PNOC007: H3.3K27M Peptide Vaccine for Children with Newly Diagnosed DIPG and Other Gliomas

H3.3K27M Specific Peptide Vaccine with Poly-ICLC for HLA-A2+ H3.3K27M Positive Diffuse Intrinsic Pontine Glioma (DIPG) and Other Gliomas

Category:

Brain Tumor

Diseases Treated:

DIPG, glioma

Eligibility Overview:

  • Newly diagnosed diffuse intrinsic pontine glioma (DIPG) or other glioma
  • At least 3 years old and 21 or younger
  • Positive for HLA-A2
  • Has undergone tumor biopsy
  • Positive H3.3 K27M mutation in tumor
  • Has received standard radiation therapy
  • No prior chemotherapy, immunotherapy or bone marrow transplant
  1. Brief Summary

    There are no currently available, effective treatments for pediatric malignant gliomas. Outcomes are especially poor for patients with gliomas located within midline structures, such as diffuse intrinsic pontine glioma (DIPG).

    Malignant gliomas in children often show recurrent missense mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3. Prior research suggests a specific peptide that includes the K27M mutation can induce specific, HLA-A2-dependent cytotoxic T lymphocyte (CTL) responses. Induced CTLs recognize the H3.3 K27M epitope endogenously expressed in glioma cell lines that also harbor the K27M mutation. Therefore, H3.3 K27M represents a novel, shared neo-epitope for T-cell-dependent vaccine immunotherapy in patients with this type of brain tumor.

    This clinical trial tests the safety and immunological response of a vaccine using a specific synthetic peptide for the H3.3 K27M epitope in HLA-A2+ children with newly diagnosed DIPG or other gliomas that are positive for the H3.3 K27M mutation.

    Primary Objective

    • To assess the safety of repeated administration of the H3.3 K27M epitope-specific vaccine in HLA-A2+ children with H3.3 K27Mmutated gliomas, including DIPGs
    • To determine the 12 month overall survival (OS12) in HLA-A2+ children with H3.3 K27M mutated gliomas including DIPG that are being treated with repeated administration of the H3.3 K27M peptide vaccine

    Eligibility Criteria

    Inclusion criteria include:

    • Newly diagnosed DIPG (Stratum A) OR newly diagnosed non-DPIG glioma, including spinal cord glioma
    • At least 3 years old and 21 or younger
    • Positive for HLA-A2
    • Has undergone tumor biopsy
    • Positive H3.3 K27M mutation in tumor
    • Has received standard radiation therapy
    • No prior chemotherapy, immunotherapy or bone marrow transplant

    Exclusion Criteria include:

    • Current or prior use of investigational drugs
    • Current or prior treatment with other anti-cancer agents
    • Known immune disorder
    • Pregnant or breastfeeding

    Study Sites

    St. Jude Children's Research Hospital
    Memphis, Tennesse

    Collaborating sites in the U.S.

  2. About this study

    This clinical trial will test the safety of a new treatment for children and young adults with brain tumors known as DIPGs. Patients with some other types of glioma may also be eligible to participate.

    The new treatment uses a vaccine to educate the immune system to attack brain tumor cells that have a mutation, or change, in a specific gene. Doctors will give the vaccine along with a drug to help boost the body’s immune system activity. This combination is considered experimental, because it is not approved by the U.S. Food and Drug Administration (FDA).

    Purpose of this clinical trial

    The main goal of this study is to learn the good and bad effects the treatment has on children and young adults with a particular type of brain tumor.

    Eligibility overview

    • Newly diagnosed DIPG or other glioma
    • At least 3 years old and 21 or younger
    • Positive for HLA-A2
    • Has undergone tumor biopsy
    • Positive H3.3K27M mutation in tumor
    • Has received standard radiation therapy
    • No prior chemotherapy, immunotherapy or bone marrow transplant
  3. PNOC007 Quick View
    Sponsors University of California at San Francisco and Pacific Pediatric Neuro-Oncology Consortium
    ClinicalTrials.Gov identifier NCT02960230
    Trial Start Date November 2016
    Estimated Enrollment 29 (5 at St. Jude)
    Study Type Interventional
    Study Phase Phase I
    Conditions DIPG, glioma
    Ages 3 to 21 years old
    Principal Investigator Kellie Haworth, MD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in the U.S.
    For a consultation or to discuss PNOC007 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 901-595-2544 or 901-595-4599
Fax: 901-595-6211

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: (901) 595-2544
FAX: (901) 595-6211

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.