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Nervous System Neoplasms

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Enrolled patients must proceed to surgery for tumor resection and Ommaya placement into the resection cavity within 14 days of enrollment. Starting dose of 3x10\^6/m\^2 of TGFβi NK cells (first dose) may be administered at least 14 days after the Ommaya reservoir placement, and may not start until all acute surgical complications have resolved (maximum of 6 weeks after enrollment). TGFβi NK cell infusions through the Ommaya reservoir will occur once weekly for three weeks followed by one rest week. If patients have stable or improved disease, patients may continue to receive therapy for a total of 12 cycles.

If no safety or toxicity events are demonstrated by the starting dose cohort, enrolled patients in the next dosing cohort must proceed to surgery for tumor resection and Ommaya placement into the resection cavity within 14 days of enrollment. The dose of 3x10\^7/m\^2 of TGFβi NK cells (first dose) may be administered at least 14 days after the Ommaya reservoir placement, and may not start until all acute surgical complications have resolved (maximum of 6 weeks after enrollment). TGFβi NK cell infusions through the Ommaya reservoir will occur once weekly for three weeks followed by one rest week. If patients have stable or improved disease, patients may continue to receive therapy for a total of 12 cycles.

If no safety or toxicity events are demonstrated by the previous dose cohort, enrolled patients in the next dosing cohort must proceed to surgery for tumor resection and Ommaya placement into the resection cavity within 14 days of enrollment. The dose of 3x10\^8/m\^2 of TGFβi NK cells (first dose) may be administered at least 14 days after the Ommaya reservoir placement, and may not start until all acute surgical complications have resolved (maximum of 6 weeks after enrollment). TGFβi NK cell infusions through the Ommaya reservoir will occur once weekly for three weeks followed by one rest week. If patients have stable or improved disease, patients may continue to receive therapy for a total of 12 cycles.

The TGFβi NK cell product will be manufactured in the Cell Therapy Laboratory at Nationwide Children's Hospital and given via infusion.

Universal Donor (UD) Transforming growth factor beta imprinting (TGFβi) Natural Killer (NK) Cells

Implantation

Aubrie Dreschler

Aubrie Drechsler

Sabine Mueller, MD, PhD

This phase I trial tests the safety, side effects, and best dose of ex vivo expanded natural killer cells in treating patients with cancerous (malignant) tumors affecting the upper part of the brain (supratentorial) that have come back (recurrent) or that are growing, spreading, or getting worse (progressive). Natural killer (NK) cells are immune cells that recognize and get rid of abnormal cells in the body, including tumor cells and cells infected by viruses. NK cells have been shown to kill different types of cancer, including brain tumors in laboratory settings. Giving NK cells from unrelated donors who are screened for optimal cell qualities and determined to be safe and healthy may be effective in treating supratentorial malignant brain tumors in children and young adults.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of natural killer (NK) cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via an Ommaya reservoir in patients with recurrent or progressive supratentorial malignant brain tumors.

II. To determine the recommended phase 2 dose (RP2D) for natural killer (NK) cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via an Ommaya reservoir in patients with recurrent or progressive supratentorial malignant brain tumors.

EXPLORATORY OBJECTIVES:

I. To determine the 6 months overall survival (OS), defined as the percentage of patients in the study who are alive at 6 months following start of treatment.

II. To determine the persistence, immuno-phenotype and function of adoptively-transferred expanded NK cells, and correlate the findings with the overall response.

III. To determine the immune signature-based profile of each patient's tumor. IV. To determine changes in the T-cell receptor (TCR) repertoire diversity before and after Transforming growth factor beta imprinted (TGFβi) NK cell treatment.

V. To evaluate the effect of systemic steroids on the persistence and efficacy of TGFβi NK cells.

VI. To assess Quality of Life (QOL) and cognitive measures in children and young adults with recurrent or progressive supratentorial malignant brain tumors.

OUTLINE: This is a dose-escalation study.

Participants undergo placement of an Ommaya reservoir and receive universal donor expanded TGF-beta-imprinted NK cells (TGFBi NK cells) intratumorally via Ommaya reservoir in 4-week cycles. Infusions via Ommaya will occur once weekly for three weeks followed by one week of rest. If patients have stable or improved disease, patients may continue to receive therapy for a total of 12 cycles. Participants will be followed for 5 years after completion of treatment, or until removal from study or death, whichever comes first.

Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Brain Tumors

A Phase I Study of Intra-Tumoral Injections of Ex Vivo Expanded Natural Killer Cells in Children and Young Adults With Recurrent or Progressive Supratentorial Malignant Brain Tumors

Individual participant data after de-identification.

Adverse events and clinically significant laboratory abnormalities (meeting grade 3, 4, or 5 criteria according to NCI CTCAE) will be summarized by maximum intensity and relationship to study drug(s). Grade 1 and 2 adverse events will be summarized if related to study therapy. Descriptive statistics will be utilized to display the data on toxicity seen. Toxicities will be summarized by tabulation in terms of type, grade and attribution for each dose level of each group of patients studied at the end of the trial.

RP2D is defined as the dose level at which fewer than one-third of participants experience a dose limiting toxicity (DLT)

Spots Global Cancer Trial Database for pediatric supratentorial neoplasm