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Diffuse Midline Glioma, H3 K27M-MutantPhase 1PNOC018NCT05478837

Genetically Modified Cells (KIND T Cells) for the Treatment of HLA-A*0201-Positive Patients With H3.3K27M-Mutated Glioma

A Phase 1 study testing Cyclophosphamide, Fludarabine and Autologous Anti-H3.3K27M TCR-expressing T-cells in people with Diffuse Midline Glioma, H3 K27M-Mutant, run by University of California, San Francisco at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I, first-in-human trial tests the safety, side effects, and best dose of genetically modified cells called KIND T cells after lymphodepletion (a short dose of chemotherapy) in treating patients who are HLA-A*0201-positive and have H3.3K27M-mutated diffuse midline glioma. Read more about this study

Who is it for?
Ages 2 to 25 years
Conditions the study is for
Diffuse Midline Glioma, H3 K27M-Mutant
What is being tested?
Cyclophosphamide, Fludarabine and Autologous Anti-H3.3K27M TCR-expressing T-cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
20 Jul 2023to 31 Jan 2026
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 2 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participants 2 to 25 years of age inclusive, at the time of signing the informed consent. The first two participants will be 12-25 years of age.
  • Male participants of impregnate potential must agree to use contraception, during the study and for at least 6 months after the last study intervention and refrain from donating sperm during this period.
  • Female participants of childbearing potential must agree to follow the contraceptive guidance, during the study and for at least 6 months after the last study intervention.
  • Females of childbearing potential must have a negative serum or urine pregnancy test within 14 days of receiving study interventions.
  • CNS reservoir such as Ommaya catheter must be in place.
  • Patients must be enrolled on PNOC COMP prior to enrollment on PNOC018 if PNOC COMP is open to accrual at the enrolling institution.
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  • Participants with DMG who are positive for the H3.3K27M mutation (positive testing from a Clinical Laboratory Improvement Amendments (CLIA) laboratory required or equivalent) and who completed at least standard radiation therapy.
  • All participants must test positive for HLA-A*0201 (positive testing from a CLIA or equivalent laboratory required). Other HLA-A2 subtypes are excluded.
  • All participants must consent for tumor tissue (fresh or archival) for biomarker analysis if available.
  • All participants must have evaluable or measurable disease at the time of consent.
  • All participants must be either off systemic steroids or be on a stable or declining dose of dexamethasone (maximum dose of 0.1 mg/kg/day or 4 mg/day) at the time of enrollment.
  • Participants must not have received any bone marrow transplants for the treatment of their tumor.
  • Participants must discontinue all anti-cancer agents and radiotherapy and, must have recovered from significant acute toxic effects of prior therapies.
  • Chemotherapy/biologic therapy: All cytotoxic chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment.
  • Immunotherapy: The last dose of anti-tumor antibody therapy must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment.
  • All participants must have adequate organ function.
  • Adequate bone marrow function is defined as:
  • Peripheral absolute neutrophil account 1000/mm^3 and
  • Platelet count 100,000/mm^3 (transfusion dependent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Absolute lymphocyte count >= 500/µL or CD3 count of >= 150/µL
  • Adequate renal function is defined as:
  • Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2 or
  • Maximum serum creatinine based on age/gender as follows:
  • 3 to < 6 years =< 0.8 mg/dL (male and female)
  • 6 to < 10 years =< 1.0 mg/dL (male and female)
  • 10 to < 13 years =< 1.2 mg/dL (male and female)
  • 13 to < 16 years =< 1.5 mg/dL (male) and 1.4 mg/dL (female)
  • >= 16 years =< 1.7 mg/dL (male) and 1.4 mg/dL (female)
  • Adequate liver function is defined as:
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age and
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN and
  • Serum albumin >= 2 g/dL
  • Participants with a history of congestive heart failure at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must have adequate cardiac function as clinically indicated. Only order ECHO and EKG for patients with history of cardiac toxicity.
  • (QTc) =< 480 ms
  • Injection fraction >= 45% by echocardiogram
  • Adequate pulmonary function is defined as no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and pulse oximetry > 92% while breathing room air
  • Adequate neurologic function is defined as a well-controlled seizure disorder and performance status (Lansky < 16 years and Karnofsky >= 16 years) that is at least 60.
  • Informed consent: Capable of giving signed informed consent or assent depending on participant age as appropriate which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Assent will be obtained when appropriate based on the subjects age.

Who cannot join

  • Participants are excluded from the study if any of the following criteria apply:
  • Participants with MRI or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect should be made by the study investigators prior to any planned KIND T cell treatment. Pre-infusions MRI will need to be reviewed by the study investigators prior to dosing. Participants with an assessment score >= 3 will be excluded, based on Table 4 in section 3.8.2
  • Participants with a known disorder that affects their immune system such as HIV or hepatitis B or C, or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy. Participants who are currently using inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily excluded from the study.
  • Participants who have received prior solid organ or bone marrow transplantation.
  • Participants with uncontrolled infection.
  • Female participants of childbearing potential must not be pregnant or breast-feeding.
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Untreated symptomatic hydrocephalus determined by treating physician.
  • Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
  • Participants who are currently receiving another investigational drug.
  • Participants who are co-enrolled on another investigational protocol.
  • Participants who are currently receiving other anticancer agents (bevacizumab used to treat tumor mass effect will not constitute an exclusion; at time of enrollment participants need to be off bevacizumab and will need to be discussed with the study team).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: PNOC018 A Phase 1 Clinical Trial of Autologous T Cells Expressing a TCR Specific for H3.3K27M With Inhibition of Endogenous TCR (KIND T Cells) in HLA-A*0201-positive Participants With H3.3K27M-positive Diffuse Midline Gliomas

This phase I, first-in-human trial tests the safety, side effects, and best dose of genetically modified cells called KIND T cells after lymphodepletion (a short dose of chemotherapy) in treating patients who are HLA-A*0201-positive and have H3.3K27M-mutated diffuse midline glioma. KIND T cells are a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory into KIND T cells so they will recognize certain markers found in tumor cells. Drugs such as cyclophosphamide and fludarabine are chemotherapy drugs used to decrease the number of T cells in the body to make room for KIND T cells. Giving KIND T cells after cyclophosphamide and fludarabine may be more useful against cancer compared to the usual treatment for patients with H3.3K27M-mutated diffuse midline glioma (DMG).

