Carboxylesterase-Expressing Allogeneic Neural Stem Cells and Irinotecan Hydrochloride in Treating Patients With Recurrent High-Grade Gliomas

This is an interventional treatment trial for Recurrent Anaplastic Astrocytoma Read More

Inclusion Criteria:

• Patient must be able to understand and be willing to sign a written informed consent document
• Participant must be willing to comply with study and/or follow-up procedures
• Karnofsky performance status >= 70%
• Life expectancy of >= 3 months
• 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 tumor(s); if a patient is going to be enrolled to dose level two or higher, the patient must have a component of supratentorial disease (so as to enable placement of a Rickham reservoir/catheter) that is amenable to resection or biopsy
• High-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
• Participant 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
• Based on the neurosurgeon?s judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
• Neurosurgeon finds the prospective participant is able to undergo neurosurgery
• Any number of prior therapies is permitted; from the start of study treatment, the following time periods must have elapsed: 6 weeks from nitrosourea-containing chemotherapy, 4 weeks from non-nitrosourea-containing cytotoxic chemotherapy (except 23 days from last daily dose of temozolomide taken in a 5 of 28 day regimen), and 2 weeks from last dose of a targeted agent (except 4 weeks for bevacizumab); there is no time period requirement for prior radiation therapy
• Any clinically significant toxicity from prior therapy must have improved to grade 0 or grade 1
• Absolute neutrophil count (ANC) >= 1,500 cells/ul
• Platelets > 100,000 cells/ul
• Total bilirubin =< 2.0 mg/dl
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 4 times institutional upper limit of normal
• Serum creatinine =< 1.5 x the institutional upper limit of normal
• Homozygous negative for the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT 1A1)*28 allele
• Absence anti-human leukocyte antigen (HLA) antibodies specific for HLA class I antigens expressed by the coagulation factor III (thromboplastin, tissue factor) (F3).cytosine deaminase (CD).carboxylesterase (CE) NSCs
• Negative serum pregnancy test (women of childbearing potential only)
• Agreement by females of childbearing potential and sexually active males 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

Exclusion Criteria:

• Prior therapy with neural stem cells
• Use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers including hepatic enzyme-inducing anticonvulsants (phenytoin, fosphenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) within 2 weeks prior to start of study treatment
• Use of moderate to strong CYP3A4 inhibitors within 2 weeks prior to start of study treatment
• Use of drugs known to inhibit UGT1A1, such as atazanir, gemfibrozil, indinavir, or ketoconazole, within 2 weeks prior to start of study treatment
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids, such as systemic cyclosporine and tacrolimus; consult principal investigator for questions, including necessary washout period for the specific drug
• Flucytosine within 2 weeks prior to start of study treatment
• Use of herbal medications
• Current use (or planned use during the treatment period) of other investigational agents, or biological, chemotherapy, radiation or other anti-tumor therapy
• Patient has known human immunodeficiency virus (HIV) or hepatitis C infection; baseline testing for HIV or hepatitis C is not required
• Prospective participant is unable to undergo a magnetic resonance imaging (MRI) with contrast agent
• Known chronic or active viral infections of the central nervous system (CNS)
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Diagnosis of Gilbert?s disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan
• Known sensitivity to any of the products to be administered during dosing
• Any other active malignancy
• Pregnant women and women who are lactating
• 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
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)