Adoptive Cellular Therapy for Brain Cancer

(PEACH Trial)

Recruiting at 2 trial locations

Overseen By Sharon McKee

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Giselle SaulnierSholler

Must not be taking: Investigational drugs

Disqualifiers: Autoimmune, Immunosuppressive, Organ dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and optimal dose of a new cell therapy for children with hard-to-treat brain cancers and neuroblastoma, a type of nerve cancer. It focuses on a treatment called TTRNA-xALT (Adoptive Cellular Therapy), which uses a patient's own immune cells to target cancer. The trial seeks children with newly diagnosed brain stem glioma or those with neuroblastoma who have not responded to standard treatments. Participants must be willing to undergo a biopsy to confirm their diagnosis. The trial aims to discover new ways to treat these challenging cancers. 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 therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking steroids for CNS disease, you must be on a stable dose for at least one week before the biopsy.

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

Research has shown that adoptive cellular therapy, like the one tested in this trial, is generally safe in clinical settings. This method uses the body's own cells to fight cancer. Other studies have found that treatments involving dendritic cells (a type of immune cell) loaded with tumor RNA are well-tolerated. For both diffuse intrinsic pontine glioma (DIPG) and neuroblastoma, no serious safety concerns have been reported so far.

This trial is in the early phase, focusing mainly on safety and determining the right dose. This step is crucial before progressing to larger studies that will evaluate the treatment's effectiveness. As with any early trial, there could be risks, but the goal is to find the safest way to use this new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for brain cancer, which typically involve surgery, radiation, and chemotherapy, TTRNA-xALT is a form of adoptive cellular therapy. This innovative approach uses engineered immune cells to specifically target and attack cancer cells. Researchers are excited about TTRNA-xALT because it can potentially offer a more personalized and precise treatment, minimizing damage to healthy brain tissue. Additionally, the therapy's ability to be specifically tailored to target tumor cells may increase its effectiveness against relapsed or refractory cases, offering hope where traditional treatments have failed.

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

Research has shown that adoptive cell therapy, such as TTRNA-xALT, offers a promising approach for treating challenging cancers like DIPG and neuroblastoma. In this trial, participants with DIPG will join one treatment arm, while those with neuroblastoma will join another. Early studies have found that this therapy enhances the ability of the body's immune cells, particularly T-cells, to locate and attack cancer cells more effectively. Lab studies on DIPG demonstrated potential when this method was combined with certain vaccines and chemotherapy. For neuroblastoma, using dendritic cells loaded with tumor RNA has proven generally safe and promising in clinical trials. These findings suggest that TTRNA-xALT could effectively target these difficult-to-treat cancers. ^{1 5 6 7 8}

Who Is on the Research Team?

Giselle Sholler, MD

Principal Investigator

Beat Childhood Cancer at Atrium Health

Duane Mitchell, M.D., Ph.D.

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for children with specific pediatric cancers like high-risk neuroblastoma or brain stem gliomas, who have no known effective curative therapy available. Participants must be aged ≤ 30 years, have a certain level of physical functioning (Lansky/Karnofsky Score ≥ 60), and agree to use effective birth control. They should not have significant organ dysfunction or other serious medical conditions that could affect the study.

Inclusion Criteria

Informed Consent: All subjects and/or legal guardians must sign informed written consent

I am over 12 months old with neuroblastoma.

Women who could become pregnant need to have a negative pregnancy test.

Exclusion Criteria

My biopsy did not show cancer or showed a type other than neuroblastoma or glioma.

Subjects with any other medical condition deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study

Subjects receiving any investigational drug concurrently

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive molecular targeted therapy in combination with adoptive cell therapy, including TTRNA-DCs, TTRNA-xALT, and autologous G-CSF mobilized HSCs

2 years

Follow-up

Participants are monitored for safety, effectiveness, and overall survival after treatment

7 years

Dose Escalation

A standard 3+3 dose escalation design to establish the maximum tolerated dose (MTD) with three pre-specified dose levels of xALT

What Are the Treatments Tested in This Trial?

