94 Participants Needed

GD2-targeted CAR T-Cells for Neuroblastoma

Recruiting at 1 trial location
BO
DA
Overseen ByDavid Allen
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment that uses special immune cells, called T cells, to fight cancer. Researchers modify these T cells with a gene to better recognize and attack cancer cells with a marker called GD2. This treatment is known as C7R-GD2.CART cells. The study aims to determine the safest dose of these modified T cells and their effectiveness in shrinking tumors. Suitable candidates for this trial include individuals with neuroblastoma or certain other cancers, such as breast cancer or melanoma, whose cancer has either returned or not responded to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot be on immunosuppressive drugs or investigational drugs. Maintenance therapy with certain non-investigational oral cancer drugs is allowed up to 48 hours before the infusion.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that GD2-targeted CAR T cells could effectively treat certain cancers. One study administered these cells to patients and found them generally safe. No serious side effects occurred, and only 15.4% of patients experienced mild side effects, such as a low-grade fever. Another study discovered that these cells remained in the body for over a year in some patients, suggesting long-term cancer-fighting potential.

However, adding a new gene called C7R to the GD2-CAR T cells to extend their lifespan led to different side effects. In one patient group, 88% experienced mild nerve-related symptoms, which could be managed with treatment.

Overall, these studies suggest that while some side effects exist, the treatment is generally well-tolerated. Ongoing research aims to determine the safest dose and understand how long these cells remain active in the body.12345

Why do researchers think this study treatment might be promising?

Most treatments for neuroblastoma, like chemotherapy and radiation, target rapidly dividing cells but can also harm healthy tissues. In contrast, C7R-GD2.CART cells are unique because they are engineered T-cells that specifically target GD2, a molecule found on neuroblastoma cells, providing a more precise attack on cancer. This targeted approach is promising because it can potentially lead to fewer side effects compared to traditional therapies. Additionally, the treatment is administered without lymphodepletion chemotherapy, which might reduce the overall treatment burden for patients. Researchers are excited about these CAR T-cells because they represent a novel way to harness the immune system's power to fight cancer more effectively and with potentially better outcomes.

What evidence suggests that this trial's treatments could be effective for neuroblastoma and other GD2-expressing cancers?

Earlier research showed that specially engineered T cells targeting GD2 held promise for treating neuroblastoma, a type of cancer. Some patients even achieved complete remission, with positive results observed at 6 weeks, 3 months, and 6 months. However, these T cells did not remain in the body long, disappearing after about 2 weeks. In this trial, participants will receive C7R-GD2.CART cells, modified by adding a new gene called C7R. This modification allows the T cells to survive longer by providing a steady supply of substances that support their survival, potentially enhancing their ability to fight cancer. GD2 is a known target in neuroblastoma, making this approach a hopeful option for patients with GD2-positive cancers.34567

Who Is on the Research Team?

BO

Bilal Omer, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for people aged 1-75 with certain types of cancer (like neuroblastoma, sarcoma, uveal melanoma, breast cancer) that have a substance called GD2 on their cells. The cancers should be resistant to standard treatments or have come back after treatment. Participants need to be relatively healthy otherwise, with a life expectancy of at least 12 weeks and stable organ function.

Inclusion Criteria

You are expected to live for at least 12 weeks.
Informed consent and assent (as applicable) obtained from parent/guardian and child
Your liver function tests are within a certain range.
See 18 more

Exclusion Criteria

You have had an allergic reaction to products containing murine protein, unless you have successfully undergone a desensitization process and re-challenge without another allergic reaction.
I have an autoimmune disease and have been on immunosuppressants in the last 6 months.
Currently receiving other investigational drugs
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Lymphodepletion Chemotherapy

Patients may receive cyclophosphamide and fludarabine to prepare the body for T cell infusion

3 days
3 visits (in-person)

T Cell Infusion

Patients receive GD2-C7R T cells infusion, potentially followed by a second infusion one week later

1-2 weeks
2 visits (in-person)

Initial Follow-up

Patients are monitored for safety and effectiveness with follow-up visits at weeks 1, 2, 4, 6, and 8

8 weeks
5 visits (in-person)

Long-term Follow-up

Patients are monitored for long-term side effects and effectiveness of the gene transfer for up to 15 years

15 years
Bi-annual visits for 4 years, then annual visits

What Are the Treatments Tested in This Trial?

