Activated T Cells for Brain Cancer

Overseen By Clinical Trial Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jeremy Rudnick, M.D

Disqualifiers: Pulmonary, Cardiac, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 14

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using activated autologous T cells, a type of immunotherapy, to combat brain cancer, specifically recurrent glioblastoma. The main goal is to determine the safety of these cells and establish the maximum dosage that avoids severe side effects. The trial also seeks to understand the treatment's impact on survival and quality of life. Individuals with recurrent glioblastoma who have had their tumor completely removed and meet specific health criteria might qualify for this trial. As a Phase 1 trial, this research focuses on understanding the treatment's effects 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 activated autologous T cells are likely to be safe for humans?

Research has shown that using a person's own activated T cells may safely treat brain cancer. In several studies, researchers administered these treatments without causing serious side effects. For instance, one study found that T cells targeting brain tumor cells were well tolerated, and participants did not experience severe side effects. Another study demonstrated that using these cells to treat glioblastoma, a type of brain cancer, was safe, with no reports of serious side effects.

While these results are promising, this treatment remains in the early stages of development. Ongoing research will continue to focus on ensuring safety and determining the best dose. If considering joining a clinical trial, know that safety is a top priority in these studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about activated autologous T cells for brain cancer because they offer a new way to fight the disease by harnessing the body's own immune system. Unlike traditional treatments like surgery, radiation, or chemotherapy, which directly target cancer cells, this approach involves extracting a patient's T cells, activating them to better recognize and attack cancer cells, and then reintroducing them into the body. This personalized treatment has the potential to specifically target brain cancer cells with precision, minimizing damage to healthy tissue and potentially leading to more effective treatment outcomes.

What evidence suggests that activated T cells might be an effective treatment for brain cancer?

Research has shown that special immune cells, called activated T cells, including CAR-T cells, may help treat brain cancer. In one study, half of the patients experienced tumor shrinkage of at least 30%, and 75% had stable disease for at least two months. Another review found that tumors in the brain and spine became smaller and sometimes disappeared on scans. Animal studies demonstrated that these cells could reach brain tumors, extend survival, and even cure some mice. While more research is needed, these findings suggest that activated T cells, which participants in this trial will receive, could be effective against brain cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Jeremy D. Rudnick

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent glioblastoma who are HLA-A1 and HLA-A2 positive and have had a complete resection of their tumor. It's not suitable for those with HIV/AIDS, hepatitis B or C, allergies to DMSO or gentamicin, significant heart or lung disease, or active infections needing treatment.

Inclusion Criteria

My brain cancer has come back after treatment.

I am HLA-A1 and HLA-A2 positive.

My tumor has been completely removed surgically.

Exclusion Criteria

I am not currently being treated for an infection, but I may be taking preventive medication.

I have a history of Hepatitis B or C.

Allergy to Dimethyl sulfoxide (DMSO)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive activated autologous T cells to assess safety and tolerability

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

Post-immunotherapy infusion follow-up Day 14, and Survival follow-up Month 2

Long-term follow-up

Participants are assessed for overall response rate and tumor stem cell antigen expression

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Activated Autologous T Cells

Trial Overview The study tests the safety and tolerability of autologous activated T cells (ATCs) in patients with recurrent glioblastoma. It aims to find the maximum tolerated dose while monitoring serious adverse events and treatment-related toxicities using NCI CTCAE V5 criteria.

How Is the Trial Designed?

Group I: Activated T cells Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Jeremy Rudnick, M.D

Lead Sponsor

Trials

1

Recruited

10+

Kairos Pharma

Collaborator

Trials

1

Recruited

10+

Published Research Related to This Trial

In a study involving 15 patients with recurrent astrocytoma, researchers successfully generated and expanded tumor-specific T cells from patients' blood after immunization with their own tumor cells, demonstrating the feasibility of this approach.

The intravenous transfer of these stimulated T cells was well-tolerated with limited toxicity, paving the way for future controlled studies to evaluate the anti-tumor effects of this immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous tumor cell vaccination combined with adoptive cellular immunotherapy in patients with grade III/IV astrocytoma. Holladay, FP., Heitz-Turner, T., Bayer, WL., et al.[2019]

Adoptive transfer of ex vivo activated T lymphocytes from tumor-draining lymph nodes has shown effectiveness in treating experimental brain tumors, requiring both CD4 and CD8 T cells for optimal tumor regression.

A phase I clinical trial is underway to evaluate this T cell therapy for malignant astrocytomas, highlighting its potential as a targeted immunotherapy for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy of intracranial tumors by systemic transfer of tumor-draining lymph node cells (Review). Plautz, G., Shu, S.[2019]

Malignant central nervous system tumors are the leading cause of cancer death in children, and while treatments like surgery and chemotherapy can be effective, they often lead to significant neurological and cognitive side effects.

Adoptive cell therapy using CAR T cells shows promise for treating pediatric brain tumors, but challenges such as tumor heterogeneity and the blood-brain barrier limit its effectiveness; recent preclinical studies are exploring ways to enhance the safety and efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy's Potential for Pediatric Brain Tumors. Thomas, P., Galopin, N., Bonérandi, E., et al.[2021]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

Cellular vaccines for gliomas, including those using engineered T cells and autologous dendritic cells, have shown safety and feasibility in clinical trials, indicating they could be a promising approach for treating aggressive brain tumors like glioblastomas.

While these therapies have demonstrated some immune response activation, their overall therapeutic effects have been limited, highlighting the need for larger studies and improved guidelines to enhance their effectiveness in glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implication of cellular vaccine in glioma: current advances and future prospects. Yan, Y., Zeng, S., Gong, Z., et al.[2021]

Citations

1. nature.com nature.com/articles/s41698-024-00753-0

CAR-T cell therapy for the treatment of adult high-grade ... In this trial, half of the patients showed at least 30% tumor shrinkage and 75% of patients showed stable disease at least 2 months after CAR-T ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625001789

Review CAR T cell therapy for glioblastoma All intracranial and spinal tumors decreased in size over the treatment period, becoming unmeasurable on both MRI and positron emission ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12401244/

CAR-T cell therapy for glioblastoma: advances, challenges ... Systemic administration in vivo resulted in successful migration to brain tumors, extended survival, and cured some glioma-bearing mice.

4. nature.com nature.com/articles/s41423-024-01226-x

Immunotherapy for glioblastoma: current state, challenges ... A phase I study revealed that autologous CMV-specific T cells are safe for primary GBM patients and provide encouraging clinical evidence for ...

5. biomarkerres.biomedcentral.com biomarkerres.biomedcentral.com/articles/10.1186/s40364-024-00679-6

Advances in CAR-T therapy for central nervous system tumors The median progression-free survival (PFS) was only 1.3 months, and the median overall survival (OS) was 6.9 months [90]. This suggests the need ...

6. nature.com nature.com/articles/s41598-022-27184-w

Activated T cell therapy targeting glioblastoma cancer stem ... In this study, we demonstrated the development of autologous activated T cell therapy using three different types of antigen stimulation to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7598048/

Autologous CMV-specific T cells are a safe adjuvant ... Data presented in this study demonstrate that CMV-specific ACT can be safely used as an adjuvant therapy for primary GBM and, if offered before recurrence, this ...

8. molecular-cancer.biomedcentral.com molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01711-9

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in ... Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events.

9. trials.braintumor.org trials.braintumor.org/trials/NCT05341947

Activated Autologous T Cells Against Glioma Cancer Stem ... The purpose of this study is to examine the use of activated T cells (ATCs) to assess the safety and tolerability of autologous activated T cells, as measured ...