absence of HAMA in patients who have been previously treated with murine antibodies
- Ability to tolerate leukocyte apheresis
- Informed consent and assent, as applicable
- Patients must have an ANC ≥ to 500/µl, and a platelet count > 20,000/µl. Patients may be transfused to obtain the requisite minimum platelet count.
- Pulse oximetry ≥ 90% on room air
- Serum AST ≤ 3 times the upper limit of normal
- Total bilirubin ≤ 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
- Weight ≥ 12 kg
Detailed inclusion and exclusion criteria as listed on clinicaltrials.gov.