Cancer Vaccine + Nivolumab for Brain Tumor

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Sabine Mueller, MD, PhD

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This is 3-arm, multicenter study that will be conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC). This study will assess the safety and immune activity of a synthetic peptide vaccine specific for the Histone 3 lysine27-to-methionine (H3.3K27M) epitope given in combination with poly-ICLC and the H3.3K27M epitope given in combination with poly-ICLC and the PD-1 inhibitor, nivolumab, in HLA-A2 (02:01)+ children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or other midline gliomas that are positive for H3.3K27M.

Eligibility Criteria

This trial is for children aged 3-21 with newly diagnosed DIPG or other gliomas positive for H3.3K27M mutation, who've had standard radiation therapy but no prior chemo, immunotherapy, or bone marrow transplant. They must have good organ function and agree to use contraception if applicable. Those on stable steroids can join; however, those with certain health conditions or treatments are excluded.

Inclusion Criteria

I am a child aged 3-21 with a specific brain tumor mutation and have had standard radiation.

I am a child aged 3-21 with a specific brain tumor type and have completed standard radiation therapy.

I am a child (3-21) with a specific brain tumor (not DIPG) and have had standard radiation.

+8 more

Exclusion Criteria

I do not have any infections that are not responding to treatment.

I have had a solid organ or bone marrow transplant.

Patients currently receiving or previously treated with investigational drugs

+6 more

Participant Groups

The study tests a synthetic peptide vaccine targeting the H3.3.K27M epitope combined with poly-ICLC and nivolumab (a PD-1 inhibitor) in children who express a specific genetic marker (HLA-A*02:01). It aims to evaluate safety and immune response across three groups within this patient population.

3Treatment groups

Experimental Treatment

Group I: Stratum C: Newly Diagnosed DIPG or other Midline GliomaExperimental Treatment2 Interventions

Newly diagnosed children with DIPG or other midline gliomas (excluding primary spinal cord tumors) who are positive for HLA-A2 (02:01) and the H3.3K27M mutation that underwent radiation therapy will receive the specific H3.3K27M peptide vaccine, combined with the tetanus toxoid peptide, emulsified in Montanide. Poly-ICLC, which is a synthetic nucleic acid, will be given concurrently to improve the therapeutic effects of the vaccine. Nivolumab will also be given via IV. Vaccine will be given every 3 weeks for the first 24 weeks, then if there is stable or improved disease, will be given every 6 weeks for a total treatment period of 96 weeks. Nivolumab will continue to be given every 3 weeks throughout all of treatment.

Group II: Stratum B: Newly Diagnosed Glioma (non-DIPG)Experimental Treatment1 Intervention

Newly diagnosed children with gliomas other than DIPG who are positive for HLA-A2 and the H3.3K27M mutation that underwent radiation therapy will receive the specific H3.3K27M peptide vaccine, combined with the tetanus toxoid peptide, emulsified in Montanide. Poly-ICLC, which is a synthetic nucleic acid, will be given concurrently to improve the therapeutic effects of the vaccine. Vaccine will be given every 3 weeks for the first 24 weeks, then if there is stable or improved disease, will be given every 6 weeks for a total treatment period of 96 weeks.

Group III: Stratum A: Newly Diagnosed DIPGExperimental Treatment1 Intervention

Newly diagnosed children with diffuse intrinsic pontine glioma who are positive for HLA-A2 and the H3.3K27M mutation that underwent radiation therapy will receive the specific H3.3K27M peptide vaccine, combined with the tetanus toxoid (TT) peptide, emulsified in Montanide. Poly-ICLC, which is a synthetic nucleic acid, will be given concurrently to improve the therapeutic effects of the vaccine. Vaccine will be given every 3 weeks for the first 24 weeks, then if there is stable or improved disease, will be given every 6 weeks for a total treatment period of 96 weeks.