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Diffuse Intrinsic Pontine GliomaPhase 1ENACTINGNCT04749641

Neoantigen Vaccine Therapy Against H3.3-K27M Diffuse Intrinsic Pontine Glioma

A Phase 1 study testing Histone H3.3-K27M Neoantigen Vaccine Therapy in people with Diffuse Intrinsic Pontine Glioma, run by Yang Zhang at 1 site in China.

Completed

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

Official record
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Trial summary

Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy remains the current standard-of-care treatment that is minimal effective. Read more about this study

Who is it for?
Ages 5 years and olderHealthy volunteers can take part
Conditions the study is for
Diffuse Intrinsic Pontine Glioma
What is being tested?
Histone H3.3-K27M Neoantigen Vaccine Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteChina
Study dates
8 Mar 2021to 14 Oct 2024
Phase
Phase 1
Are there results?
None posted in the registry

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 5 years and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • First entry criteria
  • Age ≥ 5 years old;
  • Newly-diagnosed patients with DIPG appearance on MRI image;
  • HLA-A2 subtype;
  • The expected survival time exceeds 24 weeks;
  • The KPS score is greater than 50; B. Second entry criteria
  • 1. The KPS score is greater than 50; 2. DIPG is diagnosed histologically on tumor tissue obtained by biopsy or surgical resection; 3. H3.3K27M mutation is detected on tumor tissue obtained by biopsy or surgical resection ; 4. Adequate organ functions that meet the following criteria: The absolute number of neutrophils: ≥1500/mm3 Platelet count: ≥75000/uL Hemoglobin: ≥80 g/L Creatinine≤1.5×ULN Bilirubin≤1.5×ULN ALT≤3×ULN AST≤3×ULN 5. Ability to comprehend and sign an informed consent form.

Who cannot join

  • With past medical history of malignant tumors (except being asymptomatic for more than 3 years);
  • History of allergy to chemotherapeutics or radiosensitizers for the treatment of cancer in central nervous system and head/neck;
  • History of allergy to the vaccine and its ingredients;
  • Comorbidity with HIV infection and/or acute phase of hepatitis B/C;
  • Any progressive diseases that hinder participation in the trial;
  • With unstable cardiovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia et.al.;
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  • History of uncontrolled mental illnesses;
  • Inability to comprehend or sign informed consent form or abide by the research procedures;
  • Other conditions believed to hinder participation in this trial at investigator' discretion.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Beijing Tiantan Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100070

Other trials in China

About this study

Official title: Enhanced Histone H3.3-K27M Neoantigen Vaccine Therapy Against Diffuse Intrinsic Pontine Glioma (ENACTING)- A Phase I Clinical Trial

Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy remains the current standard-of-care treatment that is minimal effective. Thus, the median overall survival after diagnosis is just 10 months. Recent studies have identified a lysine 27-to-methionine (K27M) somatic mutation at histone H3 variant (H3.3), as a feature mutation in DIPGs. Several preclinical studies have already demonstrated H3.3-K27M as a promising target for immunotherapy. The researched vaccine is a cancer-treatment vaccine containing an H3.3-K27M targeted neoantigen peptide, that can be taken up by antigen-presenting cells (APCs). APCs can present the peptide with the major histocompatibility complex (MHC) molecules on cell surface, thereby activating neoantigen-specific T cells and triggering corresponding cytotoxic T cell immune responses to eliminate H3.3-K27M-expressing DIPG cells. The main goal of this study is investigating the safety and preliminary efficacy of the vaccine in treating newly-diagnosed DIPGs when the vaccine is administered in combination with the standard-of-care treatment.

