Status:
ACTIVE_NOT_RECRUITING
Carboxylesterase-Expressing Allogeneic Neural Stem Cells and Irinotecan Hydrochloride in Treating Patients With Recurrent High-Grade Gliomas
Lead Sponsor:
City of Hope Medical Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Recurrent Anaplastic Astrocytoma
Recurrent Anaplastic Oligoastrocytoma
Eligibility:
All Genders
18-69 years
Phase:
PHASE1
Brief Summary
This phase I trial studies the side effects and best dose of carboxylesterase-expressing allogeneic neural stem cells when given together with irinotecan hydrochloride in treating patients with high-g...
Detailed Description
PRIMARY OBJECTIVE: I. To define the recommended phase II doses (RP2D) of intracranially administered carboxylesterase-expressing allogeneic neural stem cells (hCE1m6-NSCs) in combination with intrave...
Eligibility Criteria
Inclusion
- 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
- 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)
Key Trial Info
Start Date :
March 7 2016
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 25 2026
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT02192359
Start Date
March 7 2016
End Date
September 25 2026
Last Update
November 14 2025
Active Locations (1)
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1
City of Hope Medical Center
Duarte, California, United States, 91010