Ignite Creation Date:
2025-12-24 @ 3:16 PM
Ignite Modification Date:
2025-12-26 @ 9:59 AM
Study NCT ID:
NCT04214392
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-06
First Post:
2019-12-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Chimeric Antigen Receptor (CAR) T Cells With a Chlorotoxin Tumor-Targeting Domain for the Treatment of MMP2+ Recurrent or Progressive Glioblastoma
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
Official Title:
A Phase 1 Study to Evaluate Chimeric Antigen Receptor (CAR) T Cells With a Chlorotoxin Tumor-Targeting Domain for Patients With MMP2+ Recurrent or Progressive Glioblastoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain in treating patients with MPP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.
Detailed Description:
PRIMARY OBJECTIVES:
I. Assess the feasibility and safety of dual delivery of chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes NCI SYs (chlorotoxin \[CLTX\]-CAR T cells) for participants with MMP2+ recurrent or progressive glioblastoma.
II. Determine the maximum tolerated dose schedule (MTD) and a recommended phase 2 dosing plan (RP2D) for dual delivery of CLTX-CAR T cells for participants with MMP2+ recurrent or progressive glioblastoma.
SECONDARY OBJECTIVES:
I. Describe persistence, expansion, and phenotype of endogenous and CLTX-CAR CAR T cells in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF).
II. Describe cytokine levels in PB, TCF, and CSF over the study period.
III. In research participants who receive the full schedule of 3 cycles of CLTX-CAR T cells:
IIIa. Estimate the six month progression free survival (PFS) rate. IIIb. Estimate the nine month overall survival (OS) rate. IIIc. Estimate disease response rates. IIId. Estimate median overall survival (OS).
IV. In study participants who undergo an additional biopsy/resection or autopsy:
IVa. Evaluate CAR T cell persistence in the tumor tissue and the location of the CAR T cells with respect to the injection site.
IVb. Evaluate CLTX-targeted antigen expression levels on tumor tissue pre and post CAR T cell therapy.
V. Use mathematical modeling of tumor growth to evaluate benefit of treatment.
OUTLINE: This is a dose-escalation study.
Patients receive chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes NCI SYs via dual delivery starting on day 0 for 3 weekly cycles over 28 days. Each treatment cycle begins with one or two CAR T cell infusions (one at each catheter site) and lasts for 1 week. Beginning 1 week after cycle 3, patients may continue with CAR T treatment per principal investigator and patient discretion. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 3, 6, 9, and 12 months, and then yearly for up to 15 years.
I. Assess the feasibility and safety of dual delivery of chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes NCI SYs (chlorotoxin \[CLTX\]-CAR T cells) for participants with MMP2+ recurrent or progressive glioblastoma.
II. Determine the maximum tolerated dose schedule (MTD) and a recommended phase 2 dosing plan (RP2D) for dual delivery of CLTX-CAR T cells for participants with MMP2+ recurrent or progressive glioblastoma.
SECONDARY OBJECTIVES:
I. Describe persistence, expansion, and phenotype of endogenous and CLTX-CAR CAR T cells in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF).
II. Describe cytokine levels in PB, TCF, and CSF over the study period.
III. In research participants who receive the full schedule of 3 cycles of CLTX-CAR T cells:
IIIa. Estimate the six month progression free survival (PFS) rate. IIIb. Estimate the nine month overall survival (OS) rate. IIIc. Estimate disease response rates. IIId. Estimate median overall survival (OS).
IV. In study participants who undergo an additional biopsy/resection or autopsy:
IVa. Evaluate CAR T cell persistence in the tumor tissue and the location of the CAR T cells with respect to the injection site.
IVb. Evaluate CLTX-targeted antigen expression levels on tumor tissue pre and post CAR T cell therapy.
V. Use mathematical modeling of tumor growth to evaluate benefit of treatment.
OUTLINE: This is a dose-escalation study.
Patients receive chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes NCI SYs via dual delivery starting on day 0 for 3 weekly cycles over 28 days. Each treatment cycle begins with one or two CAR T cell infusions (one at each catheter site) and lasts for 1 week. Beginning 1 week after cycle 3, patients may continue with CAR T treatment per principal investigator and patient discretion. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 3, 6, 9, and 12 months, and then yearly for up to 15 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: