Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Given CB-NK-TGF-betaR2-/NR3C1- intratumorally

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).

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.

Live record on ClinicalTrials.gov →

• Signed and dated informed consent.
• Male or female participants aged ≥ 12 years on the day of signing informed consent.
• Has histologically confirmed supratentorial World Health Organization grade 4 recurrent astrocytoma to include recurrent IDH WT glioblastoma or gliosarcoma and recurrent IDHmutant grade 4 astrocytoma, and recurrent gliosarcoma with any prior number of recurrences, and who have received prior radiation and temozolomide therapy. Participants will be eligible if the original histology was lower-grade glioma grade 2 or 3 and a subsequent histological diagnosis of recurrent glioblastoma or IDH-mutant grade 4 astrocytoma is made.
• Karnofsky Performance Score (KPS) of \>70 at trial entry. Lansky \>70 at trial entry for patients less than 16.
• Must be at least 12 weeks from receiving conformal radiation, unless RANO criteria for early progression are met.
• A baseline brain MRI with Advance Brain Tumor Imaging (ABTI) must be obtained no more than 30 days prior to study registration

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.