Adoptive Cellular Therapy for Pediatric Brain Tumors

(IMPACT Trial)

Recruiting at 1 trial location

Overseen By Fahmida Hoq, MBBS

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's National Research Institute

Must not be taking: ATG, Campath, others

Disqualifiers: Uncontrolled infections, HIV, bulky tumors, others

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for children under 5 with specific brain tumors who often cannot receive radiation due to harmful side effects. The treatment uses the patient’s own cells, modified to target and fight their unique cancer cells. Known as Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T), this approach is for children diagnosed with aggressive brain tumors like medulloblastoma or similar conditions who have undergone standard treatment. Participants should have stable health conditions and no recent infections. The goal is to determine if this approach is safe and effective in combating these challenging tumors. 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 does not specify if you need to stop taking your current medications. However, you cannot have received certain immunotherapy treatments within 28 days before the trial, and you must be on a stable or decreasing dose of steroids before receiving the TSA-T cells.

What prior data suggests that this adoptive cellular therapy is safe for pediatric brain tumors?

Research shows that a new treatment using special immune cells, called TSA-T, has been tested in early studies for treating children's brain tumors. These studies primarily assess the treatment's safety and practicality. Detailed information about side effects is not yet available, as this is a phase 1 trial—the initial stage of testing new treatments in people. The primary goal at this stage is to ensure safety and identify any side effects. While the treatment appears promising, researchers are still learning about all the possible reactions it might cause. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for brain tumors?

Most treatments for pediatric brain tumors involve surgery, radiation, or chemotherapy. However, TSA-T therapy is unique because it uses the body's own immune system to fight the cancer. It involves engineering cytotoxic T lymphocytes to specifically target and destroy tumor cells based on their unique antigens. This approach is promising because it aims to precisely attack cancer cells while sparing healthy ones, potentially reducing side effects compared to traditional therapies. Researchers are excited about this treatment as it represents a cutting-edge, personalized strategy that could improve outcomes for young children with high-risk brain tumors.

What evidence suggests that this treatment might be an effective treatment for pediatric brain tumors?

Research shows that a new type of immune cell treatment, called TSA-T, could bring new hope for treating brain tumors in children. In this trial, participants will receive TSA-T, which uses special immune cells designed to find and attack cancer cells by recognizing unique markers on the tumor. Studies suggest that TSA-T can enhance the body's natural ability to fight cancer by focusing on these specific targets. Unlike traditional treatments like chemotherapy and radiation, which can be tough on young children, TSA-T aims to be more precise. Early results have shown promise in helping patients with hard-to-treat brain tumors. This innovative treatment offers a potential new way to tackle these challenging conditions. ^{1 3 4 5 6}

Who Is on the Research Team?

Eugene Hwang, MD

Principal Investigator

Children's National Research Institute

Brian Rood, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for children under 5 with certain brain tumors (like medulloblastoma, pineoblastoma) who can have a device called an Ommaya reservoir placed in their brain. They should be able to handle the procedure to collect blood cells and have enough tumor tissue available. Their body must be functioning well overall, with acceptable blood counts and organ function.

Inclusion Criteria

My neurological condition has been stable for 2 weeks, and I agree to a short steroid treatment.

My doctor thinks I can have surgery to place a Rickham reservoir.

My parent or guardian can give consent for me.

Exclusion Criteria

Prior immunotherapy with an investigational agent within the last 28 days prior to procurement

I do not have any infections that aren't responding to treatment.

Patients with known HIV infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Standard of Care Treatment

Patients receive up to 3 induction chemotherapy cycles and up to 3 consolidation cycles with autologous stem cell rescue

12-18 weeks

TSA-T Infusion and Monitoring

Patients receive TSA-T infusions with safety monitoring for dose-limiting toxicities

42 days

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term Follow-up

Overall survival and progression-free survival are monitored

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T)

Trial Overview The IMPACT study tests personalized immune cells (TSA-T) designed to target specific proteins on a child's own brain tumor. It's after standard treatments like chemo. The goal is to see if these custom-made cells are safe and how they affect the tumor and the child's immune system.

How Is the Trial Designed?

Group I: Embryonal brain tumors Experimental Treatment 1 Intervention

These patients are young children (\<5 years of age) with newly diagnosed high-risk embryonal CNS malignancies and are expected to have a modest male predominance reflecting the sex-based incidence of pediatric brain tumors. Patients will have a Lansky performance status of ≥60.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Published Research Related to This Trial

CAR-T cell therapy, while currently approved only for B cell malignancies, shows promising potential for treating pediatric brain tumors, with early clinical trials indicating some positive responses.

