H3.3K27M Peptide Vaccine With Nivolumab for Children With Newly Diagnosed DIPG and Other Gliomas

NCT02960230 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: PNOC 007150819NCI-2017-01830CA209-8TX
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 15

Brief Summary

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.

Conditions

Diffuse Intrinsic Pontine Glioma; Glioma; Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

peptide vaccine; immunotherapy; DIPG; vaccine; nivolumab

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Study Arms (3)

Stratum A: Newly Diagnosed DIPG

EXPERIMENTAL

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.

Biological: K27M peptide

Stratum B: Newly Diagnosed Glioma (non-DIPG)

EXPERIMENTAL

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.

Biological: K27M peptide

Stratum C: Newly Diagnosed DIPG or other Midline Glioma

EXPERIMENTAL

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.

Biological: K27M peptide; Drug: Nivolumab

Interventions

K27M peptide BIOLOGICAL

K27M peptide vaccine, combined with Tetanus Toxoid peptide, emulsified in montanide. Poly-ICLC will be given concurrently

Stratum A: Newly Diagnosed DIPG; Stratum B: Newly Diagnosed Glioma (non-DIPG); Stratum C: Newly Diagnosed DIPG or other Midline Glioma

Nivolumab DRUG

anti-programmed cell death protein 1 (PD-1) monoclonal antibody

Also known as: Keytruda

Stratum C: Newly Diagnosed DIPG or other Midline Glioma

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Stratum A:
• Newly diagnosed children (3-21 years old) with DIPG who are positive for the H3.3K27M mutation (positive testing in Clinical Laboratory Improvement Amendments (CLIA) laboratory) that underwent standard radiation therapy.
• Stratum B:
• Newly diagnosed children (3-21 years old) with diagnosis of glioma other than DIPG who are positive for the H3.3K27M mutation (positive testing in CLIA laboratory) including spinal cord gliomas that underwent standard radiation therapy.
• Stratum C:
• Newly diagnosed children 3-21 years of age with diagnosis of DIPG or midline glioma other than DIPG (excluding primary spinal cord gliomas) who are positive for the H3.3K27M mutation (positive testing from a CLIA or equivalent laboratory required), that underwent standard radiation therapy.
• The following eligibility criteria apply to strata A, B and C:
• The patient must test positive for HLA-A\*02:01 (positive testing from a CLIA or equivalent laboratory required; only the HLA A\*02:01 subtype is eligible; other subtypes are excluded)
• The patient must be either off systemic steroids or be on stable dose of dexamethasone or equivalent (max 0.1 mg/kg/day; maximum 4mg/day) at time of enrollment.
• Patients must not have received any prior chemotherapy, immunotherapy or bone marrow transplant for the treatment of their tumor. Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg/m\^2/dose continuously during radiation therapy for 42 days) or dexamethasone is allowed.
• Patients must have undergone radiation therapy and surgery as part of their standard of care.
• Stratum A: Radiation therapy must have started within 4 weeks of diagnosis by imaging or surgery, whichever is later.
• Stratum B: For subjects undergoing surgery for more extensive resection, radiation therapy should be started within 4-6 weeks from surgery.
• Stratum C: Radiation therapy must have started within 4 weeks of diagnosis by imaging or surgery, whichever is later. For subjects undergoing surgery for more extensive resection, radiation therapy should be started within 4-6 weeks from surgery.
• Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients \< 16 years of age (See Appendix A). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

You may not qualify if:

• Investigational Drugs
• Patients who are currently receiving another investigational drug are not eligible.
• Prior treatment with another investigational drug.
• Anti-cancer Agents
• Patients who are currently receiving other anti-cancer agents are not eligible.
• Prior treatment with other anti-cancer agents.
• Patients who have received a live / attenuated vaccine within 30 days of first treatment.
• Patients with evidence of disseminated or leptomeningeal disease.
• Patients with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible. Note: Patients that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair.
• Patients with a ≥ Grade 2 hypothyroidism due to history of autoimmunity are not eligible. (Note: Hypothyroidism due to previous irradiation or thyroidectomy will not impact eligibility).
• Patients who have received prior solid organ or bone marrow transplantation are not eligible.
• Patients with uncontrolled infection.
• Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).

Sponsors & Collaborators

• Sabine Mueller, MD, PhD: lead
• The V Foundation for Cancer Research: collaborator
• Pacific Pediatric Neuro-Oncology Consortium: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (15)

Rady Children's Hospital-San Diego

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The University Children's Hospital in Zurich

Zurich, Canton of Zurich, 8032, Switzerland

Location

Related Publications (1)

• Mueller S, Taitt JM, Villanueva-Meyer JE, Bonner ER, Nejo T, Lulla RR, Goldman S, Banerjee A, Chi SN, Whipple NS, Crawford JR, Gauvain K, Nazemi KJ, Watchmaker PB, Almeida ND, Okada K, Salazar AM, Gilbert RD, Nazarian J, Molinaro AM, Butterfield LH, Prados MD, Okada H. Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. J Clin Invest. 2020 Dec 1;130(12):6325-6337. doi: 10.1172/JCI140378.

  PMID: 32817593 DERIVED

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Glioma

Interventions

Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Sabine Mueller, MD PhD
• Organization: University of California, San Francisco

Sabine.Mueller@ucsf.edu

(415) 502-1600

Study Officials

• Sabine Mueller, MD, PhD, MAS

  University of California, San Francisco

  STUDY CHAIR

• Hideho Okada, MD, PhD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 9, 2016
• Study Start: November 18, 2016
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); CH (1)