GD2 CAR T Cells for Brain and Spinal Cord Gliomas

Overseen By Courtney Erickson, RN, BSN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Corticosteroids, Alternative therapies

Disqualifiers: Bulky tumor, Swallowing dysfunction, Infections, others

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

Compensation: Varies

Number of Visits: 28

Duration: 4 weeks

97 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called GD2-CAR T cells to determine if they can be made from the immune cells of children and young adults. It focuses on brain and spinal cord tumors known as gliomas, specifically those with the H3K27M mutation. Participants should have this mutation and have completed standard radiation therapy. This study targets individuals previously diagnosed with these specific gliomas who continue to face challenges despite earlier treatments. As a Phase 1 trial, the research seeks to understand 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 taking your current medications, but ongoing use of dietary supplements, alternative therapies, extreme diets, or any medication not approved by the investigators is not allowed. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that GD2 CAR T cells are being tested for safety in treating certain aggressive brain and spinal cord tumors in young patients, specifically diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). Previous studies have found that GD2 CAR T cells can shrink tumors in some cases, suggesting potential effectiveness, but their safety is still under careful observation.

In earlier studies, some patients tolerated GD2 CAR T cell therapy well. However, any new treatment, especially in early trials, can have side effects. Researchers are still studying the specific side effects of GD2 CAR T cells. The treatment involves administering these modified cells in varying amounts to determine what is safe and effective.

As this is an early-stage trial, the primary goal is to identify the safest dose. Participants may experience some side effects as researchers determine the best way to use GD2 CAR T cells. These trials are crucial to ensure the treatment's safety for future use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain and spinal cord gliomas, which often involve surgery, radiation, and chemotherapy, GD2 CAR T cells offer a novel approach by harnessing the power of the immune system. This treatment is unique because it involves genetically modifying a patient's own T cells to specifically target and attack cancer cells that express the GD2 protein. Researchers are excited about GD2 CAR T cells because they provide a more precise attack on cancer cells, potentially leading to fewer side effects than traditional treatments. Additionally, the delivery of these T cells directly into the cerebrospinal fluid allows them to reach the tumor more effectively, improving the chances of a successful outcome.

What evidence suggests that GD2 CAR T cells might be an effective treatment for gliomas?

Research has shown that a new treatment using GD2 CAR T cells, tested in this trial, may help treat certain brain and spinal cord tumors called diffuse midline gliomas (DMG) and diffuse intrinsic pontine gliomas (DIPG). These special cells can attack cancer and have shrunk tumors in children and young adults. Some patients have experienced significant tumor reduction, with effects lasting a long time. Early studies suggest that targeting GD2, a component of the cancer cells, can be effective against these difficult-to-treat tumors. This new approach is under close observation as it might lead to new ways to treat these challenging cancers. ^{1 3 4 5 6}

Who Is on the Research Team?

Michelle Monje

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 2 to 50 with H3K27M-mutant brainstem glioma (DIPG) or spinal cord glioma (DMG), post-radiation therapy, and without recent systemic treatments. US residents who can consent, practice birth control, have a negative pregnancy test if applicable, and have normal organ/marrow function are eligible. Exclusions include uncontrolled infections, certain tumor locations, ongoing corticosteroid use, significant medical conditions that could affect the study's outcome.

Inclusion Criteria

Pregnancy Test: Females of childbearing potential must have a negative serum or urine pregnancy test, Contraception: Subjects of child bearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative lymphodepletion regimen or for as long as GD2-CAR T cells are detectable in peripheral blood or cerebrospinal fluid (CSF)

My cancer is a specific type that affects the brainstem or spinal cord and has a certain genetic mutation.

I can understand and agree to participate, or if under 18, I can verbally agree if over 7 years old.

Exclusion Criteria

I have received GD2-antibody therapy before.

I have HIV or hepatitis B/C, or a history of hepatitis with no detectable viral load.