Interventions

• TTRNA-xALT

Trial Overview The PEACH TRIAL tests a combination of molecular targeted therapy with adoptive cell therapy in children with newly diagnosed DIPG or recurrent neuroblastoma. It aims to find the safest dose for treatments involving autologous dendritic cells, lymphocyte transfer, and hematopoietic stem cells.

How Is the Trial Designed?

Group I: Arm 2: Relapsed/Refractory Neuroblastoma (NB) Experimental Treatment 1 Intervention

This Phase I study is will utilize a standard 3+3 dose escalation design to establish the MTD and will evaluate the following three pre-specified dose levels of xALT: Dose Level 1: 3 x10\^7 cells/kg Dose Level +1: 3 x10\^8 cells/kg Dose Level -1: 3 x10\^6 cells/kg The dose escalation scheme will be evaluated for Arm 1 and Arm 2 separately. For each Study Arm, a minimum of 4 DLT evaluable subjects and a maximum of 12 DLT evaluable subjects will be enrolled (a total of 8 to 24 DLT evaluable subjects).

Group II: Arm 1: Subjects with Diffuse Intrinsic Pontine Glioma (DIPG). Experimental Treatment 1 Intervention

This Phase I study is will utilize a standard 3+3 dose escalation design to establish the MTD and will evaluate the following three pre-specified dose levels of xALT: Dose Level 1: 3 x10\^7 cells/kg Dose Level +1: 3 x10\^8 cells/kg Dose Level -1: 3 x10\^6 cells/kg The dose escalation scheme will be evaluated for Arm 1 and Arm 2 separately. For each Study Arm, a minimum of 4 DLT evaluable subjects and a maximum of 12 DLT evaluable subjects will be enrolled (a total of 8 to 24 DLT evaluable subjects).

Who Is Running the Clinical Trial?

Giselle SaulnierSholler

Lead Sponsor

Trials

22

Recruited

2,400+

Giselle Sholler

Lead Sponsor

Trials

23

Recruited

2,500+

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Beat Childhood Cancer Research Consortium

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Using RNA derived from small tumor cells to generate cytotoxic T lymphocytes (CTLs) is a promising method, as it allows for the creation of effective antigen-presenting cells (APCs) without needing large amounts of tumor cells.

The study demonstrated that amplified tumor RNA can be successfully introduced into dendritic cells and EBV-transformed B cells, leading to the generation of polyclonal polyspecific CTLs, which could enhance the effectiveness of cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor RNA introduction into dendritic cells and Epstein-Barr virus transformed B cells]. Minami, K., Yamaguchi, Y., Ohshita, A., et al.[2006]

A new method using total tumor RNA to prime dendritic cells for generating anti-tumor T cells shows promise in creating effective treatments for cancers, including brain tumors.

The study found that using a specific cytokine cocktail, rather than IL-2, enhanced the generation of T cells with high CD62L levels, which are better at recognizing and attacking tumor cells, leading to improved anti-tumor efficacy in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model. Yang, S., Archer, GE., Flores, CE., et al.[2021]

The phase 1 study involving 9 pediatric patients demonstrated that the DCRNA vaccine, made from monocyte-derived dendritic cells pulsed with tumor RNA, is both safe and feasible for treating recurrent brain tumors.

After receiving the DCRNA vaccine, 2 out of 7 patients showed stable disease, and 1 patient had a partial response, indicating potential effectiveness in eliciting tumor-specific immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer. Caruso, DA., Orme, LM., Neale, AM., et al.[2020]

Adoptive cellular therapy (ACT) using tumor RNA-pulsed dendritic cells successfully expanded tumor-reactive T lymphocytes, leading to effective treatment in a model of malignant glioma, which is typically resistant to conventional therapies.

Hematopoietic stem cells (HSCs) not only supported recovery from myeloablative conditioning but also enhanced the immune response against tumors, suggesting a new role for HSCs in improving outcomes for patients with solid tumors like gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel role of hematopoietic stem cells in immunologic rejection of malignant gliomas. Flores, C., Pham, C., Snyder, D., et al.[2021]

Dendritic cell (DC) vaccination has been proven safe in clinical trials involving 781 patients with various cancers and HIV, showing no significant short or long-term side effects.

