CAR T Cell Therapy for Ependymoma

Not currently recruiting at 13 trial locations

Overseen By Nina Butingan, MBS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Pediatric Brain Tumor Consortium

Must not be taking: Corticosteroids, Herbal medications

Disqualifiers: HIV, Bulky tumors, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new immune therapy called HER2 CAR T cells to determine its safety and effectiveness in treating ependymoma, a type of brain tumor in children that has returned or isn't responding to treatment. The treatment uses the patient's own blood cells, genetically modified to attack the tumor. It targets tumors with a specific protein called HER2. Children diagnosed with recurrent or progressive ependymoma who have undergone standard treatments like surgery and radiation might be suitable candidates for this study. As a Phase 1 trial, this 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 requires that patients stop taking certain medications before enrollment. Specifically, patients must not have received cytotoxic chemotherapy, biological, targeted, or investigational agents for at least 28 days prior to enrollment. Additionally, patients must stop using herbal medications and dietary supplements at least 7 days before enrollment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that a new type of immune therapy, HER2 CAR T cells, is being tested for safety in treating ependymoma, a type of brain tumor. Early studies suggest that HER2 CAR T cells show promise and have been well tolerated in treatments involving children. These cells, made from a patient's own blood, are designed to find and destroy cancer cells. While the main focus of these studies is to assess the therapy's safety, most patients have not experienced severe side effects. However, since this research is in its early stages, side effects might still occur and are being closely monitored. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ependymoma, which typically include surgery, radiation, and chemotherapy, HER2 Specific CAR T Cell therapy offers a novel approach. This treatment is unique because it harnesses the power of the immune system by engineering patients' T cells to specifically target and attack tumor cells expressing the HER2 protein. Researchers are excited about this therapy because it represents a precision approach, potentially offering greater effectiveness with fewer side effects compared to traditional methods. Additionally, this therapy could provide new options for patients whose tumors are resistant to conventional treatments.

What evidence suggests that HER2 CAR T cells might be an effective treatment for ependymoma?

Research has shown that HER2 CAR T cells might be effective against ependymoma tumors with the HER2 protein. These specialized cells are designed to locate and attack this protein on the tumor, potentially shrinking or eliminating it. In this trial, participants will receive HER2 CAR T cells in two different treatment arms. Early results suggest that adding anti-PD-1 antibodies can enhance the effectiveness of these CAR T cells against HER2-positive tumors. Studies also indicate that targeting HER2 holds promise for treating ependymoma. While further research is necessary, these findings offer hope that HER2 CAR T cells could serve as a valuable treatment for this challenging condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Meenakshi Hegde, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for children aged 1 to 21 with recurrent or progressive ependymoma, a type of brain tumor. They must have had standard treatments and be HER2-positive. Kids need to be in good enough health with stable neurological conditions and not on other cancer treatments.

Inclusion Criteria

Patient or parent/guardian must be able to understand and sign a written informed consent document

My organs and bone marrow are functioning well.

I've had surgery and radiation for my condition as standard treatment.

Exclusion Criteria

I have had a condition where lymphocytes are produced in excessive amounts.

Patient is living outside the US

Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Chemotherapy

Patients receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine prior to CAR T cell infusion

1 week

Daily visits for chemotherapy administration

Treatment

Patients receive HER2 CAR T cells infusion. Treatment repeats every 8 to 12 weeks for up to 3 cycles

9 months

1 visit per infusion cycle

Surgical Study

Patients undergo surgical tumor resection 4-6 weeks after CAR T cell infusion, followed by additional CAR T cell infusions

10 months

1 surgical visit, followed by infusion visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• HER2 Specific CAR T Cell

Trial Overview The study tests HER2 CAR T cells, which are the patient's own immune cells genetically modified to attack their tumor by recognizing a protein called HER2. It aims to see how safe this treatment is and how well it works against ependymoma in kids.

How Is the Trial Designed?

Group I: Treatment (HER2 CAR T cells), Surgical Arm Experimental Treatment 1 Intervention

Patients receive lymphodepletion chemotherapy with cyclophosphamide IV daily on Days -7 to -6 and fludarabine IV daily on Days -5 to -1. Patients receive HER2 CAR T cells IV on Day 0 followed by surgical tumor resection 4-6 weeks following HER2 CAR T cell infusion. Treatment repeats every 8 to 15 weeks for 2 additional cycles in the absence of disease progression or unacceptable toxicity.

Group II: Treatment (HER2 CAR T cells), Phase I Arm Experimental Treatment 1 Intervention

Patients receive lymphodepletion chemotherapy with cyclophosphamide IV daily on Days -7 to -6 and fludarabine IV daily on Days -5 to -1. Patients receive HER2 CAR T cells IV on Day 0. Treatment repeats every 8 to 12 weeks for 2 additional cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Pediatric Brain Tumor Consortium

Lead Sponsor

Trials

38

Recruited

1,600+

American Lebanese Syrian Associated Charities (ALSAC)

Collaborator

Trials

9

Recruited

670+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

American Lebanese Syrian Associated Charities

Collaborator

Trials

9

Recruited

670+

Texas Children's Cancer Center

Collaborator

Trials

8

Recruited

220+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

Chimeric antigen receptor T cells targeting EPHA2, HER2, and interleukin 13 receptor α2 have been validated as effective treatments for recurrent medulloblastoma and ependymoma in mouse models, showing promise for bypassing the blood-brain barrier through intrathecal delivery.

