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)
• As per protocol version 6, for treatment schedules 4 and 4a enrollment is now restricted to glioblastoma patients at first recurrence to ensure homogeneous patient populations for comparing these two treatment schedules
• Imaging studies show evidence of recurrent, supratentorial tumor(s)
• 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
• If the patient’s platelet count is < 100,000 cells/mm3 at the time of surgery, a platelet transfusion can be given per the discretion of the neurosurgeon
• 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, for treatment schedules 4 and 4a enrollment is now restricted to glioblastoma patients at first recurrence to ensure homogeneous patient populations for comparing these two treatment schedules
• 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, patients of childbearing potential and sexually-active patients must agree to use an effective method of contraception while participating in this study. Patients of childbearing potential must have a negative pregnancy test =< 2 week prior to registration

Exclusion Criteria

• Patient has multi-focal disease
• 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