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.
Participants who are eligible will receive a specific peptide vaccine, along with a helper drug called poly-ICLC, in combination with nivolumab, every 3 weeks for the first 6 months of treatment. Participants will be monitored routinely by laboratory assessments, physical evaluation, vital signs, and MRI. Participants who tolerate therapy well and have stable or improved disease after 6 months of treatment can continue to receive treatment, nivolumab continuing every 3 weeks but vaccine and poly-ICLC now every 6 weeks, for a total of 96 weeks of treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
K27M peptide vaccine, combined with Tetanus Toxoid peptide, emulsified in montanide. Poly-ICLC will be given concurrently
anti-programmed cell death protein 1 (PD-1) monoclonal antibody
Rady Children's Hospital-San Diego
San Diego, California, United States
University of California, San Francisco
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, United States
St. Louis Children's Hospital
St Louis, Missouri, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
...and 5 more locations
Percentage of Participants With Adverse Events (AE) Related to Treatment
Safety of the vaccine (Strata A and B) or vaccine in combination with nivolumab (Stratum C) will be assessed for participants who received the vaccination. The severity of toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)version 5.0. and include any clinically-significant lab abnormalities meeting Grade 3, 4, or 5 criteria according to CTCAE. Grade 1 \& 2 AEs will be summarized if probably, possible, or definitely related to study therapy. Descriptive statistics will be utilized to display the data on toxicity reported by participants.
Time frame: 24 months
Overall Survival Rate at 12 Months (OS12) (Stratum A Only)
OS12 is defined as the percentage of participants still alive at 12 months, and is the clinical efficacy, primary endpoint for Stratum A. Any eligible participant that received at least one dose of the K27M/TT vaccine will be considered evaluable for clinical efficacy. OS12 will be censored at the last contact date and estimated using the Kaplan-Meier method.
Time frame: 12 months
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