Recent preclinical studies have identified new tumor antigens and combination strategies that enhance the effectiveness of CAR-T cells, particularly when administered directly to the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells for pediatric brain tumors: Present and future. Leruste, A., Beccaria, K., Doz, F.[2021]

In a first-in-human trial involving 10 heavily pre-treated patients with relapsed or metastatic breast cancer, multi-antigen-targeted T cells (multiTAA-T) were well tolerated with no treatment-related toxicities, indicating a promising safety profile for this therapy.

One patient experienced prolonged disease stabilization for 5 months, which was linked to the in vivo expansion and persistence of T cells targeting specific tumor antigens, along with evidence of broader immune activation against non-targeted tumor antigens in 7 out of 10 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. Hoyos, V., Vasileiou, S., Kuvalekar, M., et al.[2022]

Adoptive transfer of ex vivo activated T lymphocytes from tumor-draining lymph nodes has shown effectiveness in treating experimental brain tumors, requiring both CD4 and CD8 T cells for optimal tumor regression.

A phase I clinical trial is underway to evaluate this T cell therapy for malignant astrocytomas, highlighting its potential as a targeted immunotherapy for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy of intracranial tumors by systemic transfer of tumor-draining lymph node cells (Review). Plautz, G., Shu, S.[2019]

Adoptive T-cell therapy involves using tumor-fighting T-cells that are either taken from the patient or donors, modified in the lab, and then reintroduced into the patient to target and eliminate cancer cells.

Over the past 30 years, various strategies have evolved in adoptive T-cell therapy, leading to more precise targeting of tumors and improved effectiveness in treating cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances in application of adoptive T-cell therapy for cancer patients]. Jixia, Z., Chengyan, Z., Pingli, W.[2023]

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

In a study involving 10 patients with progressive malignant glioma, systemic adoptive immunotherapy was found to be feasible and safe, with no severe toxicities reported, indicating a promising safety profile for this treatment approach.

Two patients experienced significant tumor regression lasting at least 6 months, and one patient maintained stable disease for over 17 months, suggesting potential therapeutic benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic T cell adoptive immunotherapy of malignant gliomas. Plautz, GE., Barnett, GH., Miller, DW., et al.[2007]

Cytotoxic T lymphocytes (CTLs) play a crucial role in fighting cancer by recognizing tumor-specific antigens, which are presented by cells in the body.

The review discusses the development of peptide-based vaccines that target these tumor-associated antigens, highlighting their potential to enhance the immune response against cancer and improve CTL therapy in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy - review]. Liu, Y.[2016]

Adoptive cell therapies, particularly chimeric antigen receptor (CAR) T-cell therapies, are showing promise in treating aggressive primary brain tumors like glioblastoma and diffuse midline glioma, H3 K27M-mutant, which have been challenging to treat with traditional immunotherapy.

Despite the potential of CAR T-cell therapies, significant challenges remain in their development and implementation for brain tumor patients, indicating that while progress is being made, more work is needed to achieve transformative benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapies for the Treatment of Primary Brain Tumors. Mount, CW., Gonzalez Castro, LN.[2022]

Adoptive T cell transfer (ACT) using CAR-T cells shows great promise in treating hematological cancers, as these engineered T cells can specifically target cancer cells, but they also pose risks of severe side effects like cytokine release syndrome and neurotoxicity.

Challenges remain in applying CAR-T therapy to solid tumors due to their complex antigens and microenvironments, leading to ongoing clinical trials aimed at enhancing the safety and effectiveness of CAR-T cells in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cell and Personalized Medicine. Cruz-Ramos, M., García-Foncillas, J.[2020]

Adoptive cell therapy using CAR T cells has shown great success in treating B-cell malignancies, leading to FDA approval, but has faced challenges in effectively targeting pediatric solid tumors and brain tumors due to factors like varied antigen expression and a hostile tumor environment.

The review discusses ongoing strategies to improve the effectiveness of CAR T-cell therapy for solid tumors, highlighting the need to enhance T cell migration to tumor sites and overcome the immunosuppressive conditions present in these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors. DeRenzo, C., Krenciute, G., Gottschalk, S.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06193759

NCT06193759 | Immunotherapy for Malignant Pediatric ... This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10326126/

Cellular Therapy for Children with Central Nervous System ... Patient outcomes for malignant CNS tumors remain poor, so - after decades exhausting the benefit of resection, radiation, chemotherapy, and ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-brain-1-2024-70fd3

Adoptive Cellular Therapy for Pediatric Brain Tumors What data supports the effectiveness of the treatment Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) for pediatric brain tumors? Research shows ...

4. braintumor.org braintumor.org/news/new-brain-tumor-clinical-trials-april-october-2024/

New Brain Tumor Clinical Trials: April – October 2024 This report provides a summary of the studies that have recently opened or started recruiting since our last report for patients with a primary brain tumor.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/448517

Immunotherapy for Malignant Pediatric Brain Tumors ... This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT06193759

Immunotherapy for Malignant Pediatric Brain Tumors ... This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against ...