NCT04991870

Phase I CB-NK-TGF-ßR2-/NR3C1- in rGBM

A Phase I Clinical Trial With a Window-of-Opportunity Component of Engineered NK Cells Containing Deleted TGF-ßR2 and NR3C1 in Recurrent Grade 4 Astrocytoma (Glioblastoma)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is to find out the best dose, possible benefits and/or side effects of engineered natural killer (NK) cells containing deleted TGF-betaR2 and NR3C1 (cord blood \[CB\]-NK-TGF-betaR2-/NR3C1-) in treating patients with glioblastoma that has come back (recurrent). CB-NK-TGF-betaR2-/NR3C1- cells are genetically changed immune cells that may help to control the disease.

Detailed description

PRIMARY OBJECTIVES: * To determine the safety and tolerability of intratumoral injection of escalating doses of allogeneic CB-NK-TGF-£\]R2-/NR3C1- in patients with recurrent grade 4 astrocytoma, * To determine the maximum tolerated dose (MTD) and the occurrence of dose limiting toxicities (DLTs) (Group 1) of CB-NK-TGF-£\]R2-/NR3C1- administered via IT injection in patients with recurrent grade 4 astrocytoma * To evaluate the immunological phenotype and anti-tumor function of NK cells in resected tumor tissue after treatment with CB-NK-TGF-âR2-/NR3C1- in the surgical expansion group (Group 2). Persistency of the NK cells in the tissue will be assessed by flow cytometry. Tissue cells will be stained with anti human CD45, anti human CD56 and anti HLA molecule expressed by the cord blood donor infused in the patient. NK cells from the tissue may be isolated using magnetic bead selection (anti-HLA specific from cord blood donor labeled with PE and them use a anti PE magnetics bead selection). Those NK cells would be used to perform a chromium release assay (killing assay) to test the ability of the NK in killing K562 and GSC targets. If the NK cells obtained from the tissue are too low to do killing assay, the NK cells could be expanded for one week using UAPC and IL2 to get more NK cells for assays. SECONDARY OBJECTIVE: -To determine response as measured by Response Assessment in Neuro-Oncology (RANO), duration of clinical response, progression free survival (PFS), time to progression (TTP), and overall survival (OS)ƒn EXPLORATORY OBJECTIVES: -Monitoring immune responses following CB-NK-TGF-£\]R2-/NR3C1- dosing, in vivo persistence and expansion of CB-NK-TGF-£\]R2-/NR3C1- during treatment, characterization of immune cell subpopulations in the peripheral blood, serum analysis of immune correlates, alloreactivity characterization, and anti-HLA antibody analysis, and CB-NK-TGF-£\]R2-/NR3C1- trafficking in tumor microenvironments in the surgical expansion cohort. Tumor tissue from surgical resection will be further analyzed for immune infiltrates, fibrosis, and tumor microenvironment.

Conditions

• Recurrent Gliosarcoma
• Recurrent Supratentorial Glioblastoma
• Supratentorial Gliosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	Cord Blood-derived Expanded Allogeneic Natural Killer Cells	Given CB-NK-TGF-betaR2-/NR3C1- intratumorally
PROCEDURE	Resection	Undergo surgical resection

Timeline

• Start date: 2023-04-28
• Primary completion: 2027-01-31
• Completion: 2027-01-31
• First posted: 2021-08-05
• Last updated: 2026-01-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study