Interventions

  • C7R-GD2.CART cells
Trial Overview The trial tests genetically modified T cells designed to last longer and fight cancer more effectively. These T cells are engineered to recognize and attack GD2 positive cancer cells. Before the T cell infusion, patients may receive chemotherapy to help these special immune cells work better.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Arm B: Standard risk group of all other patientsExperimental Treatment1 Intervention
Group II: Arm A: High-risk group of patients with lung metastasesExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials
114
Recruited
2,900+

Cancer Prevention Research Institute of Texas

Collaborator

Trials
55
Recruited
98,900+

The Methodist Hospital Research Institute

Collaborator

Trials
299
Recruited
82,500+

Published Research Related to This Trial

In a phase 1 study involving 12 children with relapsed/refractory neuroblastoma, treatment with GD2-directed CAR-T cells showed some clinical activity, with three patients experiencing regression of their disease despite no objective clinical responses at the 28-day evaluation point.
The study reported that while two patients experienced significant cytokine release syndrome, there was no on-target off-tumor toxicity, indicating that targeting neuroblastoma with CAR-T cells is a safe approach, although further modifications are needed to enhance the effectiveness and longevity of the CAR-T cells.
Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma.Straathof, K., Flutter, B., Wallace, R., et al.[2021]
In a study involving 19 patients with high-risk neuroblastoma, GD2 chimeric antigen receptor (CAR) T cells were able to induce complete remission in 3 out of 11 patients with active disease, demonstrating their efficacy in treating this aggressive cancer.
The persistence of CAR T cells in the patients was linked to better clinical outcomes, with some CAR-ATCs lasting up to 192 weeks, suggesting that longer-lasting CAR T cells may contribute to improved survival rates.
Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma.Louis, CU., Savoldo, B., Dotti, G., et al.[2023]
The newly developed CAR T cells targeting the GD2 molecule showed strong anti-tumor activity against neuroblastoma in both in vitro assays and a xenograft model, indicating their potential effectiveness in treating this type of cancer.
The anti-GD2 CAR T cells not only infiltrated tumors but also induced significant apoptosis in neuroblastoma cells, suggesting a robust mechanism of action that could lead to complete tumor growth inhibition, warranting further clinical testing.
A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing.Prapa, M., Caldrer, S., Spano, C., et al.[2018]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40841488/
GD2-targeting CAR T cells in high-risk neuroblastomaThe complete remission rate at 6 weeks, 3 months and 6 months reached 37%, 34% and 40%, respectively. GD2-CART01 persisted ≥12 months in 64% of ...
Study Details | NCT04099797 | C7R-GD2.CAR T Cells for ...In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, high grade glioma, ...
GD2 targeting CAR T cells for neuroblastomaGD2 is a well-recognised and validated target antigen for neuroblastoma. CAR-T cells targeting GD2 are a tractable novel therapeutic approach for refractory ...
Phase I Trial of GD2.CART Cells Augmented With ...CARTs experienced temporary improvement from baseline neurologic deficits (range, 2 to >12 months), and seven of eight (88%) remained eligible ...
C7R-GD2.CART Cells for Patients With Relapsed or ...We saw that the cells did grow for a while, but started to disappear from the blood after 2 weeks. We think that if T cells are able to last longer they may ...
NKG2D.Zeta-NK Cell Conditioning With C7R.GD2.CAR-T ...The purpose of this study is to find the largest safe dose of i15.NKG2D.zeta-NK cells in combination with C7R.GD2.CAR-T cells ...
GD2-CAR T cells in patients with osteosarcoma and ...The infusions of GD2-CAR T cells were safe; no dose-limiting toxicities were detected and 15.4% (2/13) patients experienced grade 1 cytokine ...
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