Adoptive T Cell Therapy and Vaccines for Medulloblastoma

(MATCHPOINT Trial)

Overseen By Marcia Hodik, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis, Autoimmune, Pregnancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 3-6 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for children and young adults with medulloblastoma that has returned or worsened. It tests the safety and feasibility of a therapy using the body's own cells to fight cancer, combined with pembrolizumab, a drug that helps the immune system target cancer cells. The trial also includes TTRNA-DC vaccines and TTRNA-xALT, which are part of the adoptive T cell therapy approach. Suitable candidates for this trial are those whose medulloblastoma has returned or worsened after radiation and who are eligible for surgery or have stored tumor tissue available for study use. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take corticosteroids equivalent to 4mg or more of dexamethasone daily. 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 pembrolizumab, a drug used in immunotherapy, is generally well-tolerated. One study noted a few serious side effects, such as skin rash, low red blood cell count (anemia), and low white blood cell count (neutropenia), but these were uncommon and did not limit the dosage. This suggests that while some risks exist, they can be managed.

For the TTRNA-DC vaccines, research has shown they are both practical and safe. Earlier studies reported no major safety issues in patients, suggesting these vaccines are likely to be well-tolerated.

Early research on adoptive cell therapy (ACT) with TTRNA-xALT also shows it is safe, with no severe side effects reported. This indicates that while it is still being tested, it seems safe for humans so far.

Overall, these treatments undergo careful safety testing. While some side effects might occur, they appear relatively minor and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for medulloblastoma, which often involve surgery, radiation, and chemotherapy, this innovative therapy combines adoptive cellular therapy (ACT) with pembrolizumab, a PD-1 blocking antibody. This approach is unique because it uses tumor-reactive lymphocytes expanded outside the body and a tumor RNA-pulsed dendritic cell (DC) vaccine to target the cancer more precisely. Pembrolizumab enhances this process by inhibiting the PD-1 pathway, potentially leading to a stronger immune response against the tumor. Researchers are excited because this treatment could offer a more targeted and effective attack on cancer cells, potentially improving outcomes for patients with medulloblastoma.

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

Research has shown that adoptive cellular therapy (ACT), when combined with pembrolizumab, may help treat medulloblastoma, a type of brain cancer. In this trial, participants will receive ACT combined with PD-1 blockade using pembrolizumab. This treatment uses the body's own immune cells, modified and grown outside the body, to target and attack cancer cells. Studies have found that these therapies together enhance the immune system's ability to identify and fight tumors. In early tests, this combination improved the ability to destroy cancer cells. Although medulloblastomas have low levels of certain immune signals, adding pembrolizumab can enhance ACT by overcoming these challenges. Early results in other cancers suggest this combination could offer new hope for hard-to-treat tumors like medulloblastoma. ^{1 4 6 7 8}

Who Is on the Research Team?

John Ligon, MD

Principal Investigator

University of Florida

Duane Mitchell, MD, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 4-30 with a specific type of brain cancer called Group 3 or 4 medulloblastoma that has come back after treatment. They must be able to undergo surgery, have a certain level of physical function, and their major organs need to work well. Those with genetic conditions increasing cancer risk from radiation can join at first recurrence.

Inclusion Criteria

My hemoglobin level is at least 9 g/dL.

I can care for myself but may not be able to do active work or play.

My white blood cell count is at least 1,000 without support.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgery and Initial Treatment Preparation

Participants undergo tumor resection or biopsy, collection of PBMCs for DC generation, and initiation of salvage chemotherapy

4-6 weeks

Multiple visits (in-person) for surgery and chemotherapy initiation

Treatment

Participants receive TTRNA-DC vaccines, undergo leukapheresis for T cell expansion, and continue with salvage chemotherapy

3-6 months

Bi-weekly and monthly visits for vaccines and chemotherapy

Adoptive Cellular Therapy (ACT)

Participants receive non-myeloablative conditioning, infusion of expanded lymphocytes, HSCs, and PD-1 blockade

2 weeks

In-person visits for conditioning and infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• TTRNA-DC vaccines
• TTRNA-xALT

Trial Overview The study tests a combination therapy in patients with relapsed medulloblastoma: adoptive T cell therapy, dendritic cell vaccines mixed with GM-CSF, hematopoietic stem cells transplant, and Pembrolizumab (an immune checkpoint inhibitor). It's designed to see if this approach is feasible and safe.

How Is the Trial Designed?

Group I: Adoptive Cellular Therapy (ACT) + PD-1 blockade with pembrolizumab Experimental Treatment 5 Interventions

ACT + PD-1 blockade consists of the intravenous delivery of ex vivo expanded tumor-reactive lymphocytes and autologous hematopoietic stem cells (HSCs) with concomitant tumor RNA-pulsed DC vaccines followed by intravenous delivery of PD-1 blocking antibodies.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06514898

NCT06514898 | Adoptive T Cell Therapy, DC Vaccines ... This is a single-site, single arm, unblinded, uncontrolled pilot study to evaluate the feasibility and safety of ACT + PD-1 blockade in children and young ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8582409/

Immunotherapy in Medulloblastoma: Current State of ... CAR T-cell therapy is a novel, promising type of adoptive cell ... PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0035378725005557

Literature review: CAR T-cell therapy as a promising ... Combining these CAR T-cells with PD-1 blockade enhanced efficacy in tumour-bearing mice. Overall, both CAR T-cell types eliminated 20%–50% of GBM in ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/2162402X.2017.1398877

Prognostic relevance of tumor-infiltrating lymphocytes and ... We found limited numbers of PD1+ T-cells and complete absence of PD-L1 on medulloblastomas. Medulloblastomas downregulated immune recognition molecules MHC-I ...

5. withpower.com withpower.com/trial/phase-1-recurrent-group-4-non-shhnon-wnt-medulloblastoma-8-2024-caa01

Adoptive T Cell Therapy and Vaccines for Medulloblastoma This is a pilot study in a small number of children and young adults with relapsed/progressive medulloblastoma (MB) looking at the feasibility and safety of ...

6. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii85/7890049

CTIM-06. OUTCOME OF PATIENTS WITH RECURRENT ... Grade 3 or greater treatment-related adverse events included rash (n=1), anemia (n=1) and neutropenia (n=2), with no dose-limiting toxicities.

7. pbtc.org pbtc.org/public/Summaries/PBTC-045/045%20Abstract%20and%20Schema%20for%20Professionals.pdf

PBTC-045: A Safety and Preliminary Efficacy trial of MK- ... The primary endpoints for the first phase of the study will be toxicity and safety monitoring of Pembrolizumab (MK3475), and for the second phase of the study ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ped4.12261

Immune cell landscape and immunotherapy of ... It has been demonstrated that PD-1 blockade can result in a more effective outcome in group 3 than that in SHH medulloblastomas.