Neural Stem Cell Therapy (NSC-CRAd-S-pk7) for the Treatment of Patients with Recurrent High-Grade Gliomas

Inclusion Criteria

• Patient must be age >= 18 years
• Patient has a Karnofsky performance status of >= 70%
• Patient has a life expectancy of >= 3 months
• When determining the maximum tolerated number of treatment cycles (MTC): patient has a histologically-confirmed diagnosis of a grade 3 or 4 glioma (eg., glioblastoma, grade 4 astrocytoma, grade 3 astrocytoma, grade 3 oligodendroglioma)
• 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 tumor resection
• No anticipated connection between the post-surgical cavity and the ventricular system, per the neurosurgeon’s judgement
• Absolute neutrophil count (ANC) of >= 1000 cells/mm^3
• Platelet count >= 100,000 cells/mm^3. If the patient’s platelet count is < 100,000 cells/mm^3 at the time of surgery, a platelet transfusion can be given per the discretion of the neurosurgeon
• 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 MTC has been identified, enrollment of 12-18 participants treated at the MTC will be limited to GBM patients at first or second recurrence
• All significant toxicities from previous anticancer therapy must have stabilized to a new baseline or resolved
• 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 is receiving radiation, chemotherapy, or another investigational agent
• Patient has had prior therapy with neural stem cells
• 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