NCT02192359

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

Active, enrolled Phase 1 Results posted Last updated 14 November 2025

What this trial tests

Phase 1 trial testing Carboxylesterase-expressing Allogeneic Neural Stem Cells in Recurrent Anaplastic Astrocytoma in 18 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

7 March 2016

Primary endpoint
21 February 2022

25 September 2026

Quick facts

Lead sponsor	City of Hope Medical Center
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	7 March 2016
Primary completion	21 February 2022
Estimated completion	25 September 2026
Sites	1 location across United States

Drugs / interventions tested

• Carboxylesterase-expressing Allogeneic Neural Stem Cells — full drug profile →
• Irinotecan (irinotecan) — full drug profile →
• Irinotecan Hydrochloride (Irinotecan Hydrochloride) — full drug profile →
• Laboratory Biomarker Analysis
• Pharmacological Study — full drug profile →

Conditions studied

• Recurrent Anaplastic Astrocytoma — all drugs for Recurrent Anaplastic Astrocytoma →
• Recurrent Anaplastic Oligoastrocytoma — all drugs for Recurrent Anaplastic Oligoastrocytoma →
• Recurrent Anaplastic Oligodendroglioma — all drugs for Recurrent Anaplastic Oligodendroglioma →
• Recurrent Glioblastoma — all drugs for Recurrent Glioblastoma →

Sponsor

City of Hope Medical Center

Who can join

Adults 18 to 69, any sex, with Recurrent Anaplastic Astrocytoma or Recurrent Anaplastic Oligoastrocytoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing a Dose-limiting Toxicity (DLT) Primary · 28 days post first dose of NSC treatment on day 1, cycle 1

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

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	1

Number of Participants With Grade 3 or Higher Toxicity Profile Attributed to NSCs Primary · Followed 30 days post treatment for all toxicities (min=33,max 142 days), up to 5 years for gene therapy toxicities

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.

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	0

Number of Participants With Grade 3 or Higher Toxicity Profile Attributed to Irinotecan Primary · Followed 30 days post treatment for all toxicities (min=33,max 142 days), up to 5 years for gene therapy toxicities

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.

Fatigue

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	1
Dose Level 4: 1.5x10^8 (2 Doses)	0
Dose Level 1: 5x10^7 (1 Dose)	4
Dose Level 2: 5x10^7 (2 Doses)	3
Dose Level 3: 1x10^8 (2 Doses)	3
Dose Level 4: 1.5x10^8 (2 Doses)	7

Platelet count decreased

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	1
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	0
Dose Level 1: 5x10^7 (1 Dose)	3
Dose Level 2: 5x10^7 (2 Doses)	3
Dose Level 3: 1x10^8 (2 Doses)	4
Dose Level 4: 1.5x10^8 (2 Doses)	7

White blood cell decreased

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	1
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	0
Dose Level 1: 5x10^7 (1 Dose)	3
Dose Level 2: 5x10^7 (2 Doses)	3
Dose Level 3: 1x10^8 (2 Doses)	4
Dose Level 4: 1.5x10^8 (2 Doses)	7

Meningitis

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	1
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	0
Dose Level 1: 5x10^7 (1 Dose)	4
Dose Level 2: 5x10^7 (2 Doses)	2
Dose Level 3: 1x10^8 (2 Doses)	4
Dose Level 4: 1.5x10^8 (2 Doses)	7

Hypophosphatemia

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	1
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	0
Dose Level 1: 5x10^7 (1 Dose)	4
Dose Level 2: 5x10^7 (2 Doses)	2
Dose Level 3: 1x10^8 (2 Doses)	4
Dose Level 4: 1.5x10^8 (2 Doses)	7

Brain abscess

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	1
Dose Level 4: 1.5x10^8 (2 Doses)	0
Dose Level 1: 5x10^7 (1 Dose)	4
Dose Level 2: 5x10^7 (2 Doses)	3
Dose Level 3: 1x10^8 (2 Doses)	3
Dose Level 4: 1.5x10^8 (2 Doses)	7

Catheter related infection

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	0
Dose Level 3: 1x10^8 (2 Doses)	0
Dose Level 4: 1.5x10^8 (2 Doses)	1
Dose Level 1: 5x10^7 (1 Dose)	4
Dose Level 2: 5x10^7 (2 Doses)	3
Dose Level 3: 1x10^8 (2 Doses)	4
Dose Level 4: 1.5x10^8 (2 Doses)	6

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

Pharmacokinetic data from patients who undergo intracerebral microdialysis will be summarized using descriptive statistics. hCE1m6-NSC dose and liposomal SN-38 concentrations in brain interstitium using microdialysis data from the patients treated with the initial neural stem cells (NSC) doses and from the patients in the cohort treated with the highest NSC dose. Ratios are reported as ratio x 100.

