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 participants with recurrent or progressive 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 participants with recurrent or progressive malignant brain tumors. EXPLORATORY OBJECTIVES: I. To determine the 6 months overall survival (OS), defined as the percentage of participants 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 malignant brain tumors. VII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks. VIII. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks. 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 over 5 minutes via Ommaya reservoir on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Participants also undergo magnetic resonance imaging (MRI) of the brain during screening and on study and collection of tumor-associated fluid via Ommaya reservoir on study. Participants may also undergo MRI of the spine and lumbar puncture as clinically indicated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
The TGFβi NK cell product will be manufactured in the Cell Therapy Laboratory at Nationwide Children's Hospital and given via infusion.
Undergo placement of Ommaya reservoir
Imaging procedure
Ancillary studies
University of Alabama Birmingham
Birmingham, Alabama, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
University of California, San Francisco
San Francisco, California, United States
Indiana University
Indianapolis, Indiana, United States
Johns Hopkins
Baltimore, Maryland, United States
Washington University in Saint Louis
St Louis, Missouri, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Seattle Children's
Seattle, Washington, United States
Proportion of participants with treatment-emergent adverse events
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.
Time frame: From initiation of study treatment until 30 days from the end of therapy, approximately 1 year
Recommended Phase II dose (RP2D)
RP2D is defined as the dose level at which fewer than one-third of participants experience a dose limiting toxicity (DLT)
Time frame: From initiation of study treatment until 30 days from the end of therapy, approximately 1 year
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