Adoptive Cellular Therapy for Brain Cancer

(ACTION Trial)

No longer recruiting at 3 trial locations
MH
JK
Overseen ByJennifer King, RN
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: University of Florida
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for high-grade gliomas, an aggressive brain cancer. Researchers aim to determine if specially made vaccines, known as TTRNA-DC vaccines with GM-CSF (Total Tumor RNA-pulsed Dendritic Cell vaccines with Granulocyte-Macrophage Colony-Stimulating Factor), can activate the body's T-cells to attack and destroy tumor cells in the brain. The trial includes two groups, each receiving slightly different combinations of the vaccine and other supportive treatments. Individuals diagnosed with high-grade glioma and planning to undergo tumor-removal surgery might be suitable for this study. 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 new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if 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 trial's treatments are likely to be safe?

Research shows that the dendritic cell (DC) vaccines and adoptive lymphocyte transfer (ALT) therapies studied in this trial have been safe in past studies. These treatments aim to strengthen the body's immune system to better identify and destroy tumor cells.

For the TTRNA-DC vaccines with GM-CSF, studies have shown that this method is generally safe for patients with glioblastoma, a type of brain cancer. The vaccines use dendritic cells to activate T-cells, which are immune cells that can fight cancer. Past research found that these vaccines did not cause serious side effects and were well-tolerated by patients.

Similarly, TTRNA-xALT therapy, which boosts T-cells to better target tumors, has also been studied for safety. Research shows that this method is generally safe and does not lead to severe adverse events. This treatment uses T-cells trained to recognize and attack cancer cells, strengthening the immune response.

This trial is in an early phase, focusing on ensuring these treatments are safe for people. While previous studies have shown safety, this trial will help confirm that they are safe and can stimulate the immune system to fight brain tumors.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain cancer because they use TTRNA-DC vaccines with GM-CSF and TTRNA-xALT, which are designed to train the immune system to recognize and attack cancer cells more effectively. Unlike standard treatments like surgery, radiation, and chemotherapy, these therapies harness the body's immune response, offering a potentially more targeted approach. One unique feature is the use of Autologous Hematopoietic Stem Cells (HSCs) in Group B, which could enhance recovery and immune system function after treatment. This innovative approach could lead to more effective and personalized cancer care, with the potential for fewer side effects compared to traditional treatments.

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

Research has shown that dendritic cell (DC) vaccines can help the immune system attack tumors. These vaccines use the complete genetic material from tumors to train DCs to recognize and fight cancer cells. In this trial, participants in both Group A and Group B will receive TTRNA-DC vaccines with GM-CSF and TTRNA-xALT. Studies have found that combining this method with adoptive cell therapy (ACT) can increase the number of T-cells that specifically target and destroy tumor cells, even in challenging brain cancers like high-grade gliomas. Early results suggest that this approach might help the immune system overcome obstacles like the blood-brain barrier, which often protects brain tumors. While researchers are still testing this treatment for safety and effectiveness, it shows promise in boosting the body's natural defenses against cancer.35678

Who Is on the Research Team?

Elias Sayour, MD, PhD » Lillian S ...

Elias Sayour, MD, PhD

Principal Investigator

University of Florida

DM

Duane Mitchell, MD, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for pediatric patients with high-grade gliomas who are scheduled for tumor removal surgery. They must have a certain level of physical function, normal kidney and liver tests, and agree to use birth control. It's not open to those with autoimmune diseases, HIV, severe medical conditions, or pregnant/breastfeeding individuals.

Inclusion Criteria

Signed informed consent according to institutional guidelines
Bone Marrow: ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported); Platelets ≥ 100,000/µl (unsupported for at least 3 days); Hemoglobin > 8 g/dL (may be supported)
I am mostly able to care for myself and carry out daily activities.
See 7 more

Exclusion Criteria

I have an autoimmune disease, immunosuppression, or HIV.
I do not have major heart, kidney, liver, lung, or other organ problems.
Prior allergic reaction to TMZ, GM-CSF, or Td
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive dose-intensified temozolomide with TTRNA-DC vaccines and GM-CSF

10 months

Immunotherapy

Participants receive TTRNA-xALT vaccine and Td vaccine, with or without autologous hematopoietic stem cells

10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 years

What Are the Treatments Tested in This Trial?

Interventions

  • TTRNA-DC vaccines with GM-CSF
  • TTRNA-xALT
Trial Overview The study is testing whether vaccines made from a patient's own tumor can stimulate the immune system to fight brain tumors in children. It involves creating T-cell and Dendritic Cell (DC) vaccines that aim to activate the body’s natural defenses against aggressive brain cancer.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Group BExperimental Treatment5 Interventions
Group II: Group AExperimental Treatment4 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials
1,428
Recruited
987,000+

National Pediatric Cancer Foundation

Collaborator

Trials
8
Recruited
300+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Moffitt Clinical Research Network (MCRN)

Collaborator

Trials
1
Recruited
20+

National Institutes of Health (NIH)

Collaborator

Trials
2,896
Recruited
8,053,000+

Citations

Dendritic Cell Vaccination of Glioblastoma: Road to Success ...Here, we discuss the results of recent vaccination trials, relevant parameters of the vaccines themselves and of their application, and possible synergies ...
Total tumor RNA pulsed dendritic cells plus adoptive ...The focus of this review is our experience in using adoptive lymphocyte transfer (ALT) with total tumor derived mRNA loaded dendritic cells (DCs) following ...
RNA-Modified T Cells Mediate Effective Delivery of ...With the presence of the blood-brain barrier (BBB), successful immunotherapeutic drug delivery to CNS malignancies re- mains a challenge.
Dendritic cell immunotherapy advances for solid tumorsDC-based immunotherapy has been investigated for over two decades, aiming to induce anti-tumor immunity by directly delivering DCs or antigens ...
A Personalized Vaccine (TTRNA-DCs & TTRNA-xALT) for ...This phase I trial studies the safety and side effects of a personalized vaccine (total tumor messenger ribonucleic acid [mRNA]-pulsed autologous dendritic ...
Dendritic cell vaccination for glioblastoma multiforme patientsThe vehicle can be a simple solution, strengthened with danger signals such as poly I:C, montanide, or granulocyte-macrophage colony-stimulating factor (GM-CSF) ...
Translational advancements in tumor vaccine therapies for ...Vaccines are a promising treatment for glioblastoma. Personalized vaccines and combination therapy might enhance efficacy. Gliomas are the most ...
Optimizing T Cell-Based Therapy for GlioblastomaThis review will discuss adoptive T cell transfer strategies and methods to avoid T cell dysfunction for the treatment of brain cancer. Keywords ...
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