Vaccine for Brain Tumor

Overseen By James Felker, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: James Felker

Must not be taking: Interferon, Interleukins, Immunosuppressives, others

Disqualifiers: Autoimmune disorders, HIV, 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: 11

Duration: 24 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to help the immune system combat low-grade brain tumors in children. The treatment combines special proteins from brain tumors with Poly-ICLC to enhance the immune response. Researchers aim to determine if this vaccine is safe and if it slows tumor growth. Children with hard-to-remove brain tumors who have already tried at least two cancer treatments might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering hope for new, effective options.

Will I have to stop taking my current medications?

You may need to stop certain medications before joining the trial. Specifically, you must be off medications like interferon, allergy shots, growth factors, interleukins, and any investigational drugs for at least one week before starting. If you're on immunosuppressive drugs, you need to stop them four weeks before the trial.

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

Research has shown that the vaccine treatment using specific proteins with Poly-ICLC is generally well-tolerated in patients. In studies with children who have recurring low-grade brain tumors, this vaccine showed early signs of safety and triggered an immune response. While some side effects may occur, they are usually manageable. Researchers continue to study this treatment carefully to ensure safety, but early results are promising for prospective trial participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often include surgery, radiation, and chemotherapy, this new vaccine approach uses HLA-A2 restricted glioma antigen-peptides combined with Poly-ICLC to stimulate the immune system. Researchers are excited because this vaccine targets specific antigens found in glioma cells, potentially allowing the immune system to recognize and attack the tumor more effectively. Additionally, the use of Poly-ICLC as an adjuvant helps to boost the body's immune response to the vaccine, which could lead to better outcomes with fewer side effects than traditional therapies. This innovative approach represents a shift towards more personalized and targeted cancer treatments.

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

Research has shown that the HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC vaccine, administered to all trial participants, can activate the immune system in children with recurring low-grade brain tumors. Studies have found that this vaccine is generally well tolerated, typically not causing major side effects. Early results suggest that the vaccine may help fight the tumor. The combination of glioma antigen peptides and Poly-ICLC aims to help the immune system identify and attack tumor cells. Initial evidence supports this approach, indicating potential benefits for patients. ^{1 2 3 4 6}

Who Is on the Research Team?

James Felker, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for children and young adults aged between 1 to less than 22 years with low-grade gliomas that have undergone at least two prior treatments, including chemotherapy or radiation. Participants must be HLA-A2 positive, stable on low-dose steroids or off steroids for a week, not pregnant, free of infections requiring IV antibiotics for seven days, and have good organ function.

Inclusion Criteria

My low-grade glioma is inoperable, treated with at least two therapies, and hasn't been radiated in the last year.

My immune system marker, HLA-A2, is positive.

I am between 12 months and 22 years old.

Exclusion Criteria

I have not taken any interferons, allergy shots, growth factors, interleukins, or experimental drugs in the last week.

I haven't used strong immune system suppressing drugs in the last 4 weeks.

Patients living outside of North America are not eligible.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous injections of GAA/TT-vaccines and i.m. poly-ICLC every 3 weeks for up to 8 cycles

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up MRIs

24 weeks

3 visits (in-person)

Extension

Participants eligible for additional vaccinations every 6 weeks for up to two years if tumor shrinkage or stable disease is observed

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC

Trial Overview The trial tests the safety and effectiveness of a vaccine combining glioma antigen peptides with an immune booster called Poly-ICLC in patients who are genetically compatible (HLA-A2+). It aims to see if this can stimulate the immune system against brain tumors without surgery.

How Is the Trial Designed?

Group I: HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC Experimental Treatment 1 Intervention

All subjects will receive vaccine plus Poly-ICLC. Injections will be given every 3 week for a total of 8 vaccines.

Who Is Running the Clinical Trial?

James Felker

Lead Sponsor

Trials

3

Recruited

110+

Ian F. Pollack, M.D.

Lead Sponsor

Trials

5

Recruited

130+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Connor's Cure

Collaborator

Trials

2

Recruited

90+

Published Research Related to This Trial

This study is the first to analyze HLA-peptide presentation patterns in HLA-A 02 negative glioma tissues, identifying numerous candidate peptides for immunotherapy derived from proteins important in glioma biology.

The findings allow for the development of personalized immunotherapeutic strategies tailored to HLA-A 02 negative patients, potentially improving treatment options for this challenging type of brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural HLA class I ligands from glioblastoma: extending the options for immunotherapy. Neidert, MC., Schoor, O., Trautwein, C., et al.[2021]

A study identified five novel immunogenic tumor-associated antigens (TAAs) in IDHmut gliomas, which were recognized by T-cells in up to 56% of unrelated patients, suggesting potential targets for immunotherapy.

