Patients will receive 3 cycles of NK cell infusions over 12 weeks. Each cycle will consist of 1 infusion per week for 3 weeks, followed by a rest week (week 4). Dose will be escalated in an inter-patient stepwise fashion consisting of 4 dose levels.
Name: NK cells
Description: To identify the incidence of adverse events from autologous natural killer cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via Ommaya reservoir in patients with recurrent high-grade glioma. This will be evaluated using the CTCAE version 5
Measure: Incidence of adverse events from NK cells Time: 36 monthsDescription: To establish the maximum tolerated dose (MTD) of autologous natural killer cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via Ommaya reservoir in patients with recurrent high-grade glioma. MTD will be the maximum dose at which fewer than one-third of patients experience a dose-limiting toxicity during cycle 1 of therapy
Measure: Maximum tolerated dose Time: 36 monthsDescription: To determine the overall survival, defined as the percentage of patients in the study who are alive at 6 months following start of treatment
Measure: Overall survival Time: 6 monthsDescription: To assess the antitumor activity based on imaging and cytology of autologous NK cell administration directly into the tumor or the resection cavity.
Measure: NK cell antitumor activity Time: 36 monthsDescription: NK cell phenotypes will be measured by mass cytometry (unit of measure= % of nucleated cells)
Measure: Assessment of the immuno-phenotype of expanded NK cells for high-grade glioma patients Time: 36 monthsDescription: NK cell functional potency will be measured as cytotoxicity by calcien- AM cytotoxicity assays (unit of measure= % of patietns with complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), or progressive disease (PD) with calculated 95% confidence intervals)
Measure: Assessment of function of expanded NK cells for high-grade glioma patients Time: 36 monthsDescription: To determine the immune signature-based profile of each patient's tumor as assayed by the NanoString PanCancer IO360 panel
Measure: Assessment of the immune signature based profile Time: 36 monthsDescription: To determine the o6-methylguanine-DNA-methyltransferase (MGMT) methylation and mutation status of BRAF V600E, ACVR1, ATRX, TP53, H3.3 G34, H3.3/ H3.1 K27 and IDH1, along with the presence or absence of 9p21 (CDKN2A) homozygous deletion as well as PDGFR amplification
Measure: Determination of genetic changes on high-grade gliomas Time: 36 monthsDescription: To determine changes in the TCR repertoire diversity using a Nanostring custom reagent that evaluates the VDJ sequences present before and after NK cell treatment.
Measure: Changes of the T-cell Receptor Repertoires Time: 36 monthsAllocation: N/A
Single Group Assignment
There is one SNP
To determine the o6-methylguanine-DNA-methyltransferase (MGMT) methylation and mutation status of BRAF V600E, ACVR1, ATRX, TP53, H3.3 G34, H3.3/ H3.1 K27 and IDH1, along with the presence or absence of 9p21 (CDKN2A) homozygous deletion as well as PDGFR amplification. --- V600E ---