GD2 T-Cells + Chemotherapy for Neuroblastoma

(VEGAS Trial)

Not currently recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Disqualifiers: Immune deficiency, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment that combines special immune cells called GD2 T cells (a type of immunotherapy) with a chickenpox vaccine and chemotherapy to combat advanced cancers like neuroblastoma and osteosarcoma. The goal is to determine the safest dose, monitor side effects, and assess whether the treatment can shrink these tumors. Individuals with relapsed or hard-to-treat neuroblastoma or osteosarcoma who have had chickenpox or the vaccine may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that GD2 T cells, studied for treating difficult cancers like neuroblastoma and osteosarcoma, have demonstrated promising safety results. In one study, patients with osteosarcoma who received GD2-CAR T cells did not experience any serious side effects that would limit the dose. Only 15.4% of patients had mild side effects, such as a low-grade fever, indicating the treatment was generally well-tolerated with no severe reactions reported.

Another study involving GD2 T cells in patients with various cancers also found the treatment to be safe. The main focus was to ensure the T cells did not cause harmful reactions. The data so far suggest that GD2 T cells are safe for human use, especially at the doses tested in these studies. While more research continues, the safety results appear positive. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for neuroblastoma involve combinations of chemotherapy, surgery, and radiation. However, GD2 T cells offer a fresh approach by harnessing the body's immune system to fight cancer. Unlike traditional treatments, GD2 T cells are engineered to specifically target and attack neuroblastoma cells. These cells are also derived from the patient's own VZV-specific memory T cells, reducing the risk of unwanted immune reactions. Researchers are excited because this method not only aims to increase treatment precision but also potentially reduces side effects associated with more conventional treatments.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

Research has shown that GD2-targeting CAR T cells could effectively treat high-risk neuroblastoma. One study found that 37% of patients were in complete remission after 6 weeks, 34% after 3 months, and 40% after 6 months. In this trial, participants will receive GD2 T cells combined with a VZV vaccine. These treatments are designed to remain active in the body for extended periods, with some lasting over a year. GD2-CAR T cells use a special gene to help immune cells called T cells locate and destroy cancer cells. This method aims to prolong the treatment effects in the body. Overall, GD2 T cells offer hope for better managing neuroblastoma. ^{2 3 4 6 7}

Who Is on the Research Team?

Cliona Rooney, PhD

Principal Investigator

Baylor College of Medicine

Lisa L Wang, MD

Principal Investigator

Baylor College of Medicine

Sarah Whittle, MD

Principal Investigator

Pediatrics, Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with relapsed or refractory osteosarcoma or high-risk neuroblastoma that hasn't responded to standard treatments. Participants must have a certain level of physical fitness, adequate organ function, and not be pregnant. They should have had prior exposure to the varicella zoster virus (chickenpox) or been vaccinated against it.

Inclusion Criteria

Procurement:

I have recovered from side effects of my previous cancer treatments.

Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria

Known primary immune deficiency or HIV positivity

Pregnant or lactating

You have had allergic reactions in the past to products that contain mouse proteins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-infusion Lymphodepletion

Patients receive 3 daily doses of cyclophosphamide and fludarabine to induce lymphopenia before T cell infusion

3 days

T-cell Infusion

Patients receive GD2-T cells by intravenous line, followed by monitoring for 1 to 4 hours

1 day

1 visit (in-person)

VZV Vaccination

Two weeks after T-cell infusion, patients receive a dose of the VZV vaccine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and tumor measurements

15 years

What Are the Treatments Tested in This Trial?

Interventions

• GD2 T cells

Trial Overview The study tests a combination therapy using GD2-T cells genetically modified to target cancer cells, alongside lymohodepleting chemotherapy and a varicella zoster vaccine. The goal is to determine the highest safe dose of these T cells and assess their effectiveness in treating advanced sarcomas and neuroblastoma.

How Is the Trial Designed?

Group I: GD2 T cells plus VZV vaccine Experimental Treatment 4 Interventions

In this study we will be administering from 1 x 10\^6 to 1 x 10\^9 transduced autologous VZV-specific CTLs, derived from VZV-specific memory T cells, so there will be no risk of alloreactivity. 6.1.1 Pre-infusion lymphodepletion for dose levels 9-11: Patients will receive 3 daily doses of cyclophosphamide together with fludarabine to induce lymphopenia, finishing at least 24 hours before T cell infusion. Cyclophosphamide will be given at a dose of 500 mg/m2/day followed by Fludarabine 30 mg/m2/day.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 phase II study involving 102 patients with high-risk neuroblastoma, the GD2/GD3 vaccine combined with oral β-glucan demonstrated a favorable safety profile, with only mild, self-limited side effects and no severe toxicities.

Higher levels of anti-GD2-IgG1 antibodies (≥ 150 ng/mL) by week 8 were linked to better progression-free survival (32% at 5 years) and overall survival (71% at 5 years), indicating that antibody response may be a key factor in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Impact of Anti-GD2 Antibody Response in a Phase II Ganglioside Vaccine Trial Among Patients With High-Risk Neuroblastoma With Prior Disease Progression. Cheung, IY., Cheung, NV., Modak, S., et al.[2022]

Despite the integration of anti-GD2 monoclonal antibody therapy, the 5-year overall survival rate for high-risk neuroblastoma patients remains around 50%, highlighting the need for improved treatment options.

CAR T cell therapy has shown promise in early clinical trials for neuroblastoma, demonstrating safety and feasibility, but challenges such as T cell persistence and an immunosuppressive tumor environment need to be addressed to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy for Neuroblastoma. Richards, RM., Sotillo, E., Majzner, RG.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40841488/

GD2-targeting CAR T cells in high-risk neuroblastoma The 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 ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210859

GD2-CART01 for Relapsed or Refractory High-Risk ... The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000382

GD2 targeting CAR T cells for neuroblastoma To date the strongest evidence of clinical response and clinical benefit from GD2-targeting CAR-T cells in neuroblastoma is seen in the clinical trial of a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11042400/

Eighteen-year survival after GD2-directed Chimeric Antigen ... In conclusion, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy including one patient ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06684639

NCT06684639 | A Study on the Efficacy of GD2-CAR T ... An open clinical study on the safety and efficacy of autologous GD2-CAR T cells in the treatment of relapsed refractory neuroblastoma conditions.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11097842/

Safety and biological outcomes following a phase 1 trial of ... Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers.

7. cell.com cell.com/cancer-cell/fulltext/S1535-6108(23)00403-8

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 ...