Clinical Trial Finder

Inclusion Criteria:

• - Patient has a prior, histologically-confirmed, diagnosis of a grade III or IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma), 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) - Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide.

• - Patient has a Karnofsky performance status of >= 70% - Patient has a life expectancy of >= 3 months.

• - 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 weeks prior to registration.

• - PROTOCOL-SPECIFIC CRITERIA.

• - Patient must be in need of a craniotomy for tumor resection or a stereotactic brain biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy ± chemotherapy.

• - Patients who will undergo tumor resection must have residual enhancing tumor (i.e. a gross total resection is not anticipated) - 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 >= 1500 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.

• - There is no limit to the number of prior therapies.

• - Patient must be able to understand and be willing to sign a written informed consent document.

• - INCLUSION CRITERIA FOR MTD COHORT 2.

• - Patient has a prior, histopathologically-confirmed diagnosis of glioblastoma.

• - Patient has not received any therapy for recurrent disease.

• - INCLUSION CRITERIA FOR PROCEEDING TO TREATMENT WITH IRINOTECAN DURING CYCLE 1.

• - A patient's daily total dose of dexamethasone must be =< 16 mg by day 3.

Exclusion Criteria:

• - Patient is homozygous or heterozygous for the UDP glycosyltransferase 1 family, polypeptide A1*28 allele (UGT 1A1*28) allele and/or has Gilbert's disease.

• - Patient must not be taking any cytochrome P450 3A4 (CYP3A4) hepatic enzyme-inducing anticonvulsants (phenytoin, fosphenytoin [Cerebyx], carbamazepine, phenobarbital, primidone, oxcarbazepine) or other moderate to strong CYP3A4 inhibitors or inducers for at least 2 weeks prior to start of study treatment.

• - Patient has anti-human leukocyte antigen (HLA) antibodies specific for HLA antigens expressed by the F3.

CD.CE NSCs.

• - Patient has not recovered from any toxicity of prior therapies; an interval of 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, and at least 2 weeks from taking the last dose of a targeted agent and the start of study treatment, with the exception of bevacizumab, where a wash out period of at least 4 weeks is required before starting study treatment.

• - Patient is taking flucytosine.

• - Patient is unable to undergo a magnetic resonance imaging (MRI) - Patient has chronic or active viral infections of the central nervous system (CNS) or an uncontrolled illness.

• - Patient may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.

• - History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan.

• - Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is participating in this study.

• - A patient with another active malignancy is ineligible for this study.

- Non-compliance

PRIMARY OBJECTIVES:

• I. To define the recommend phase II doses of intracranially administered active modified human form of carboxylesterase (hCE1m6)- neuronal stem cells (NSCs) (carboxylesterase-expressing allogeneic neural stem cells) in combination with intravenous irinotecan (irinotecan hydrochloride).

• II. To determine the biologic activity of the hCE1m6-NSCs by comparing SN-38 concentrations in the brain after treatment with hCE1m6-NSCs and irinotecan compared to irinotecan alone.

SECONDARY OBJECTIVES:

• I. To investigate the relationship between hCE1m6-NSC dose and SN-38 concentrations in brain interstitium.

• II. To characterize the relationship between intracerebral and systemic concentrations of irinotecan and SN-38.

• III. To assess for possible development of NSC immunogenicity after first exposure and with repeat doses of NSCs.

• IV. To evaluate the intracerebral distribution of NSCs by using iron-labeling as a cellular tracker.

• V. To describe the clinical benefit (defined as stable disease, partial response, or complete response) in patients who receive treatment with repeat cycles of NSCs and irinotecan.

• VI. To determine, at time of autopsy, the fate of the NSCs.

OUTLINE: This is a dose-escalation study of carboxylesterase-expressing allogeneic neural stem cells. Patients receive carboxylesterase-expressing allogeneic neural stem cells via intracerebral catheter on day 1 of week 1; weeks 1 and 3, weeks 1, 2, and 3; or weeks 1, 2, 3, and 4. Patients also receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 3 of week 1; weeks 1 and 3, weeks 1, 2, and 3; or weeks 1, 2, 3, and 4. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 15 years.

Arms

Experimental: Treatment (neuronal stem cells, irinotecan hydrochloride)

Patients receive carboxylesterase-expressing allogeneic neural stem cells via intracerebral catheter on day 1 of week 1; weeks 1 and 3, weeks 1, 2, and 3; or weeks 1, 2, 3, and 4. Patients also receive irinotecan hydrochloride IV over 90 minutes on day 3 of week 1; weeks 1 and 3, weeks 1, 2, and 3; or weeks 1, 2, 3, and 4. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Interventions

Biological: - carboxylesterase-expressing allogeneic neural stem cells

Given via intracerebral catheter

Drug: - irinotecan hydrochloride

Given IV

Other: - laboratory biomarker analysis

Correlative studies