You have a significant problem swallowing or other issues with the nerves in your brainstem.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GD2-CAR T cells after lymphodepletion chemotherapy with cyclophosphamide and fludarabine, followed by dose escalation of GD2-CAR T cells

4 weeks

Multiple visits for chemotherapy and T cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose limiting toxicities and radiographic response

24 months

Regular visits at Day 28, 3 months, 6 months, 9 months, 12 months, and 24 months post-infusion

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• GD2 CAR T cells

Trial Overview The trial tests GD2-CAR T cells made from patients' immune cells against DIPG/DMG tumors in the brainstem or spinal cord. It checks if these CAR T cells can be created successfully and includes preparatory chemotherapy with Fludarabine and Cyclophosphamide before introducing the GD2-CAR T cells.

How Is the Trial Designed?

Group I: ARM D Experimental Treatment 4 Interventions

GD2CART will be administered in escalating doses on Day 0 in hospitalized subjects with either DIPG, spinal DMG, or high risk features. Intracerebroventricularly after administration of conditioning lymphodepletion chemotherapy regimen with rituximab, cyclophosphamide and fludarabine * Dose Level -1: 10x10\^6 transduced T cells (±20%) * Dose Level 1: 30x10\^6 transduced T cells (±20%) * Dose Level 2: 50x10\^6 transduced T cells (±20%)

Group II: ARM C Experimental Treatment 3 Interventions

GD2CART will be administered in escalating doses on Day 0 in hospitalized subjects with either DIPG or spinal DMG Intracerebroventricularly after administration of conditioning lymphodepletion chemotherapy regimen with cyclophosphamide and fludarabine * Dose Level -1: 10x10\^6 transduced T cells (±20%) * Dose Level 1: 30x10\^6 transduced T cells (±20%) * Dose Level 2: 50x10\^6 transduced T cells (±20%)

Group III: ARM B Experimental Treatment 1 Intervention

GD2CART will be administered on Day 0 in hospitalized subjects with either DIPG or spinal DMG Intracerebroventricularly, without conditioning lymphodepletion chemotherapy * Dose Level -1: 10x10\^6 transduced T cells (±20%) * Dose Level 1: 30x10\^6 transduced T cells (±20%) * Dose Level 2: 50x10\^6 transduced T cells (±20%) * Dose Level 3: 100x10\^6 transduced T cells (±20%)

Group IV: ARM A Experimental Treatment 3 Interventions

GD2CART will be administered on Day 0 in hospitalized subjects with either DIPG or spinal DMG Intravenously, after conditioning lymphodepletion chemotherapy regimen with cyclophosphamide and fludarabine * Dose Level -1: 3x10\^5 transduced T cells/kg(± 20%) * Dose Level 1: 1x10\^6 transduced T cells/kg (± 20%) * Dose Level 2: 3x10\^6 transduced T cells/kg (± 20%)

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Crystal Mackall, MD

Lead Sponsor

Trials

6

Recruited

240+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Alex's Lemonade Stand Foundation (ALSF)

Collaborator

Parker Institute for Cancer Immunotherapy

Collaborator

Trials

12

Recruited

460+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

CureSearch

Collaborator

Trials

3

Recruited

130+

Published Research Related to This Trial

In a first-in-human phase I trial involving four patients with H3K27M-mutated DIPG or spinal cord DMG, GD2-directed CAR T cells showed promising clinical and radiographic improvements in three out of four patients, indicating potential efficacy of this treatment.

The treatment was associated with manageable toxicity primarily related to the tumor's location, and no on-target, off-tumor toxicity was observed, suggesting a favorable safety profile for GD2-CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Majzner, RG., Ramakrishna, S., Yeom, KW., et al.[2023]

Patient-derived glioblastoma cells expressing high levels of GD2 antigen can be effectively targeted by CAR T cell therapy, showing promising antitumor activity in both 2D and 3D models.

Intracerebral delivery of CAR T cells significantly improved survival times in orthotopic NOD/SCID models of glioblastoma, demonstrating a safe and effective route for treatment without side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2 CAR T cells against human glioblastoma. Prapa, M., Chiavelli, C., Golinelli, G., et al.[2021]

Infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells in eight patients with GD2-positive glioblastoma (GBM) was found to be safe and well tolerated, with no severe adverse events reported.

Of the eight patients, four experienced a partial response lasting between 3 to 24 months, indicating that 4SCAR-T cells can exert anti-GBM activity, with a median overall survival of 10 months post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. Liu, Z., Zhou, J., Yang, X., et al.[2023]

In a study involving patients treated with GD2-targeting CAR T cells, 75% experienced both radiographic and clinical improvements, indicating a strong efficacy of this treatment approach.

The results suggest that GD2-targeting CAR T cell therapy could be a promising option for patients, potentially leading to significant positive outcomes in their cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GD2-Targeting CAR T Cells Show Promise in H3K27M-Mutated Gliomas. [2022]

CAR T cells targeting the GD2 ganglioside show promising antitumor activity against neuroblastoma, but modifications to enhance their efficacy can lead to severe central nervous system (CNS) toxicity, including neuronal destruction.

The observed CNS toxicity highlights the risks of targeting antigens like GD2 that are also present in critical normal tissues, indicating a need for strategies to manage CAR T-cell activity in the brain to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model. Richman, SA., Nunez-Cruz, S., Moghimi, B., et al.[2021]

Chimeric antigen receptor (CAR) T cells show promise in treating glioblastoma (GBM) by targeting tumor-associated antigens, offering a different mechanism of action compared to traditional therapies.

While initial clinical trials of CAR T-cell therapies for GBM showed limited benefits, further genetic modifications have significantly enhanced their anti-tumor activity in preclinical models, suggesting potential for improved outcomes in future clinical testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for glioblastoma: ready for the next round of clinical testing? Prinzing, BL., Gottschalk, SM., Krenciute, G.[2019]

GD2-targeted CAR T cells have shown promising efficacy in preclinical models of H3-K27M-mutant diffuse midline gliomas, effectively clearing tumors in five patient-derived xenograft models.

While the treatment was generally well tolerated, there were instances of neuroinflammation leading to hydrocephalus in some models, highlighting the need for careful monitoring and management in potential human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas. Mount, CW., Majzner, RG., Sundaresh, S., et al.[2022]

Murine GD2 CAR-T cells can cause severe neurotoxicity, which is influenced by the costimulatory domain used, highlighting the need for careful evaluation of CAR designs in preclinical models.

The newly developed SynNotch gated CAR-T, GD2-B7H3, shows improved efficacy and specificity against neuroblastoma in mouse models, benefiting from enhanced metabolic fitness and reduced exhaustion compared to traditional CAR-T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma. Moghimi, B., Muthugounder, S., Jambon, S., et al.[2021]

Citations

1. nature.com nature.com/articles/s41586-024-08171-9

Intravenous and intracranial GD2-CAR T cells for H3K27M ... Patients with pontine DMG (also called diffuse intrinsic pontine glioma, DIPG) have a median overall survival of 11 months from diagnosis, and 5 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04196413

GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG ... The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8967714/

GD2-CAR T cell therapy for H3K27M-mutated diffuse midline ... During cell manufacturing, patient 1 with spinal DMG experienced rapid tumour progression and was removed from the study but was treated at DL1 on a single- ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/car-t-cell-therapy-gd2-diffuse-midline-gliomas

GD2 CAR T Cells Show Promise Against DMG - NCI A CAR T-cell therapy that targets GD2 on cancer cells shrank tumors—sometimes for long periods—in children and young adults with diffuse ...

5. med.stanford.edu med.stanford.edu/news/all-news/2024/11/car-t-brain-cancer.html

Cell therapy fights lethal childhood brain cancer in Stanford ... CAR-T cells show promise against pediatric diffuse midline gliomas, brain and spinal cord tumors that are among the deadliest cancers, a Stanford Medicine ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04196413

Study Details | NCT04196413 | GD2 CAR T Cells in Diffuse ... The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults ...