Subjects that have relapsed or refractory neuroblastoma are invited to take part in this gene transfer research study.
We have found from previous research that we can put a new gene called a chimeric antigen receptor (CAR) into T cells that will make them recognize neuroblastoma cells and kill them. In a previous clinical trial, we used a CAR that recognizes GD2, a protein found on almost all neuroblastoma cells (GD2-CAR). We put this gene into T cells and gave them back to patients that had neuroblastoma. The infusions were safe and in patients with disease at the time of their infusion, the time to progression was longer if we could find GD2 T cells in their blood for more than 6 weeks. Because of this, we think that if T cells are able to last longer, they may have a better chance of killing neuroblastoma tumor cells.
Therefore, in this study we will add new genes to the GD2 T cells that can cause the cells to live longer. These new genes are called CD28 and OX40. The purpose of this study will be to determine the highest dose of iC9-GD2-CD28-OX40 (iC9-GD2) T cells that can safely be given to patients with relapsed/refractory neuroblastoma.
In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and we think that it will allow the T cells we infuse to expand and stay longer in the body, and potentially kill cancer cells more effectively.
The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine.
Additionally, to effectively kill the tumor cells, it is important that the T cells are able to survive and expand in the tumor. Recent studies have shown that solid tumors release a substance (PD1) that can inhibit T cells after they arrive into the tumor tissue. In an attempt to overcome the effect of PD1 in neuroblastoma we will also give a medication called pembrolizumab.
Who can participate
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
PROCUREMENT
* High risk neuroblastoma with persistent or relapsed disease
* Life expectancy of at least 12 weeks
* Karnofsky/Lansky score of 60% or greater
* Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)
* Informed consent and assent (as applicable) obtained from parent/guardian and child
TREATMENT:
* High risk neuroblastoma with persistent or relapsed disease
* Life expectancy of at least 12 weeks
* Karnofsky/Lansky score of 60% or greater
* Patients must have an ANC greater than or equal to 500, platelet count greater than or equal to 20,000
* Pulse Ox greater than or equal to 90% on room air
* AST and ALT less than 5 times the upper limit of normal
* Total bilirubin less than 3 times the upper limit of normal
* Serum creatinine less than 3 times upper limit of normal. Creatinine clearance is needed for patients with creatinine greater than 1.5 times upper limit of normal
* TSH normal for age. Patients using thyroid medication to facilitate a euthyroid state must be on a stable dose for at least 1 month prior to planned infusion
* Recovered from acute effects of all prior chemotherapy. If some effects of therapy have become chronic (i.e., treatment associated thrombocytopenia), the patient must be clinically stable and meet all other eligibility criteria
* Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodi…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Dose limiting toxicities at 6 weeks post T cell infusion
Timeframe: 6 weeks after infusion of the last dose of iC9-GD2 T cells to all patients on the study