GINAKIT Cells for Neuroblastoma
(GINAKIT2 Trial)
Trial Summary
What is the purpose of this trial?
This research study combines two different ways of fighting cancer: antibodies and Natural Killer T cells (NKT). Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special white blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. 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. NKT cells are another special subgroup of white blood cells that can specifically go into tumor tissue of neuroblastoma. Inside the tumor, there are other white blood cells called macrophages which help the cancer cells to grow and recover from injury. NKT cells can specifically kill these macrophages and slow the tumor growth. 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. We also found that a medicine called ETANercept can slow down neuroblastoma growth, which might enhance the effects of the modified cells. In this part of our study, we aim to treat children with hard-to-treat neuroblastoma using these modified NKT cells along with ETANercept. Though ETANercept has been used to treat other diseases, such as rheumatoid arthritis in children, there is limited information about the safety, efficacy, and risk of ETANercept treatment in combination with cellular therapies. 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.
Will I have to stop taking my current medications?
The trial requires that you are not currently taking immunosuppressive drugs like corticosteroids, tacrolimus, or cyclosporine, unless the corticosteroid dose is less than 0.5mg/kg/day of prednisone equivalent. If you are on these medications, you may need to stop or adjust them before participating.
What data supports the effectiveness of the GINAKIT Cells treatment for neuroblastoma?
Research shows that combining invariant natural killer T (iNKT) cells with anti-GD2 antibodies can enhance the body's immune response against neuroblastoma, potentially improving treatment outcomes. Additionally, similar therapies using GD2-targeted approaches have shown promise in treating neuroblastoma, suggesting that GINAKIT Cells could be effective.12345
Is GINAKIT Cells treatment safe for humans?
Research shows that GD2-CAR NKT cells, similar to GINAKIT Cells, have been tested in humans with neuroblastoma and are generally safe. In a study, no severe dose-limiting toxicities were observed, and only mild side effects like grade 2 cytokine release syndrome occurred, which were manageable.12467
How is the GINAKIT Cells treatment different from other neuroblastoma treatments?
GINAKIT Cells treatment is unique because it uses genetically engineered natural killer T cells that specifically target the GD2 marker on neuroblastoma cells, enhancing the immune system's ability to attack the cancer without the high toxicity seen in other treatments. This approach combines the benefits of targeted immunotherapy with the natural cancer-fighting abilities of the immune system.13489
Research Team
Andras Heczey, MD
Principal Investigator
Baylor College of Medicine
Eligibility Criteria
This trial is for children and young adults (1-21 years old) with high-risk neuroblastoma that has relapsed or not responded to treatment. They must weigh over 12kg, have a life expectancy of at least 12 weeks, and be able to undergo leukocyte apheresis. Their kidney function, blood counts, liver enzymes, and heart/lung health should meet specific criteria. Those who are pregnant or breastfeeding, have HIV infection or severe disease progression cannot participate.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Lymphodepletion
Participants receive cyclophosphamide and fludarabine intravenously for 2 days and fludarabine alone for one more day before GINAKIT cell infusion.
Treatment
Participants receive GINAKIT cells infusion and ETANercept subcutaneously once per week for 5 doses.
Initial Follow-up
Participants are monitored for side effects and tumor response with follow-up visits at weeks 1, 2, 3, 4, and 8.
Long-term Follow-up
Participants are monitored for long-term safety and effectiveness with visits every 3 months for the first year, every 6 months for the next 4 years, and then annually for the next 10 years.
Treatment Details
Interventions
- GINAKIT Cells
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor College of Medicine
Lead Sponsor
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator