NCT05478837

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

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

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 2 Years – 25 Years
• Healthy volunteers: Not accepted

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. 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).

Detailed description

PRIMARY OBJECTIVES: I. 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: I. To evaluate manufacturing feasibility of KIND T cells. II. To characterize KIND T cells with respect to their expansion and persistence. EXPLORATORY OBJECTIVES: I. 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. V. 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.

Conditions

• Diffuse Midline Glioma, H3 K27M-Mutant

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
BIOLOGICAL	Autologous Anti-H3.3K27M TCR-expressing T-cells	Given IV

Timeline

• Start date: 2023-07-20
• Primary completion: 2029-08-31
• Completion: 2029-08-31
• First posted: 2022-07-28
• Last updated: 2026-03-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study