Multi-antigen T Cell Therapy for Brain Cancer

(REMIND Trial)

Not currently recruiting at 1 trial location

Overseen By Fahmida Hoq, MBBS, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Must not be taking: Immunosuppressive antibodies

Disqualifiers: Uncontrolled infections, HIV, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 42 days for initial monitoring, up to 1 year for additional infusions

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAA-T (Multi-antigen T Cell Therapy), which uses the body’s immune cells to combat brain cancer. The goal is to determine its safety for individuals with hard-to-treat brain cancers, such as DIPG or other aggressive tumors. Suitable participants have brain tumors resistant to standard treatments and have faced these challenges for some time. The trial will explore different doses to identify the most effective one. Those who have recently completed treatments like radiation or chemotherapy and still face cancer issues may find this trial suitable. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but there are specific requirements for stopping certain treatments. You must stop myelosuppressive chemotherapy at least 14 days before the TAA-T infusion, investigational agents 28 days prior, and biologic agents 7 days prior. Bevacizumab can be used if needed without a standard washout period.

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

Research has shown that TAA-T cells, a type of immune cell therapy, effectively and safely treat other solid tumors and breast cancer. In these studies, patients generally handled the treatment well. Some side effects occurred, but they were usually mild, such as fever or tiredness.

This trial is in its early stage, primarily focused on ensuring the treatment's safety for people. As it is in an early phase, researchers are still gathering safety information, but the treatment's success in other cancers offers some reassurance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about TAA-T because it offers a new approach to tackling brain cancer using multi-antigen T cell therapy. Unlike traditional treatments like surgery, radiation, and chemotherapy, which target the tumor directly, TAA-T works by harnessing the body's immune system to attack cancer cells. This treatment infuses patients with specially engineered T cells that recognize and target multiple tumor-associated antigens, potentially improving the precision and effectiveness of the attack on cancer cells. By focusing on the immune system's power, TAA-T could lead to more personalized and potentially less toxic treatments for patients with brain cancer.

What evidence suggests that TAA-T might be an effective treatment for brain cancer?

Research has shown that TAA-T cells, a type of immune therapy using the body's own cells, effectively treat other solid tumors and breast cancer. These cells target specific proteins on cancer cells to destroy them. In early studies, patients receiving TAA-T therapy demonstrated positive responses, such as slowed tumor growth. This trial will evaluate TAA-T for difficult brain cancers like DIPG and other central nervous system (CNS) tumors. Although more research is needed, the targeted approach of TAA-T presents a promising option for these challenging conditions. ^{2 3 6 7 8}

Who Is on the Research Team?

Eugene Hwang, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for pediatric and adult patients aged 6 months to 80 years with high-risk central nervous system (CNS) tumors, including DIPG, glioma, medulloblastoma, and other aggressive malignancies. Participants must have stable neurologic deficits if present, meet organ function requirements like adequate blood counts and liver function tests, not be pregnant or breastfeeding, agree to use contraception if applicable, and have recovered from prior treatments.

Inclusion Criteria

Available pre-trial tumor tissue (Optional for Group B patients, but highly encouraged)

My blood counts and liver/kidney functions are within required ranges.

My neurological symptoms have been stable for at least a week.

Exclusion Criteria

I have a history of cancer.

I have had a condition where my lymphocytes grow abnormally.

I do not have any infections that are currently uncontrolled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy (Group A) / Conventional Therapy (Group B)

Completion of radiotherapy for Group A or conventional therapy for Group B before TAA-T infusion

Varies per patient

Treatment

Participants receive TAA-T infusions with dose escalation and monitoring for adverse events

42 days for initial monitoring, up to 1 year for additional infusions

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• TAA-T

Trial Overview The trial is testing TAA-T cells made from the patient's own blood to fight brain tumors. It has two groups: one for new cases of a specific tumor in the brainstem after radiotherapy (Group A), another for recurrent or hard-to-treat CNS tumors after standard therapy (Group B). The safety and ability to make these personalized immune cells quickly are being studied.

How Is the Trial Designed?

Group I: TAA-T Experimental Treatment 1 Intervention

Three different dosing schedules will be evaluated. Dose Level One: 2 x 107 cells/m2 Dose Level Two: 4 x 107 cells/m2 Dose Level Three: 8 x 107 cells/m2 Group A patients (DIPG): The first TAA-T dose will be infused any time more than or equal to 14 days after completion of radiotherapy. Group B patients (other recurrent/progressive/refractory CNS tumors): TAA-T will be infused any time more than or equal to 14 days after completing most recent course of conventional (non-investigational) therapy for their disease AND after appropriate washout periods as detailed in eligibility criteria. Ideally, patients should not receive other systemic antineoplastic agents for at least 42 days after the infusion of TAA-T, although such treatment may be added if deemed critical for patient care by the attending physician.

