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

Trial Summary

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.

What data supports the effectiveness of the treatment HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC for brain tumors?

Research shows that peptide vaccines like IMA950, which include components similar to HLA-A2 Restricted Glioma Antigen-Peptides, can trigger immune responses that target brain tumors. Studies have demonstrated that these vaccines, when combined with Poly-ICLC, can enhance the body's ability to fight gliomas by promoting specific T-cell responses, which are crucial for attacking tumor cells. ^{1 2 3 4 5}

Is the vaccine for brain tumors safe for humans?

The vaccine, which includes HLA-A2 restricted glioma antigen-peptides with poly-ICLC, has been tested in early phase clinical trials and is generally well tolerated in humans, with no significant safety concerns reported. ^{1 2 3 5 6}

What makes the HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC treatment unique for brain tumors?

This treatment is unique because it uses a vaccine approach to stimulate the body's immune system to target and kill brain tumor cells by using specific peptides (small proteins) that are associated with glioma, combined with poly-ICLC, which enhances the immune response. Unlike traditional treatments, this method aims to train the immune system to recognize and attack tumor cells, potentially offering a new way to treat brain tumors that are resistant to standard therapies. ^{1 2 3 7 8}

What is the purpose of this trial?

The study will assess the immunogenicity, safety and preliminary clinical efficacy of the glioma associated antigen (GAA)/tetanus toxoid (TT) peptide vaccine and poly-ICLC in HLA-A2+ children with unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. Radiation therapy counts as one biologic regimen, but patients may not have received radiation to the index lesion within 1 year of enrollment.

Research Team

James Felker, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

References

1. England 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. [2020]

2. United States 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Natural HLA class I ligands from glioblastoma: extending the options for immunotherapy. [2021]

6. United States 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. [2021]

7. United States 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Profound tumor-specific Th2 bias in patients with malignant glioma. [2022]