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	4.8	3.8 – 5.5
Dose Level 2: 5x10^7 (2 Doses)	0.8	0.3 – 1.7
Dose Level 4: 1.5x10^8 (2 Doses)	2.35	1.2 – 3.8

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

Pharmacokinetic data from patients who undergo intracerebral microdialysis will be summarized using descriptive statistics. hCE1m6-NSC dose and liposomal SN-38 concentrations in brain interstitium using microdialysis data from the patients treated with the initial neural stem cells (NSC) doses and from the patients in the cohort treated with the highest NSC dose. Ratio is reported as ratio x 100

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	6.9	6.0 – 9.3
Dose Level 2: 5x10^7 (2 Doses)	8.8	4.9 – 28.2
Dose Level 4: 1.5x10^8 (2 Doses)	12.2	3.7 – 26.3

Number of Participants With Clinical Benefit Defined by Response Assessment in Neuro-Oncology (RANO) Secondary · Until death or disease progression, a median of 2 months, up to 6 months

Clinical benefit is defined by participants achieving stable disease (SD), partial response (PR), or complete response (CR). CR: Complete disappearance of all enhancing disease (measurable and nonmeasureable) that is sustained for at least 4 weeks, stable or improved non-enhancing FLAIR/T2 lesions, no new lesions, off corticosteroids (physiologic replacement doses allowed), and neurologically stable or improved. PR: ≥ 50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing FLAIR/T2 lesions, n

Group	Value	95% CI
Dose Level 1: 5x10^7 (1 Dose)	0
Dose Level 2: 5x10^7 (2 Doses)	1
Dose Level 3: 1x10^8 (2 Doses)	1
Dose Level 4: 1.5x10^8 (2 Doses)	3

Adverse events — posted to ClinicalTrials.gov

Time frame: Followed 30 days post treatment for all toxicities (min=33,max 142 days) up to 5 years for gene therapy toxicities. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1: 5x10^7 (1 Dose)

Serious: 0/4 (0%)

Deaths: 4/4

Dose Level 2: 5x10^7 (2 Doses)

Serious: 1/3 (33%)

Deaths: 3/3

Dose Level 3: 1x10^8 (2 Doses)

Serious: 2/4 (50%)

Deaths: 4/4

Dose Level 4: 1.5x10^8 (2 Doses)

Serious: 5/7 (71%)

Deaths: 6/7

Serious adverse events (10 terms)

Reaction	System	Dose Level 1: 5x10^7 (1 Do…	Dose Level 2: 5x10^7 (2 Do…	Dose Level 3: 1x10^8 (2 Do…	Dose Level 4: 1.5x10^8 (2 …
Catheter related infection	Infections and infestations	—	—	—	—
Brain abscess	Infections and infestations	—	—	—	—
Meningitis	Infections and infestations	—	—	—	—
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Cerebrospinal fluid leakage	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Intracranial hemorrhage	Nervous system disorders	—	—	—	—
Altered mental status	Nervous system disorders	—	—	—	—
Confusion	Psychiatric disorders	—	—	—	—
Hematoma	Vascular disorders	—	—	—	—

Other adverse events (128 terms — click to expand)

Reaction	System	Dose Level 1: 5x10^7 (1 Do…	Dose Level 2: 5x10^7 (2 Do…	Dose Level 3: 1x10^8 (2 Do…	Dose Level 4: 1.5x10^8 (2 …
Headache	Nervous system disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Sinus bradycardia	Cardiac disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Gait disturbance	General disorders	—	—	—	—
Pain	General disorders	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—
Facial pain	General disorders	—	—	—	—
Irritability	General disorders	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—
Dysphasia	Nervous system disorders	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—
Confusion	Psychiatric disorders	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Fever	General disorders	—	—	—	—
Edema limbs	General disorders	—	—	—	—
Bruising	Injury, poisoning and procedural complications	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
Weight loss	Investigations	—	—	—	—
White blood cell decreased	Investigations	—	—	—	—
Hypermagnesemia	Metabolism and nutrition disorders	—	—	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—	—	—	—
Muscle weakness left-sided	Musculoskeletal and connective tissue disorders	—	—	—	—
Cerebrospinal fluid leakage	Nervous system disorders	—	—	—	—
Depressed level of consciousness	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Catheter related infection, Brain abscess, Meningitis, Myelodysplastic syndrome, Cerebrospinal fluid leakage, Headache, Intracranial hemorrhage, Altered mental status.

Data from ClinicalTrials.gov NCT02192359 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.
   Wu W, Klockow JL, Zhang M, Lafortune F, et al · · 2021 · cited 532× · PMID 34302977 · DOI 10.1016/j.phrs.2021.105780
2. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
   Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
3. Advances in local therapy for glioblastoma - taking the fight to the tumour.
   van Solinge TS, Nieland L, Chiocca EA, Broekman MLD. · · 2022 · cited 219× · PMID 35277681 · DOI 10.1038/s41582-022-00621-0
4. Progress and problems with the use of suicide genes for targeted cancer therapy.
   Karjoo Z, Chen X, Hatefi A. · · 2016 · cited 132× · PMID 26004498 · DOI 10.1016/j.addr.2015.05.009
5. The adaptive transition of glioblastoma stem cells and its implications on treatments.
   Wang Z, Zhang H, Xu S, Liu Z, et al · · 2021 · cited 101× · PMID 33753720 · DOI 10.1038/s41392-021-00491-w
6. Therapeutic Plasticity of Neural Stem Cells.
   Ottoboni L, von Wunster B, Martino G. · · 2020 · cited 69× · PMID 32265815 · DOI 10.3389/fneur.2020.00148
7. Inflammatory Mediators in Glioma Microenvironment Play a Dual Role in Gliomagenesis and Mesenchymal Stem Cell Homing: Implication for Cellular Therapy.
   Al-Kharboosh R, ReFaey K, Lara-Velazquez M, Grewal SS, et al · · 2020 · cited 60× · PMID 32793872 · DOI 10.1016/j.mayocpiqo.2020.04.006
8. Neural stem cell therapy for cancer.
   Bagó JR, Sheets KT, Hingtgen SD. · · 2016 · cited 56× · PMID 26314280 · DOI 10.1016/j.ymeth.2015.08.013