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Published Research Related to This Trial

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]

Co-administering tumor-associated antigen (TAA)-specific CD8+ T cells with TH1 polarized CD4+ T cells enhances the recruitment of these effector cells to brain tumors, which is crucial for effective immunotherapy.

Interestingly, while TH1 polarization improves initial recruitment, it is not necessary for the long-term therapeutic success of combined CD4+ and CD8+ T cell transfer, suggesting flexibility in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Getting by with a little help from the right CD4+ T cells. Hoepner, S., Walker, PR.[2021]

MDM2-specific T cells can survive in the body despite being exposed to normal tissue expression, but they struggle to proliferate and function effectively, leading to high rates of cell death when stimulated by their target antigen.

Cytokines like IL-2 and IL-15 can help improve the survival and function of these T cells, but they do not restore their full effectiveness, indicating potential challenges for immunotherapy targeting common tumor-associated antigens like MDM2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of T cell tolerance to the tumor-associated antigen MDM2: cytokines can restore antigen responsiveness, but not high avidity T cell function. Bendle, GM., Xue, SA., Holler, A., 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]

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]

Recombinant monoclonal antibodies (MAbs) are becoming important in cancer therapy, especially when used alongside traditional anti-cancer drugs, enhancing treatment effectiveness.

Combining antibody therapy with toxins or radioisotopes, and developing immune cells like cytotoxic T-lymphocytes (CTLs) or natural killer (NK) cells that target tumor-associated antigens (TAAs), could significantly improve cancer immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible applications of antibodies or their genes in cancer therapy. Kuroki, M., Huang, J., Shibaguchi, H., et al.[2007]

In a study involving 15 patients with recurrent astrocytoma, researchers successfully generated and expanded tumor-specific T cells from patients' blood after immunization with their own tumor cells, demonstrating the feasibility of this approach.

The intravenous transfer of these stimulated T cells was well-tolerated with limited toxicity, paving the way for future controlled studies to evaluate the anti-tumor effects of this immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous tumor cell vaccination combined with adoptive cellular immunotherapy in patients with grade III/IV astrocytoma. Holladay, FP., Heitz-Turner, T., Bayer, WL., et al.[2019]

Human T cells can be genetically modified to express tumor-associated antigens, making them potential candidates for effective antigen-presenting cells in cancer immunotherapy.

The successful induction of tumor-specific T cell immune responses requires the activation of T cells using CD3/CD28 antibodies along with proinflammatory cytokines like IL-7 and IL-12, highlighting the importance of these components in developing cellular cancer vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modification of T lymphocytes to express tumor antigens. Foster, AE., Song, XT.[2021]

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-1-brain-neoplasms-11-2018-29613

Multi-antigen T Cell Therapy for Brain Cancer (REMIND Trial) Research shows that TAA-T cells, which are a type of immune cell therapy, have been effective and safe in treating other types of solid tumors and breast cancer ...

2. trial.medpath.com trial.medpath.com/clinical-trial/ae7f3c3aa18f99bc/phase-1-t-cell-infusion-neuro-oncologic-disease

Multi-antigen T Cell Infusion Against Neuro-oncologic Disease This Phase I dose-escalation trial is designed to determine the safety and feasibility of rapidly generated tumor multi-antigen associated specific ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9290161/

Multi-antigen-targeted T-cell therapy to treat patients with ... In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1476558623000349

Translational considerations for immunotherapy clinical ... We discuss unique immunotherapy clinical trial challenges, including toxicity considerations, disease assessment, and correlative studies.

5. link.springer.com link.springer.com/article/10.1007/s11912-023-01423-3

Cellular Therapy for Children with Central Nervous System ... Here, we review the correlative science in adoptive cell therapy (ACT) for childhood central nervous system (CNS) tumors.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03652545/

Clinical Trial: NCT03652545 This Phase I dose-escalation trial is designed to determine the safety and feasibility of rapidly generated tumor multi-antigen associated ...

7. smartpatients.com smartpatients.com/trials/NCT03652545

Multi-antigen T Cell Infusion Against Neuro-oncologic ... This Phase I dose-escalation trial is designed to determine the safety and feasibility of rapidly generated tumor multi-antigen associated specific ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05238792

NCT05238792 | Multi Tumor-Associated Antigen-Specific T ... The TAA-T product will be assessed for safety and anti-tumor activity. Intervention/Treatment, Biological : Tumor-associated antigen-specific T cell (TAA-T).