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Diffuse Intrinsic Pontine GliomaPhase 1/2NCT02960230

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

A Phase 1/2 study testing K27M peptide and Nivolumab in people with Diffuse Intrinsic Pontine Glioma and Glioma, run by Sabine Mueller, MD, PhD at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 3 to 21 years
What is being tested?
K27M peptide and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
15 sitesin 2 countries
Study dates
18 Nov 2016to 31 Dec 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.
  • The patient must have adequate organ function defined as
  • Adequate Bone Marrow Function Defined as:
  • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and
  • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
  • Adequate Renal Function Defined as:
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2 or
  • A serum creatinine based on age/gender as follows:
  • Age Maximum Serum Creatinine (mg/dL) Male Female 3 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC).
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age and
  • serum glutamic-pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT) ≤ 110 U/L and
  • Serum albumin ≥ 2 g/dL.
  • Adequate Pancreatic Function Defined as:
  • Serum lipase ≤ ULN at baseline.
  • Adequate Pulmonary Function Defined as:
  • No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of > 92% while breathing room air.
  • Adequate Neurologic Function Defined as:
  • Patients with seizure disorder may be enrolled if seizure disorder is well controlled.
  • The effects of the H3.3K27M vaccine and nivolumab on the developing human fetus are unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception. Adequate methods include: hormonal or barrier method of birth control; or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation.
  • Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the subjects age.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

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

    Chicago, Illinois, 60611

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Texas Children's Hospital

    Houston, Texas, 77030

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospitals and Clinics of Minnesota

    Minneapolis, Minnesota, 55455

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Utah

    Salt Lake City, Utah, 84112

  • Rady Children's Hospital-San Diego

    San Diego, California, 92123

  • University of California, San Francisco

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • St. Louis Children's Hospital

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Switzerland1 site

  • The University Children's Hospital in Zurich

    Zurich, Canton of Zurich, 8032

Other trials in Switzerland

About this study

Official title: H3.3K27M Specific Peptide Vaccine Combined With Poly-ICLC With and Without PD-1 Inhibition Using Nivolumab for the Treatment of Newly Diagnosed HLA-A2 (02:01)+ H3.3K27M Positive Diffuse Intrinsic Pontine Glioma (DIPG) and Newly Diagnosed HLA-A2 (02:01)+ H3.3K27M Positive Gliomas

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.

Read the detailed description

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.

Being tested
K27M peptide, Nivolumab
Keywords
peptide vaccine, immunotherapy, DIPG, vaccine, nivolumab
Medical subject headings
Diffuse Intrinsic Pontine Glioma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • K27M peptideBiological

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

  • NivolumabDrug

    Also called Keytruda

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

Study groups in NCT02960230
Study groupRoleWhat they receive
Stratum A: Newly Diagnosed DIPGExperimentalNewly 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.
Receives: Biological: K27M peptide
Stratum B: Newly Diagnosed Glioma (non-DIPG)ExperimentalNewly 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.
Receives: Biological: K27M peptide
Stratum C: Newly Diagnosed DIPG or other Midline GliomaExperimentalNewly 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.
Receives: Biological: K27M peptide; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 months

  2. 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.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2016 (estimated)
  2. Study start18 Nov 2016
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02960230
Sponsor's protocol ID
PNOC 007
Other IDs
150819, NCI-2017-01830, CA209-8TX
Status last verified
Dec 2024
First submitted
2 Nov 2016
Last updated
22 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32817593

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing K27M peptide and Nivolumab in people with Diffuse Intrinsic Pontine Glioma and Glioma, run by Sabine Mueller, MD, PhD at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Adverse Events (AE) Related to Treatment (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02960230, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.

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