Using mRNA to load DCs with tumor antigens enhances their ability to stimulate the immune system, and this method allows for targeted treatment across a wide range of tumor types, including melanoma and pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Cancer Vaccination with Ex Vivo RNA-Transfected Dendritic Cells-An Update. Dörrie, J., Schaft, N., Schuler, G., et al.[2020]

The study developed RNA-nanoparticles (NPs) using the cationic lipid DOTAP, which effectively deliver tumor-derived RNA to antigen-presenting cells (APCs), leading to systemic activation of the immune response.

RNA-NPs significantly enhance the expression of key activation markers on APCs and induce a stronger expansion of antigen-specific T-cells compared to traditional peptide vaccines, demonstrating their potential as a more effective immunotherapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles. Sayour, EJ., De Leon, G., Pham, C., et al.[2021]

The study developed an adoptive cellular therapy using dendritic cells loaded with tumor RNA to stimulate T cells that target multiple antigens in brain tumors like medulloblastoma and glioblastoma.

In both preclinical models and a patient case, successful therapy was marked by a significant expansion and long-term presence of tumor-specific T cells in the blood, indicating a strong immune response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy. Flores, C., Wildes, T., Dean, BD., et al.[2023]

Dendritic cell (DC) vaccination using G422 glioblastoma RNA significantly increased the survival duration of mice with glioblastomas, indicating its potential as an effective anti-tumor treatment.

The treatment led to increased levels of the cytokine IFN-gamma and decreased levels of IL-10, suggesting an enhanced immune response against the tumor, along with evidence of tumor necrosis in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dendritic cells pulsed with glioma RNA induce immunity against intracranial gliomas]. Yu, JB., Feng, ZX., Zhan, RY.[2022]

The study evaluated a novel cancer vaccine using autologous dendritic cells (DCs) transfected with patient-specific tumor mRNA, aiming to present a wide range of unique tumor antigens for each individual, which could enhance the vaccine's effectiveness.

In vitro tests showed that the transfected DCs successfully generated specific T-cell responses in all six patients tested, indicating the potential for this personalized approach to stimulate the immune system against malignant melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical full-scale evaluation of dendritic cells transfected with autologous tumor-mRNA for melanoma vaccination. Kyte, JA., Kvalheim, G., Aamdal, S., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04837547?cond=Diffuse%20intrinsic%20pontine%20glioma%20OR%20%22DIPG%22&aggFilters=status:not%20rec&viewType=Table&rank=5

Precision Medicine and Adoptive Cellular Therapy The first product will be autologous dendritic cells (DCs) loaded with total tumor messenger ribonucleic acid (mRNA) (TTRNA) derived from malignant tumors. The ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5475097/

DIPG-23. PHASE I STUDY OF ADOPTIVE CELLULAR ... Based on lab studies demonstrating efficacy of x-ALT + ttRNA-DC vaccine +HSC following DI chemotherapy in DIPG models, we plan to conduct a study of this ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-02444

Adoptive Cell Therapy (TTRNA-xALT), Dendritic ... This phase I trial tests the safety, side effects, and effectiveness of adoptive cell therapy (ACT) with total tumor messenger ribonucleic acid (mRNA)-pulsed ...

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

Adoptive Cellular Therapy for Brain Cancer (PEACH Trial) Research shows that adoptive cellular therapy, including methods using dendritic cells pulsed with tumor RNA, has been generally safe in clinical trials for ...

5. jitc.bmj.com jitc.bmj.com/content/13/6/e012009

Exploring the tumor microenvironment in diffuse intrinsic ... Diffuse intrinsic pontine glioma (DIPG) is a rare and highly aggressive pediatric brain tumor with a median survival of less than 12 months.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02840123

Safety Study of DIPG Treatment With Autologous Dendritic ... There are three types of violations: Failure to submit required clinical trial information; Submission of false or misleading clinical trial information ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9512276/

Clinical advances and ongoing trials of mRNA vaccines for ... This Review summarises the latest clinical advances in mRNA-based vaccines for cancer treatment and reflects on future perspectives and challenges

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11106442/

Current immunotherapeutic approaches to diffuse intrinsic ... Benitez-Ribas et al. (2018) also published preliminary results demonstrating the safety of autologous dendritic cells pulsed with tumour lysates ...