Multiple Doses of Neural Stem Cell Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas

This phase I trial studies the effect of multiple doses of NSC-CRAd-S-pk7 in treating patients with high-grade gliomas that have come back (recurrent). NSC-CRAd-S-pk7 consists of neural stem cells that carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.

PRIMARY OBJECTIVE:

I. Determine the recommended maximum tolerated number of cycles (MTC) of intracavitary (ICT) administered Neural Stem Cells-expressing CRAd-S-pk7 (NSCCRAd-S-pk7) for phase II testing based on dose-limiting toxicities (DLTs), the overall toxicity profile, and activity in patients with recurrent high-grade glioma (HGG).

SECONDARY OBJECTIVES:

I. Measure possible development of antibody and T cell responses to the neural stem cells (NSCs) and/or the oncolytic virus in cerebrospinal fluid (CSF), resection cavity fluid (when possible to obtain by aspiration before administering study agent through the ICT Rickham), and blood.

II. Evaluate the intracerebral biodistribution of NSC-CRAd-S-pk7 when permission to perform a brain autopsy on a study participant is given.

III. Identify the evidence of possible NSC migration outside of the brain, the presence of viral particles, and/or both in the CSF and blood.

IV. Estimate the rates of disease response using modified Response Assessment in Neuro-Oncology (RANO) criteria, progression-free survival at 6 months (PFS6months), overall survival at 9 months (OS9months), and median PFS and OS in the recurrent HGG patients, and estimate the rates of disease response, PFS6months, and OS9months for the cohort of 12 GBM patients at first or second recurrence who will be treated at the MTC.

V. Assess changes in HSPG and survivin expression in pre- and post-treatment tumor tissue samples treatment.

VI. Identify possible mechanisms of immune escape by analyzing immune cell population changes in the tumor microenvironment (TME) in pre- and post-treatment tumor tissue samples.

VII. Generate a biomathematical model to describe spatial temporal changes in tumor growth that may predict the effect of NSC-CRAd-S-pk7 on tumor response based on magnetic resonance imaging (MRI) measurements.

OUTLINE:

Patients undergo standard of care surgical resection. Patients then receive NSC-CRAd-S-pk7 intracerebrally over 10 minutes once weekly (QW) for up to 4 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 and 6 months, and then annually thereafter.

Eligibility Criteria:
Inclusion Criteria:

* Patient must be age \>= 18 years
* Patient has a Karnofsky performance status of \>= 70%
* Patient has a life expectancy of \>= 3 months
* Patient has histologically-confirmed, diagnosis of a grade III or IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified \[NOS\]), or has a prior, histologically-confirmed, diagnosis of a grade II glioma and now has radiographic findings consistent with a high-grade glioma (grade III or IV)
* Imaging studies show evidence of recurrent, supratentorial tumor(s). The presence of infratentorial tumor is allowed if the patient also has supratentorial disease that is amenable to placement of an intracavitary Rickham catheter
* Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
* The patient must be in need of surgery for tumor resection
* Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
* Absolute neutrophil count (ANC) of \>= 1000 cells/mm\^3
* Platelet count \>= 100,000 cells/mm\^3
* Total bilirubin =\< 2.0 mg/dl
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 4 times the institutional upper limit of normal
* Serum creatinine =\< the institutional upper limit of normal
* At least 6 weeks must have elapsed since taking a nitrosourea-containing chemotherapy regimen
* At least 4 weeks since completing a non-nitrosourea-containing cytotoxic chemotherapy regimen (except temozolomide: only an interval of 23 days is required from the last dose administered when patient has been recently treated with the standard temozolomide regimen of daily for 5 days, repeated every 28 days)
* At least 2 weeks from taking the last dose of a targeted agent
* At least 4 weeks from the last dose of bevacizumab
* There is no limit to the number of prior therapies for enrollment during treatment schedule escalation; however, once the maximum tolerated treatment schedule has been identified further enrollment to complete the accrual goal of 12 participants treated at the maximum tolerated treatment schedule will be limited to glioblastoma patients at first or second recurrence
* All participants must have the ability to understand and the willingness to sign a written informed consent
* The effects of this treatment on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients must agree to use an effective method of contraception while participating in this study. Women of childbearing potential must have a negative pregnancy test =\< 2 week prior to registration

Exclusion Criteria:

* Patient has anti-human leukocyte antigen (HLA) antibodies specific for HLA Class I antigens (A\*01, A\*31, B\*07, B\*15, C\*07) expressed by the neural stem cells
* Patient is receiving radiation, chemotherapy, or another investigational agent
* Patient has had prior therapy with neural stem cells
* Patient has not recovered from any toxicity (\> grade 1) of prior therapies, except alopecia
* Patient is unable to undergo a brain MRI
* Patient has chronic or active viral infections of the central nervous system (CNS)
* Patient has a coagulopathy or bleeding disorder
* Patient has an uncontrolled illness including ongoing or active infection
* Patient has another active malignancy
* Patient is pregnant or breastfeeding
* A patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol