Clinical Trial: H3.3K27M Peptide Vaccine for Children With Newly Diagnosed DIPG and Other Gliomas

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: H3.3K27M Specific Peptide Vaccine Combined With Poly-ICLC for the Treatment of Newly Diagnosed HLA-A2+ H3.3K27M Positive Diffuse Intrinsic Pontine Glioma (DIPG) as Well as

Brief Summary:

This is a two cohort Phase I study within the Pacific Pediatric Neuro-Oncology Consortium (PNOC).

This study will assess the safety of repeated administration of the H3.3K27M specific vaccine in HLA-A2+ children and young adults with H3.3K27M DIPGs and other gliomas.


Detailed Summary: Subjects who are eligible will receive a specific peptide vaccine, along with a helper drug called poly-ICLC, every 3 weeks for the first 6 months of treatment. Subjects will be monitored routinely by laboratory assessments, physical evaluation, vital signs, and MRI. Subjects who tolerate therapy well and have stable or improved disease after 6 months of treatment can continue to receive treatment, now every 6 weeks, for a total of 96 weeks of treatment.
Sponsor: University of California, San Francisco

Current Primary Outcome:

  • Number of Participants with Adverse Events related to treatment [ Time Frame: 24 months ]
    Safety of the vaccine will be assessed by monitoring for adverse events (AEs), scheduled laboratory assessments, vital signs, & physical examinations for subjects who receive the vaccination. The severity of toxicities will be graded according to the NCI CTCAE v4.0. AEs & clinically significant lab abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity & relationship to study drug(s). Grade 1 & 2 AEs will be summarized if related to study therapy. Descriptive statistics will be utilized to display the data on toxicity seen.
  • Overall survival (OS) at 12 months (OS12) [ Time Frame: 36 months ]
    OS12 will be the clinical efficacy primary endpoint. Any eligible subject that receives at least one dose of the K27M/TT vaccine will be considered evaluable for clinical efficacy. For subjects who are still alive at 12 months, OS12 will be censored at the last contact date. OS will be estimated using the Kaplan-Meier method.


Original Primary Outcome: Same as current

Current Secondary Outcome: Induction of the H3.3K27M epitope-specific cytotoxic T lymphocyte (CTL) response in post vaccine peripheral mononuclear cells (PBMC) in HLA-A2+ children with DIPG and other gliomas [ Time Frame: 36 months ]

A subject will be considered to have responded, if at any of post-vaccine time point against H3.3K27M antigen, the number of spots is double that at baseline, and there are at least 10 spots/20,000 cells, and if the number of the post-vaccine spots is at least three times the standard-deviation of the pre-vaccine value. This definition provides some protection against false positive response. We will correlate response with OS data. We will plot the time course of the magnitude of response and model it using a mixed-effects model approach.


Original Secondary Outcome: Same as current

Information By: University of California, San Francisco

Dates:
Date Received: November 2, 2016
Date Started: November 2016
Date Completion: November 2020
Last Updated: February 10, 2017
Last Verified: February 2017