Immunotherapy + Radiotherapy for Brain Stem Glioma

(BRAVO Trial)

Overseen By Marcia Hodik, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Corticosteroids, Anticancer drugs, others

Disqualifiers: Autoimmune disease, Organ dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for brain stem glioma, a challenging type of brain cancer. Researchers are testing a combination of radiotherapy and immunotherapy, which harnesses the body's immune system to fight cancer, to determine if it can improve outcomes. Participants will receive either a combination of chemotherapy (Temozolomide) and immunotherapy (including TTRNA-DC vaccines with GM-CSF and TTRNA-xALT) or just immunotherapy following radiotherapy. Those diagnosed with diffuse intrinsic pontine glioma (DIPG), who have a stable post-surgical condition and are willing to consent to a biopsy, are well-suited for this trial. 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 innovative treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take other anticancer or investigational drugs during the study.

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

Research has shown that dendritic cell (DC) vaccines, such as TTRNA-DC vaccines with GM-CSF, may aid in treating various cancers. These vaccines introduce cells that can combat cancer, assisting the immune system in targeting tumors. Studies have found that these treatments can sometimes extend the lives of individuals with certain blood cancers.

For TTRNA-xALT, research indicates that this method employs specially prepared immune cells to locate and attack cancer cells. Although still under investigation, these treatments aim to enhance the body's natural tumor-fighting abilities.

Both TTRNA-DC vaccines and TTRNA-xALT have undergone clinical trials with some positive outcomes. However, as this study is in its early stages, it primarily focuses on assessing safety. While other trials suggest these treatments can be safe, researchers continue to monitor closely for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the TTRNA-DC vaccines with GM-CSF and TTRNA-xALT treatments because they offer a novel approach to tackling brain stem glioma, a tough-to-treat cancer. Unlike standard treatments like radiation and chemotherapy, these vaccines harness the body's immune system to fight the tumor, potentially improving precision and effectiveness. Group A combines this immunotherapy with dose-intensified temozolomide (TMZ) and autologous hematopoietic stem cells, while Group B pairs it with cyclophosphamide and fludarabine lymphodepletive conditioning. This innovative approach aims to enhance the body's ability to target and destroy cancer cells, offering hope for better outcomes.

What evidence suggests that this trial's treatments could be effective for brain stem glioma?

Research has shown that TTRNA-DC vaccines with GM-CSF, a treatment in this trial, can help the immune system fight tumors by teaching the body to identify and attack cancer cells. Studies have found that these vaccines can generate strong immune responses in brain tumors. Another treatment option in this trial, TTRNA-xALT, uses specially prepared immune cells to target cancer cells. Early results suggest these treatments can enhance the immune system's ability to fight cancer. While these methods appear promising, further research is needed to confirm their effectiveness for brain stem gliomas. ^{2 4 6 7 8}

Who Is on the Research Team?

Elias Sayour, MD, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for children with a specific brain tumor called DIPG or other diffuse intrinsic brain stem gliomas. They must be stable after surgery, have certain blood and organ function levels, and agree to use birth control if applicable. Those with severe allergies to the drugs used in this study, significant organ dysfunction, unstable medical conditions, or who cannot follow the study procedures are not eligible.

Inclusion Criteria

Patients of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control while being treated on this study

My brain tumor is a high-grade stem glioma confirmed by imaging.

My brain tumor has been confirmed by a biopsy.

Exclusion Criteria

Patients who are unwilling or unable to receive treatment and undergo follow-up evaluations at University of Florida

I have severe swallowing difficulties, reduced consciousness, or paralysis in all four limbs.

My biopsy did not show any cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive focal radiotherapy, with Group A receiving concurrent Temozolomide

6 weeks

Weekly visits for radiation sessions

Immunotherapy

Participants receive TTRNA-DC vaccines and adoptive cellular therapy, with Group A receiving dose-intensified Temozolomide

10 months

Monthly visits for DC vaccination and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide + Fludarabine Lymphodepletive Conditioning
• Dose-Intensified TMZ
• TTRNA-DC vaccines with GM-CSF
• TTRNA-xALT

Trial Overview The trial tests two approaches for treating brain tumors: Group A gets radiotherapy plus chemotherapy (TMZ) and immunotherapy; Group B gets only radiotherapy followed by immunotherapy. The focus is on how well patients respond to immune system-boosting treatments during and after these therapies.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 5 Interventions

TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) with Cyclophosphamide + Fludarabine Lymphodepletive Conditioning

Group II: Group A Experimental Treatment 5 Interventions

TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) during cycles of Dose-intensified TMZ

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Lyla Nsouli Foundation

Collaborator

Trials

1

Recruited

10+

Accelerate Brain Cancer Cure

Collaborator

Trials

4

Recruited

550+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12418593/

Translational advancements in tumor vaccine therapies for ... Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate‐pulsed dendritic cells in a murine glioma model.

2. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/total-tumor-rna-loaded-dendritic-cell-vaccine?pn=1

Clinical Trials Using Total Tumor RNA-loaded Dendritic ... Review the clinical trials studying total tumor rna-loaded dendritic cell vaccine on this list and use the filters to refine the results by age and location ...

3. withpower.com withpower.com/trial/phase-1-recurrent-oligodendroglioma-3-2024-04e19

Cellular Therapy for Brain Tumors (ADAGiO Trial) Trial Overview The study tests adoptive cellular therapy, which includes TTRNA-DC vaccines with GM-CSF, autologous hematopoietic stem cells (HSCs), TTRNA-xALT, ...

4. oaepublish.com oaepublish.com/articles/2347-8659.2018.44

Total tumor RNA pulsed dendritic cells plus adoptive ... Our lab has expertise in the development of ex vivo “educated” adoptive T-cell transfer along with total tumor RNA (ttRNA) DC vaccines for the treatment of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666379125004859

Dendritic cell immunotherapy advances for solid tumors DC-based immunotherapy has been investigated for over two decades, aiming to induce anti-tumor immunity by directly delivering DCs or antigens ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6453546/

RNA-Modified T Cells Mediate Effective Delivery ... Using T cell mRNA electroporation, we demonstrated that activated T cells can be modified to secrete granulocyte macrophage colony-stimulating factor (GM-CSF) ...

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/C155969

Clinical Trials Using Total Tumor mRNA-pulsed ... Review the clinical trials studying total tumor mrna-pulsed tumor-specific ex vivo-expanded autologous lymphocyte transfer cells on this list and use the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10547519/

Dendritic cell vaccine trials in gliomas: Untangling the lines Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies.