ClinicalTrials.gov record NCT03721068
Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma
A Phase I Study of Autologous Activated T-Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch Administered To Patients With Relapsed/Refractory Neuroblastoma or Relapsed/Refractory Osteosarcoma
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase 1, dose-escalation study gives patients their own T cells that are engineered to target GD2, produce IL‑15, and include an inducible safety switch (iCaspase9). It enrolls people with relapsed or refractory neuroblastoma or osteosarcoma and focuses on safety, finding a tolerated dose, and measuring how the cells behave after infusion. Before the cell infusion, participants receive short lymphodepleting chemotherapy. Follow-up includes both short-term safety monitoring and long-term tracking of the cells and outcomes.
What it is studying. Whether autologous (patient-derived) GD2-directed CAR T-cells that also express IL‑15 and an iCaspase9 safety switch are safe, what dose is tolerated, how the cells expand and persist in the body, and how tumors respond.
What the researchers hope to learn. Determine safety and tolerability of iC9.GD2.CAR.IL-15 T cells; identify the maximum tolerated dose; measure cell expansion and persistence in the body; assess tumor response rates, overall survival, and progression-free survival.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The body has different ways of fighting infections and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are molecules that fight infections and protect your body from diseases caused by bacteria and toxic substances. Antibodies work by sticking to those bacteria or substances, which stops them from growing and causing bad effects. T cells are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been enough to cure most patients. This multicenter study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells (CAR) cells targeted against the disialoganglioside (GD2) antigen that express Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9), also known as iC9.GD2.CAR.IL-15 T cells.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Cyclophosphamide
- Fludarabine
- Biological
- iC9.GD2.CAR.IL-15 T-cells
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- All clinical and laboratory data required for determining eligibility must be available in the subject's medical/research record which will serve as the source document.
- Because of the nature of iC9.GD2.CAR.IL-15 T cell product preparation, subjects will be assessed for initial study enrollment eligibility (prior to cell procurement) and then will have to meet criteria prior to starting lymphodepletion and prior to T cell infusion.
- Inclusion Criteria for the Study:
- Written HIPAA authorization signed by legal guardian.
- Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for <16 years of age).
- Life expectancy ≥12 weeks.
- Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis
- High-risk neuroblastoma with persistent/refractory or relapsed disease, defined as:
- First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.
- First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy. Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).
- Patients must be diagnosed with high risk neuroblastoma at initial diagnosis or if non-high risk at time of initial diagnosis must have had evidence of metastatic progression when >18 months of age as defined in the protocol or relapsed or refractory osteosarcoma that is not responsive to standard treatment.
- Measurable or evaluable disease per Revised INRC for subjects with neuroblastoma or measurable disease by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 criteria for subjects with osteosarcoma.
- Adequate central nervous system function as defined by:
- No known Central Nervous System ( CNS) disease
- No seizure disorder requiring antiepileptic drug therapy
Exclusion criteria
- for the Study Subjects meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion, and cell infusion).
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Has a known additional malignancy that is active and/or progressive requiring treatment.
- History of hypersensitivity reactions to murine protein-containing products.
- History of hypersensitivity to cyclophosphamide or fludarabine.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
In previous studies, it has been shown that when T cells have part of an antibody attached to them, they are better at recognizing and killing cancer cells. The antibody that will be used in this study is called anti-GD2. This antibody floats around in the blood and can detect and stick to cancer cells called neuroblastoma cells because they have a substance on the outside of the cells called GD2. For this study, the anti-GD2 antibody has been changed so that instead of floating freely in the blood, it is now joined to the T cells. However, it is unknown how long the iC9.GD2.CAR.IL-15 T cells last in the body, so their chances of fighting cancer cells are not well known. To improve the tumor-fighting power of GD2-CAR-T cells, two additional components were added to these cells. The IL-15 gene was added so that the GD2-CAR-T cells can attack tumor cells more effectively. Interleukin-15 (IL-15) is a chemical that cells use to communicate with one another. Other research using IL-15 in combination with CAR-T cells has shown there is an increase in the body's ability to allow the CAR-T cells to survive and grow in the body. The iC9 gene was added as an "off switch" so it can stop the activity of the GD2-CAR-T cells if there are any serious bad side effects. Bad side effects seen previously in patients receiving the GD2 antibody alone include pain. In this study, the "stop switch" can be used to turn off the GD2-CAR-T cells if you experience intense pain that does not respond to normal pain treatments. The study will enroll a minimum of 10 adult subjects and 10 pediatric subjects; all subjects will undergo lymphodepletion chemotherapy prior to the cell infusion as outlined in the protocol.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants will be evaluated for eligibility, have cells collected for manufacturing of their own modified T cells, then receive lymphodepletion chemotherapy (intravenous cyclophosphamide and fludarabine) prior to a single infusion of the investigational iC9.GD2.CAR.IL‑15 T cells at an assigned dose. After infusion, participants will be monitored closely for side effects (including immune-related reactions such as cytokine release syndrome and neurotoxicity) and for at least the first 4 weeks for dose‑limiting toxicities. Follow-up includes blood tests and imaging to measure response and to track the modified cells over time; long-term safety and cell persistence will be followed for many years per the protocol.
How the study is structured. An interventional Phase 1 study with a single treatment group and no masking. Participants undergo cell collection, receive lymphodepletion chemotherapy (cyclophosphamide and fludarabine), then a single infusion of engineered CAR T-cells at one of several dose levels. The study uses a dose‑escalation method to find a maximum tolerated dose while monitoring for short-term toxicities; participants are followed for long-term cell persistence and survival outcomes.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry lists this study under Neuroblastoma; Osteosarcoma. Does it apply to my diagnosis?
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Gaucher disease
Important dates
- Study start
- Feb 19, 2019
- Primary completion
- May 19, 2030 (estimated)
- Study completion
- Jun 19, 2044 (estimated)
- Target enrollment
- 18 participants (estimated)
- Last updated on registry
- Mar 27, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Collaborators
- United States Department of Defense
- Bellicum Pharmaceuticals
- National Cancer Institute (NCI)
Participating sites (2)
- Emory - Winship Cancer InstituteWithdrawn
Atlanta, Georgia, 30322 · United States
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillRecruiting
Chapel Hill, North Carolina, 27599-7295 · United States
- Catherine Cheng · 919-445-4208 · UNCImmunotherapy@med.unc.edu
- Caroline Babinec · 919-962-7426 · UNCImmunotherapy@med.unc.edu
- George Hucks, MD
Terms used on this page · explanations by MedicalUpdates.ai
- chimeric antigen receptor
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- legal guardian
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Karnofsky performance status
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- Life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- relapsed
- A condition that improved with treatment and has since returned or worsened.
- complete response
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
- standard treatment
- Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
- exclusion criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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