The combination of these targeted T cells with azacytidine demonstrated high efficacy against multiple metastatic models of group 3 medulloblastoma and PFA ependymoma, suggesting a strong rationale for future clinical trials in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma. Donovan, LK., Delaidelli, A., Joseph, SK., et al.[2022]

HER2-BBz-CAR T cells demonstrated strong anti-tumor efficacy against pediatric medulloblastoma in preclinical models, effectively clearing tumors in mice through both regional and intravenous delivery methods.

In non-human primates, intraventricular delivery of HER2-BBz-CAR T cells was well-tolerated without systemic toxicity, suggesting a safe approach for future clinical trials in children with relapsed medulloblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. Nellan, A., Rota, C., Majzner, R., et al.[2020]

Optimizing the design of HER2-CAR T cells, particularly using the 4-1BB costimulatory domain, enhances their ability to target tumors and reduces T-cell exhaustion, making them more effective against breast cancer metastases in the brain.

Local and regional delivery methods, especially intraventricular administration, demonstrated significant antitumor activity in mouse models with multifocal brain metastases, suggesting a promising approach for treating this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain. Priceman, SJ., Tilakawardane, D., Jeang, B., et al.[2020]

Patients with supratentorial extraventricular ependymoma (SEE) who underwent gross total resection (GTR) had significantly better progression-free survival compared to those who had subtotal resection (STR), with STR patients facing much higher recurrence risks over time.

The expression of PD-L1 was identified as an independent predictor of worse outcomes in SEE patients, suggesting that PD-L1 positivity correlates with increased recurrence rates and could serve as a reliable biological marker for prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of clinical factors and immunocheckpoint molecules in the prognosis of patients with supratentorial extraventricular ependymoma: a single-center retrospective study. Wang, L., Han, S., Yan, C., et al.[2021]

CNS tumors are a major challenge in pediatric cancer, accounting for 25% of diagnoses and being the leading cause of cancer-related deaths in children, highlighting the urgent need for improved treatments.

CAR T cell therapy has shown promise in treating B-cell malignancies, but its effectiveness against pediatric CNS tumors is limited due to factors like tumor location, varied antigen expression, and the protective blood-brain barrier, necessitating innovative strategies to enhance its success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours. Ferreras, C., Fernández, L., Clares-Villa, L., et al.[2022]

Intracranial delivery of HER2-targeting CAR-T cells was found to be well tolerated in a small group of 3 patients with central nervous system (CNS) tumors, indicating a potential safe application for this therapy.

This study suggests that targeting HER2 with CAR-T cells could be a promising approach for treating CNS tumors, although further research with larger patient groups is needed to confirm efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregional Delivery of CAR-T Cells Is Feasible in Pediatric CNS Tumors. [2022]

HER2-specific T cells can effectively recognize and kill HER2-positive medulloblastoma cells, showing significant T-cell activation and proliferation in response to these tumors.

In vivo studies demonstrated that transferring HER2-specific T cells led to sustained regression of established medulloblastomas, suggesting that this approach could be a promising immunotherapy for treating this type of brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of experimental medulloblastoma following transfer of HER2-specific T cells. Ahmed, N., Ratnayake, M., Savoldo, B., et al.[2014]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04903080

NCT04903080 | HER2-specific Chimeric Antigen Receptor ... These HER2-specific CAR T cells may be able to target and kill ependymoma tumors that express HER2. This research is also studying how doable it is to provide ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12133747/

Research progress on HER2-specific chimeric antigen ... The results demonstrated that anti-PD-1 antibodies can significantly enhance the efficacy of anti-HER2 CAR-T cells against HER2-positive solid ...

3. nationwidechildrens.org nationwidechildrens.org/research/clinical-research/cell-therapy/nct04903080

Clinical Study for Children with Hard-to-Treat or Returning ... The purpose of this study is to evaluate the safety profile of a type of immune therapy called HER2 CAR T cells (short for HER2 chimeric antigen receptor T ...

4. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii236/7890284

EXTH-03. CAR T-CELLS TARGETED TO B7-H3 OR HER2 ... Our work shows that both B7-H3 and HER2 are good targets against EPN, despite drastic differences in antigen density. Results suggest that lower ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-06710

Testing the Safety and Feasibility of HER2 CAR T Cells in ... This phase I trial assesses the side effects of HER2-chimeric antigen receptor (CAR) T-cells in treating patients with ependymoma that has come back ...

6. academic.oup.com academic.oup.com/noa/article/5/1/vdad024/7151530

HER2 chimeric antigen receptor T cell immunotherapy is an ... HER2 CAR T cells are already in clinic development and are well tolerated in pediatric patients. Here we provide strong preclinical evidence for ...