Vaccine Immunotherapy for Pediatric Brain Cancer

(Re-MATCH Trial)

No longer recruiting at 3 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Immunosuppressants, Anticancer drugs

Disqualifiers: Pregnancy, Active infection, Immunosuppressive disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if tumor-specific immune cells and dendritic cell vaccines can improve outcomes for children with recurring brain tumors, specifically medulloblastoma or supratentorial primitive neuroectodermal tumors. Participants are divided into two groups, both receiving chemotherapy and a stem cell transplant, followed by the experimental vaccines TTRNA-DCs and TTRNA-xALT (Total tumor mRNA-pulsed autologous Dendritic Cells with Tumor-specific ex vivo expanded autologous lymphocyte transfer). This trial suits children and young adults who have experienced their first recurrence of these brain tumors after radiation treatment and have stable neurological symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking immunosuppressive agents or any other anticancer or investigational drug therapy.

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

Research shows that the treatments studied in this trial have generally been safe in earlier studies. The use of dendritic cells, which are special immune cells, combined with tumor RNA (TTRNA-DCs), has proven to be safe and practical. This method may help patients by potentially slowing tumor growth.

In other studies, adoptive cellular therapy, which includes these dendritic cells, has been well-tolerated by patients. Similarly, TTRNA-xALT uses a method with cells that target tumors. Research indicates this approach has also been safe in trials for brain cancer.

Both treatments have undergone testing in people before, and evidence suggests they are safe for human use. However, like any treatment, side effects can occur, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TTRNA-xALT and TTRNA-DCs for pediatric brain cancer because they offer a novel approach to immunotherapy. Unlike traditional treatments like surgery, radiation, and chemotherapy, these investigational treatments use tumor-specific RNA to activate the immune system, potentially leading to a more targeted attack on cancer cells. This mechanism could minimize damage to healthy cells, reducing side effects. Additionally, combining these treatments with high-dose chemotherapy and stem cell transplants might enhance their effectiveness, offering hope for improved outcomes in a challenging condition to treat.

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

This trial will evaluate two experimental treatment groups for pediatric brain cancer. Group A will receive high-dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. Group B will receive NMA salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

Studies have shown that immunotherapy, which uses the body's immune system to fight cancer, can be promising for treating brain tumors. Research on TTRNA-DCs, a type of cell therapy, has demonstrated their ability to grow T cells, which are crucial for fighting tumors. In some studies, patients experienced tumor shrinkage and a stronger immune response. TTRNA-xALT, another cell therapy, also uses the body's own immune cells to attack tumors and has shown potential in boosting the body's defense against cancer. Early results suggest these treatments might help manage recurring brain tumors in children by enhancing the immune system's ability to fight cancer cells. ^{1 2 5 6 7}

Who Is on the Research Team?

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 up to 30 years old with a first recurrence of medulloblastoma or primitive neuroectodermal tumors after radiotherapy. Participants need stable neurological function, adequate blood counts, normal kidney and liver function, and must agree to use birth control. Those with genetic risks for radiation-induced cancers are also eligible.

Inclusion Criteria

I am 30 years old or younger.

Patients must have ANC ≥ 1000/µl, Platelets ≥ 100,000/µl, Hemoglobin > 8 g/dL, Serum creatinine ≤ upper limit of institutional normal, Bilirubin ≤ 1.5 times upper limit of normal for age, ALT ≤ 3 times institutional upper limit of normal for age, AST ≤ 3 times institutional upper limit of normal for age

Signed informed consent according to institutional guidelines must be obtained prior to registration

Exclusion Criteria

I do not have HIV, Hepatitis B or C, or any known immunosuppressive disease.

Patients receiving any other concurrent anticancer or investigational drug therapy

Patients with any clinically significant unrelated systemic illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Resection/Biopsy

Surgical resection, biopsy, or cytology examination with confirmatory pathologic diagnosis

1-2 weeks

Chemotherapy and Stem Cell Transplantation

High dose or non-myeloablative chemotherapy followed by peripheral blood stem cell transplant

4-6 weeks

Immunotherapy

Administration of TTRNA-xALT and TTRNA-loaded dendritic cell vaccines

6 weeks

Weekly visits for 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• TTRNA-DCs
• TTRNA-xALT

Trial Overview The study tests tumor-specific immune cells (TTRNA-xALT) and dendritic cell vaccines (TTRNA-DCs) on about 35 patients with recurrent brain tumors. It aims to see how these immunotherapies affect the tumor's progression based on prior success in adult cancer treatments.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 2 Interventions

NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

Group II: Group A Experimental Treatment 2 Interventions

High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Citations

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

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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1872001/

Results of a phase 1 study utilizing monocyte-derived ... One of 10 patients showed significant tumor regression, 3 of 7 patients showed tumor-specific IFN-γ production, and 3 of 6 showed delayed-type hypersensitivity ...

3. withpower.com withpower.com/trial/phase-1-glioma-8-2021-fb81e

Adoptive Cellular Therapy for Brain Cancer (PEACH Trial) Adoptive cellular therapy (ACT) using tumor RNA-pulsed dendritic cells successfully expanded tumor-reactive T lymphocytes, leading to effective treatment in a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12239805/

Updates on cancer vaccines in brain cancer - PubMed Central A phase I/II trial comparing autologous dendritic cell vaccine pulsed either with personalized peptides (PEP-DC) or with tumor lysate (OC-DC) ...

5. apps.dtic.mil apps.dtic.mil/sti/tr/pdf/ADA551893.pdf

Adoptive Cellular Therapy Targeting Recurrent Pediatric Brain ... This prospective Phase I/II clinical trial will evaluate the safety of autologous TTRNA. mRNA-loaded T-cell immunotherapy in conjunction with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04911621

Study Details | NCT04911621 | Adjuvant Dendritic Cell ... A clinical study including 10 pediatric patients (aged ≥ 12 months and < 18 years at the time of signing the informed consent) with brain (stem) tumors is ...

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 ...