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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
University of California, San Francisco
San Francisco, California, United States
RECRUITINGFrequency 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
Time frame: Up to 28 days following infusion of autologous anti-H3.3K27M TCR-expressing T-cells (KIND T cells)
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
Time frame: Up to 24 months
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
Time frame: Up to 12 months
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.
Time frame: Up to 12 months
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