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

11 Participants Needed

Trial Summary

What is the purpose of this trial?

The standard of care for children with DIPG includes focal radiotherapy (RT) but outcomes have remained dismal despite this treatment. The addition of oral Temozolomide (TMZ) concurrently with RT followed by monthly TMZ was also found to be safe but ineffective. Recent studies in adults have shown that certain types of chemotherapy induce a profound but transient lymphopenia (low blood lymphocytes) and vaccinating and/or the adoptive transfer of tumor-specific lymphocytes into the cancer patient during this lymphopenic state leads to dramatic T cell expansion and potent immunologic and clinical responses. Therefore, patients in this study will either receive concurrent TMZ during RT and immunotherapy during and after maintenance cycles of dose-intensive TMZ (Group A) or focal radiotherapy alone and immunotherapy without maintenance DI TMZ (Group B). Immune responses during cycles of DC vaccination with or without DI TMZ will be evaluated in both treatment groups.

Research Team

Elias Sayour, MD, PhD

Principal Investigator

University of Florida

Eligibility Criteria

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

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

My brain tumor has been confirmed by a biopsy.

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

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

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

Treatment Details

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.

Participant Groups

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+