Genetically Modified Cells (KIND T Cells) for the Treatment of HLA-A*0201-Positive Patients With H3.3K27M-Mutated Glioma (PNOC018)
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|ClinicalTrials.gov Identifier: NCT05478837|
Recruitment Status : Not yet recruiting
First Posted : July 28, 2022
Last Update Posted : November 10, 2022
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Midline Glioma, H3 K27M-Mutant||Drug: Cyclophosphamide Drug: Fludarabine Biological: Autologous Anti-H3.3K27M TCR-expressing T-cells||Phase 1|
I. To determine the maximum tolerated dose (MTD) 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 safety profile of a single intravenous (IV) infusion of KIND T cells in HLA-A*0201+ participants with H3.3K27M+ diffuse midline gliomas.
I. To evaluate manufacturing feasibility of KIND T cells.
II. To characterize KIND T cells with respect to their expansion and persistence.
I. To describe anti-tumor 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 adverse events (AEs).
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 (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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 Newly Diagnosed H3.3K27M-positive Diffuse Midline Gliomas|
|Estimated Study Start Date :||January 1, 2023|
|Estimated Primary Completion Date :||December 31, 2028|
|Estimated Study Completion Date :||December 31, 2028|
Experimental: Treatment (KIND T cells, cyclophosphamide, fludarabine)
Patients 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.
Other Name: Fludara
Biological: Autologous Anti-H3.3K27M TCR-expressing T-cells
Other Name: KIND T cells
- Maximum tolerated dose (MTD) [ Time Frame: Up to 28 days following infusion of autologous anti-H3.3K27M TCR-expressing T-cells (KIND T cells) ]MTD is defined as the dose at which fewer than one-third of participants experience a dose limiting toxicity (DLT) for all participants who received at least one study intervention.
- Number of participants with treatment-emergent adverse events [ Time Frame: Up to 24 months ]Treatment-emergent adverse events will be graded according to severity, and their incidence will be summarized by dose level.
- Percentage of participants who receive KIND T cells [ Time Frame: Up to 12 months ]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
- Duration of KIND T cells in-vivo persistence [ Time Frame: Up to 12 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05478837
|Contact: Jenna Weight||415-502-1600||PNOC018@ucsf.edu|
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|Contact: Jenna Weight 415-502-1600 PNOC018@ucsf.edu|
|Principal Investigator: Sabine Mueller, MD, PhD, MAS|
|Principal Investigator:||Sabine Mueller, MD, PhD, MAS||University of California, San Francisco|
|Study Chair:||Hideho Okada, MD, PhD||University of California, San Francisco|