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and tolerability of a single intravenous (IV) infusion of autologous anti-H3.3K27M T-cell receptor (TCR) -expressing T-cells (KIND T cells) in HLA-A*0201+ participants with H3.3K27M+ diffuse midline gliomas.

II. To determine the feasibility of a single intravenous (IV) infusion of KIND T cells in HLA-A*0201+ participants with H3.3K27M+ diffuse midline gliomas.

SECONDARY OBJECTIVES:

  1. To evaluate manufacturing feasibility of KIND T cells. II. To characterize KIND T cells with respect to their expansion and persistence.

EXPLORATORY OBJECTIVES:

  1. To describe antitumor responses and survival after infusion of KIND T cells

II. To explore the association of tumor and immune biomarkers including but not limited to characterization of KIND T cells in blood and tumor samples with clinical endpoints and/or AEs

III. To assess Health-Related Quality of Life (HRQoL) in patients newly diagnosed with HLA-A*0201+ H3.3K27M+ DMG.

IV. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks.

  1. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks.

OUTLINE: This is a dose-escalation study of KIND T cells.

CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) on days -4, -3, and -2 and cyclophosphamide IV on day -2 in the absence of disease progression or unacceptable toxicity.

T CELL THERAPY: Patients receive KIND T cells IV over 10 minutes on day 0.

After completion of study treatment, patients are followed up at day 1, 3, 7, 10, 14, 21, and 28, weeks 8-24 and 28-92, months 24-36, and then yearly until year 15.

Being tested
Cyclophosphamide, Fludarabine, Autologous Anti-H3.3K27M TCR-expressing T-cells
Keywords
Autologous T Cells, KIND T Cells, HLA-A*0201-Positive

What participants receive

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

  • CyclophosphamideDrug

    Also called Cytoxan, Cycloblastin

    Given IV

  • FludarabineDrug

    Also called Fludara

    Given IV

  • Autologous Anti-H3.3K27M TCR-expressing T-cellsBiological

    Also called KIND T cells

    Given IV

Study groups in NCT05478837
Study groupRoleWhat they receive
Treatment (KIND T cells, cyclophosphamide, fludarabine)ExperimentalPatients receive fludarabine IV on days -4, -3, and -2 and cyclophosphamide IV on day -2 in the absence of disease progression or unacceptable toxicity for the conditioning regimen. Patients also receive KIND T cells IV at dose level 1 (2 x 106 dextramer®+ CD8+ cells/kg) on day 0. If no DLTs are reported, newly enrolling participants may receive dose level 2 of KIND T cells on day 0.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Autologous Anti-H3.3K27M TCR-expressing T-cells

What is being measured

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

  1. Frequency and severity of adverse events

    To determine the safety and tolerability of a single intravenous (IV) infusion of KIND T cells in HLA A*0201+ participants with H3.3K27M+ diffuse midline gliomas

    Measured: Up to 28 days following infusion of autologous anti-H3.3K27M TCR-expressing T-cells (KIND T cells)

  2. Percent of successfully manufactured KIND T cells

    To determine feasibility of a single intravenous (IV) infusion of KIND T cells in HLA A*0201+ participants with H3.3K27M+ diffuse midline gliomas

    Measured: Up to 24 months

Secondary outcomes (2)

  1. Percentage of participants who receive KIND T cells

    The percentage of participants who received KIND T cell infusions will be reported. If the manufacturing of T-cell product is not successful because it does not meet release criteria, the participant will have the choice of a second apheresis for a second manufacturing process

    Measured: Up to 12 months

  2. Duration of KIND T cells in-vivo persistence

    The duration of KIND T cells in-vivo persistence will be estimated using Kaplan-Meier techniques. In addition, the persistence of KIND T cells will be evaluated for each participant for up to 12 months or until any 2 sequential negative tests documenting loss of KIND T cells in blood.

    Measured: Up to 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 posted28 Jul 2022
  2. Study start20 Jul 2023
  3. Primary completion31 Jan 2026
  4. Study completion31 Jan 2026

Why it stopped: Logistical issues

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
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05478837
Sponsor's protocol ID
210813
Other IDs
NCI-2022-05420, PICI0029
Acronym
PNOC018
Status last verified
Jul 2026
First submitted
26 Jul 2022
Last updated
13 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data after de-identification.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and Autologous Anti-H3.3K27M TCR-expressing T-cells in people with Diffuse Midline Glioma, H3 K27M-Mutant, run by University of California, San Francisco at 1 site in United States.

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 38 inclusion and 12 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: stopped early, as of the sponsor's last update on 13 Jul 2026. 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 United States. 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 was stopped early (reason given: Logistical issues). Results are not available in the source record.

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?

Frequency and severity of adverse events (time frame: Up to 28 days following infusion of autologous anti-H3.3K27M TCR-expressing T-cells (KIND T cells)). 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 NCT05478837.

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 13 Jul 2026.

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