Being tested
Histone H3.3-K27M Neoantigen Vaccine Therapy
Medical subject headings
Diffuse Intrinsic Pontine Glioma

What participants receive

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

  • Histone H3.3-K27M Neoantigen Vaccine TherapyBiological

    The researched vaccine, containing H3.3-K27M-targeting neoantigen peptides and poly ICLC, will be administered through subcutaneous injection into DIPG patients after they complete surgical/stereotactic biopsy and conformal radiotherapy. The day of first vaccine injection is defined as D1 (day 1), and then the injections will be administered on D3, D15, Day 29, Day 57, Day 85 and one injection every 8 weeks thereafter. In order to determine the Maximum Tolerated Dose (MTD) of the vaccine, a "6+3" dose escalation design is applied. There are three doses for the vaccine. Dose 1: 0.5mg peptide + Poly ICLC; Dose 2: 1mg peptide + Poly ICLC; Dose 3: 2mg peptide + Poly ICLC.

Study groups in NCT04749641
Study groupRoleWhat they receive
Open surgical biopsyExperimentalA total of 15 subjects with open surgical biopsy indications will receive microsurgical resection, followed by conformal radiotherapy and administration of the researched vaccine.
Receives: Biological: Histone H3.3-K27M Neoantigen Vaccine Therapy
Stereotactic biopsyExperimentalA total of 15 subjects without open surgical biopsy indications will receive stereotactic biopsy, followed by conformal radiotherapy and administration of the researched vaccine.
Receives: Biological: Histone H3.3-K27M Neoantigen Vaccine Therapy

What is being measured

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

  1. Safety of histone H3.3-K27M neoantigen vaccine in treating newly diagnosed DIPGs

    AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Measured: All the Adverse events (AEs) were recorded until 24 weeks after the last shot

  2. Rate of the patients who survive for more than one year after surgery/biopsy in all the DIPG patients who receive H3.3-K27M neoantigen vaccine

    One-year survival rate

    Measured: One year after surgery or biopsy

Secondary outcomes (5)

  1. Maximum Tolerated Dose of H3.3-K27M neoantigen vaccine to treat DIPGs

    ">= Grade 3 " vaccine related AEs are defined as DLTs. In order to determine the Maximum Tolerated Dose (MTD) of the vaccine, a "6+3" dose escalation design is applied.

    Measured: DLTs were monitored at timepoints of every vaccine shot until the 28th day after the first injection

  2. Rate of the patients who survive for more than two years after surgery/biopsy in all the DIPG patients who receive H3.3-K27M neoantigen vaccine

    two-year survival rate

    Measured: two years after surgery or biopsy

  3. Median Progression-free survival time of the DIPG patients who receive H3.3-K27M neoantigen vaccine

    Progression-free survival time: the time from operation/biopsy to progression (when shows signs or symptoms of the growth or the spreading of a tumor)

    Measured: start 4 weeks after the first shot and every 8 weeks until disease progression

  4. Median Overall survival time of the DIPG patients who receive H3.3-K27M neoantigen vaccine

    overall survival time: the time from operation/biopsy to death.

    Measured: start 4 weeks after the first shot and every 8 weeks until death

  5. Immunological effectiveness of H3.3-K27M neoantigen vaccine for the treatment of DIPG patients

    Immunological effectiveness is measured by an IFN-γ ELISPOT assay as number of spot-forming cells in one million peripheral blood mononuclear cells.

    Measured: baseline 1: pre-radiotherapy; baseline 2: immediately after completing radiotherapy; Day 15, Day 57, Day 85 and every 8 weeks thereafter until up to 2 years after the first shot.

Timeline

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

  1. First posted11 Feb 2021
  2. Study start8 Mar 2021
  3. Primary completion14 Oct 2024
  4. Study completion14 Oct 2024

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04749641
Sponsor's protocol ID
KY 2019-126-01
Acronym
ENACTING
Status last verified
Jun 2025
First submitted
3 Feb 2021
Last updated
6 Jun 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Histone H3.3-K27M Neoantigen Vaccine Therapy in people with Diffuse Intrinsic Pontine Glioma, run by Yang Zhang at 1 site in China.

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 7 inclusion and 9 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 6 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety of histone H3.3-K27M neoantigen vaccine in treating newly diagnosed DIPGs (time frame: All the Adverse events (AEs) were recorded until 24 weeks after the last shot). 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 NCT04749641.

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 6 Jun 2025.

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