NCT03294954 · Baylor College of Medicine
GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma
(GINAKIT2)
What this study is about
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.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
- Creatinine \< 1.5 times the 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
- Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to procurement Procurement
Exclusion criteria
- Rapidly progressive disease
- History or hypersensitivity to murine protein-containing products
- Tumor causing airway obstruction
- Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
- Severe previous toxicity from cyclophosphamide or fludarabine based on the enrolling physician's assessment
- HIV infection
- History of hypersensitivity, anaphylaxis, and/or adverse event with Etanercept Treatment Inclusion Criteria:
- 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
- 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 times the 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 and expected to tolerate lymphodepletion).
- Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
- Patients must have autologous transduced NKTs with greater than or equal to 20% expression of GD2-specific CAR.
- Informed consent and assent (as applicable) obtained from parent/guardian and child.
- Weight greater than 12kg
- Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to the start of LD Treatment Exclusion Criteria:
- Rapidly progressive disease
- Currently receiving any investigational drugs
- History or hypersensitivity to murine protein-containing products
- Cardiomegaly or bilateral pulmonary infiltrates on chest radiograph or CT. However, patients with cardiomegaly on imaging may be enrolled if they have an assessment of cardiac function (i.e., ECHO or MUGA) within 3 weeks of starting protocol therapy that is within normal limits. Additionally, patients with bilateral pulmonary infiltrates on imaging may be enrolled if the lesions are not consistent with active neuroblastoma (i.e., negative on functional imaging with PET or MIBG, or by pathologic assessment).
- Tumor potentially causing airway obstruction
- Pregnancy or lactation or not willing to use birth control
- Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
- Severe previous toxicity form cyclophosphamide or fludarabine based on the enrolling physician's assessment
- HIV infection
- History of hypersensitivity, anaphylaxis, and/or adverse event with Etanercept
Where
- Houston, Texas
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 19, 2025 · Source of record for eligibility and locations