These TAAs were predominantly expressed in IDHmut gliomas and glioma stem-like cells, while being nearly absent in normal brain tissues, indicating their specificity and potential safety for targeted treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma. Dettling, S., Stamova, S., Warta, R., et al.[2019]

A pilot trial involving 12 children with recurrent high-grade gliomas showed that peptide vaccinations targeting glioma-associated antigens were generally well tolerated, with no significant non-CNS toxicity reported.

The treatment demonstrated preliminary immunological responses in 9 out of 10 children tested, with one child experiencing a partial response lasting over 2 years, suggesting potential clinical activity despite the overall poor prognosis of these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. Pollack, IF., Jakacki, RI., Butterfield, LH., et al.[2021]

The study identified novel HLA Class-II restricted peptides from glioma-associated antigens that can effectively stimulate CD4+ helper T cell responses in patients with malignant gliomas, indicating potential for immunotherapy.

Patients with glioblastoma, especially those with recurrent tumors, showed a significant reduction in the IFN-γ/IL-5 ratio, suggesting a shift towards a Th2 immune response; thus, therapeutic strategies should aim to enhance the Th1 response for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profound tumor-specific Th2 bias in patients with malignant glioma. Shimato, S., Maier, LM., Maier, R., et al.[2022]

A study of 159 patients with grade II/III gliomas revealed significant over-expression of specific tumor-associated antigens (BCAN, CSPG4, IGF2BP3, PTPRZ1, and TNC) at both mRNA and protein levels, indicating their potential as targets for immunotherapy.

In a smaller group of 27 patients, spontaneous T cell responses to the IMA950 antigens were detected in all grade II patients and 71% of grade III patients, suggesting that these antigens are relevant for effective tumor targeting and could enhance the efficacy of immunotherapy when combined with other peptides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma. Dutoit, V., Migliorini, D., Ranzanici, G., et al.[2021]

The phase I/II trial involving 22 patients with recurrent malignant gliomas demonstrated that the α-type 1 polarized dendritic cell (αDC1) vaccine combined with poly-ICLC was well-tolerated and induced immune responses in 58% of patients against glioma-associated antigens.

The treatment showed promising clinical activity, with 9 patients achieving progression-free status for at least 12 months, and one patient experiencing a sustained complete response, indicating potential efficacy in managing recurrent gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. Okada, H., Kalinski, P., Ueda, R., et al.[2023]

Cytotoxic T lymphocytes (CTLs) with a type 1 phenotype (Tc1) are crucial for effectively targeting central nervous system (CNS) tumors, as their homing ability is enhanced by the chemokine CXCL10 and the integrin receptor VLA-4.

A combination of subcutaneous vaccination with glioma-associated antigens and the administration of poly-ICLC significantly increased the presence of Tc1 cells in CNS tumors and improved survival in tumor-bearing mice, leading to a phase I/II clinical trial for patients with recurrent malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tumor immunotherapy with type-1 polarizing strategies. Okada, H.[2020]

The IMA950 multipeptide vaccine, combined with the adjuvant poly-ICLC, was found to be safe and well tolerated in a study involving 19 glioma patients, with only four cases of temporary cerebral edema.

The vaccine successfully elicited CD8 T-cell responses in 63.2% of patients, with median overall survival for glioblastoma patients reaching 19 months, indicating promising immunogenicity and potential effectiveness in treating glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Migliorini, D., Dutoit, V., Allard, M., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4933485/

Immune responses and outcome after vaccination with glioma ... GAA peptide vaccination in children with recurrent LGGs is generally well tolerated, with preliminary evidence of immunological and clinical activity. Keywords: ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT02358187/a-vaccine-trial-for-low-grade-gliomas

A Vaccine Trial for Low Grade Gliomas The study will assess the immunogenicity, safety and preliminary clinical efficacy of the glioma associated antigen (GAA)/tetanus toxoid ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00795457

Effects of Vaccinations With HLA-A2-Restricted Glioma ... The purpose of this study is test the safety and efficacy of an experimental tumor vaccine made from peptides and Montanide ISA-51 in combination with the study ...

4. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02358187/

Clinical Trial: NCT02358187 - Glioma The study will assess the immunogenicity, safety and preliminary clinical efficacy of the glioma associated antigen (GAA)/tetanus toxoid (TT) ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2016-00993

HLA-A2-Restricted Synthetic Glioma Antigen Peptides ... Giving HLA-A2-restricted synthetic glioma antigen peptides vaccine with poly ICLC may kill more tumor cells. Eligibility Criteria ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4297523/

Induction of robust type-1 CD8+ T-cell responses in WHO ... We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) ...