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

NCT02192359 | Active Not Recruiting Phase 1 Results DMC

• 4 other identifiers: 14108NCI-2014-01463P30CA033572R01CA198076
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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-grade gliomas that have come back. Placing genetically modified neural stem cells into brain tumor cells may make the tumor more sensitive to irinotecan hydrochloride. Irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboxylesterase-expressing allogeneic neural stem cells and irinotecan hydrochloride may be a better treatment for high-grade gliomas.

Conditions

Recurrent Anaplastic Astrocytoma; Recurrent Anaplastic Oligoastrocytoma; Recurrent Anaplastic Oligodendroglioma; Recurrent Glioblastoma; Recurrent Gliosarcoma; Recurrent Malignant Glioma; Recurrent WHO Grade III Glioma

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing a Dose-limiting Toxicity (DLT)

  Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT is defined as an adverse event that is related to the administration of NSCs and/or irinotecan, occurs during the first treatment cycle and meets any of the following: 1. Received less than 80% of study treatments except due to CNS toxicity 2. Grade 4 thrombocytopenia or anemia or neutropenia lasting \> 7 days 3. Febrile neutropenia with ANC \< 0.5 x10\^9/L 4. Grade 3 central nervous system (CNS) disorder lasting \> 7 days not attributed to tumor or surgery and not present at baseline 5. Second occurrence of grade 3 CNS disorder not attributed to tumor or surgery and not present at baseline 6. Any grade 4 CNS disorder not attributed to tumor or surgery and not present at baseline 7. Grade 3 toxicity despite therapy lasting \> 7 days 8. Grade 3 toxicity resulting in study agent discontinuation 9. Grade 4 toxicity, except grade 4 diarrhea responding to therapy within 3 days

  28 days post first dose of NSC treatment on day 1, cycle 1

• Number of Participants With Grade 3 or Higher Toxicity Profile Attributed to NSCs

  Grade 3 or higher toxicity profile as assessed by the NCI CTCAE version version 4.0. Toxicities reported are possibly, probably or definitely related to NSCs.

  Followed 30 days post treatment for all toxicities (min=33,max 142 days), up to 5 years for gene therapy toxicities

• Number of Participants With Grade 3 or Higher Toxicity Profile Attributed to Irinotecan

  Grade 3 or higher toxicity profile as assessed by the NCI CTCAE version version 4.0. Toxicities reported are possibly, probably or definitely related to Irinotecan.

  Followed 30 days post treatment for all toxicities (min=33,max 142 days), up to 5 years for gene therapy toxicities

Secondary Outcomes (3)

• Median Ratio of SN-38 Area Under the Curve (AUC) to CPT-11 AUC in Plasma

  Pre-dose, at 90 minutes (just prior to the end of the infusion), and then at 30 minutes, 1, 2, 4, 8, 24, and 48 hours after the end of the infusion after day 1, cycle 1

• Median Ratio of SN-38 AUC to CPT-11 AUC in the Brain

  Pre-dose, at 90 minutes (just prior to the end of the infusion), and then at 30 minutes, 1, 2, 4, 8, 24, and 48 hours after the end of the infusion after day 1, cycle 1

• Number of Participants With Clinical Benefit Defined by Response Assessment in Neuro-Oncology (RANO)

  Until death or disease progression, a median of 2 months, up to 6 months

Study Arms (1)

Treatment (hCE1m6-NSCs and irinotecan hydrochloride)

EXPERIMENTAL

Patients receive carboxylesterase-expressing allogeneic neural stem cells intracranially over 1.5-4.5 hours on days 1 and 15 (day 1 only for patients at dose level 1) and irinotecan hydrochloride IV over 90 minutes on days 3 and 17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Carboxylesterase-expressing Allogeneic Neural Stem Cells; Drug: Irinotecan; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Carboxylesterase-expressing Allogeneic Neural Stem Cells BIOLOGICAL

Given intracranially

Also known as: CE-secreting Allogeneic NSCs, hCE1m6-NSC

Treatment (hCE1m6-NSCs and irinotecan hydrochloride)

Irinotecan DRUG

Given IV

Treatment (hCE1m6-NSCs and irinotecan hydrochloride)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate

Treatment (hCE1m6-NSCs and irinotecan hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (hCE1m6-NSCs and irinotecan hydrochloride)

Pharmacological Study OTHER

Correlative studies

Treatment (hCE1m6-NSCs and irinotecan hydrochloride)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jana Portnow
• Organization: City of Hope Medical Center

JPortnow@coh.org

626-546-8293

Study Officials

• Jana L Portnow

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: July 16, 2014
• Study Start: March 7, 2016
• Primary Completion: February 21, 2022
• Study Completion (Estimated): September 25, 2026
• Last Updated: November 14, 2025
• Results First Posted: April 29, 2024

Record last verified: 2025-11

Locations

US (1)