Carboxylesterase-Expressing Allogeneic Neural Stem Cells and Irinotecan Hydrochloride in Treating Patients With Recurrent High-Grade Gliomas
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|ClinicalTrials.gov Identifier: NCT02192359|
Recruitment Status : Recruiting
First Posted : July 16, 2014
Last Update Posted : November 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Anaplastic Astrocytoma Recurrent Anaplastic Oligoastrocytoma Recurrent Anaplastic Oligodendroglioma Recurrent Glioblastoma Recurrent Gliosarcoma Recurrent Malignant Glioma Recurrent WHO Grade III Glioma||Biological: Carboxylesterase-expressing Allogeneic Neural Stem Cells Drug: Irinotecan Drug: Irinotecan Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
I. To define the recommended phase II doses (RP2D) of intracranially administered carboxylesterase-expressing allogeneic neural stem cells (hCE1m6-NSCs) in combination with intravenous irinotecan in patients with recurrent high grade glioma.
I. To describe the relationship between hCE1m6-NSC dose and liposomal SN-38 (SN-38) concentrations in brain interstitium.
II. To characterize the relationship between intracerebral and systemic concentrations of irinotecan (irinotecan hydrochloride) and SN-38.
III. To investigate the biologic activity of hCE1m6 NSCs by comparing SN-38 concentrations in the brain after treatment with hCE1m6-NSCs and irinotecan versus irinotecan alone.
IV. To assess for possible development of adenovirally transduced neural stem cell (NSC) immunogenicity after first exposure and with repeat doses of NSCs.
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 intracranially over 1.5-4.5 hours on days 1 and 15 (day 1 only for patients at dose level 1) and irinotecan hydrochloride intravenously (IV) over 90 minutes on days 3 and 17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 3 and 6 months, and then annually thereafter for a minimum of 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Intracranially Administered Carboxylesterase-Expressing Neural Stem Cells in Combination With Intravenous Irinotecan in Patients With Recurrent High-Grade Gliomas|
|Actual Study Start Date :||March 7, 2016|
|Estimated Primary Completion Date :||March 7, 2020|
|Estimated Study Completion Date :||July 7, 2020|
Experimental: Treatment (hCE1m6-NSCs and irinotecan hydrochloride)
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 Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Incidence of dose limiting toxicities (DLTs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ]Tables will be created to summarize all toxicities and side effects by dose, course, organ severity (by NCI CTCAE version 4.0), and attribution. Rates and associated 95% Clopper Pearson confidence limits will be estimated for DLTs.
- Incidence of all attributable toxicities graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]Tables will be created to summarize all toxicities and side effects by dose, course, organ severity (by NCI CTCAE version 4.0), and attribution.
- Pharmacokinetics parameters, including maximum concentration and area under the curve of irinotecan and SN-38 in dialysate and plasma [ Time Frame: 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 ]Pharmacokinetic data from patients who undergo intracerebral microdialysis will be summarized using descriptive statistics and graphical methods. The biologic activity of the carboxylesterase-expressing allogeneic neural stem cells (hCE1m6-NSCs) will be assessed using a one-sided two-sample t test. Regression analysis will be used to assess the relationship between 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) dose and from the patients in the expansion cohort treated with the highest NSC dose.
- Development of neural stem cells (NSC) immunogenicity after first and repeat exposures [ Time Frame: Up to 15 years ]Will be summarized using descriptive statistics and graphical methods.
- Clinical benefit, defined by tumor response based on magnetic resonance imaging (MRI) results [ Time Frame: Up to 15 years ]Rates and associated 95% Clopper Pearson confidence limits will be estimated for clinical benefit at the recommended phase II dose.
- Fate of the neural stem cells (NSCs), defined by NSC persistence [ Time Frame: Up to 15 years ]Will be summarized using descriptive statistics and graphical methods.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02192359
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Jana L. Portnow 800-826-4673|
|Principal Investigator: Jana L. Portnow|
|Principal Investigator:||Jana L Portnow||City of Hope Medical Center|