Ignite Creation Date:
2025-12-25 @ 1:40 AM
Ignite Modification Date:
2026-01-07 @ 9:57 AM
Study NCT ID:
NCT05625594
Status:
RECRUITING
Last Update Posted:
2025-07-08
First Post:
2022-11-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Intracerebroventricular Administration of CD19-CAR T Cells (CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/Mem T-lymphocytes) for the Treatment of Central Nervous System Lymphoma
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
Official Title:
A Phase 1 Study to Evaluate Intracerebroventricular (ICV) Administration of CD19-Targeting Chimeric Antigen Receptor (CAR) T Cells in Patients With CNS Lymphoma
Status:
RECRUITING
Status Verified Date:
2025-07
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 tests the safety, side effects, and best dose of intracerebroventricularly (ICV) administered CD19-chimeric antigen receptor (CAR) T cells in treating patients with central nervous system (CNS) lymphoma. CAR T cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, CD19, on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. ICV is an injection technique that delivers the CD19-CAR T cells directly into the cerebrospinal fluid (which flows in and around the hollow spaces of the brain and spinal cord, and the thin layers of tissue that cover and protect the brain and spinal cord) in the brain, through a surgically placed catheter. Giving CD19-CAR T cells ICV may be more effective at treating patients with CNS lymphoma than giving them via other methods.
Detailed Description:
PRIMARY OBJECTIVES:
I. Examine and describe the safety and feasibility of ICV delivery of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes (CD19-CAR T cells) and determine the recommended phase 2 dose (RP2D) in participants with primary CNS lymphoma, or secondary lymphoma with CNS only relapse.
II. Determine the activity of ICV-delivered CD19-CAR T cells based on disease response at the maximum tolerated dose (MTD).
SECONDAY OBJECTIVES:
I. Describe persistence, expansion and phenotype of endogenous and CD19-CAR T cells in peripheral blood (PB), and cerebral spinal fluid (CSF), when available.
II. Describe cytokine levels (PB, CSF) over study period. III. Quantify B-cell aplasia over the treatment period as a surrogate for targeted cytotoxicity in the periphery.
IV. Assess prolonged cytopenia based on prolonged grade 4 continuous or intermittent anemia, neutropenia, thrombocytopenia, and hypogammaglobulinemia \> 60 days or deemed medically significant.
V. Estimate rates of disease response. VI Estimate rate of 6-month progression free survival (PFS6mon). VII. Estimate median overall survival (OS).
EXPLORATORY OBJECTIVES:
I. Characterize changes in potential molecular and gene-analysis based indicators of neurotoxicity in CSF and PB.
II. Describe the tumor phenotype pre- and post-therapy. III. Characterize functional and phenotypic metabolic profile of CAR T cells pre- and post-infusion.
IV. Assess the presence and magnitude of human anti-mouse antibody (HAMA).
OUTLINE: This is a dose-escalation study followed by a dose-expansion study.
Patients may undergo catheterization, undergo leukapheresis, may receive fludarabine intravenously (IV) and cyclophosphamide IV, and receive CD19-CAR T cells ICV on study. Patients also undergo magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), collection of blood samples, and CSF aspiration throughout the trial, and lumbar puncture as clinically indicated.
I. Examine and describe the safety and feasibility of ICV delivery of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes (CD19-CAR T cells) and determine the recommended phase 2 dose (RP2D) in participants with primary CNS lymphoma, or secondary lymphoma with CNS only relapse.
II. Determine the activity of ICV-delivered CD19-CAR T cells based on disease response at the maximum tolerated dose (MTD).
SECONDAY OBJECTIVES:
I. Describe persistence, expansion and phenotype of endogenous and CD19-CAR T cells in peripheral blood (PB), and cerebral spinal fluid (CSF), when available.
II. Describe cytokine levels (PB, CSF) over study period. III. Quantify B-cell aplasia over the treatment period as a surrogate for targeted cytotoxicity in the periphery.
IV. Assess prolonged cytopenia based on prolonged grade 4 continuous or intermittent anemia, neutropenia, thrombocytopenia, and hypogammaglobulinemia \> 60 days or deemed medically significant.
V. Estimate rates of disease response. VI Estimate rate of 6-month progression free survival (PFS6mon). VII. Estimate median overall survival (OS).
EXPLORATORY OBJECTIVES:
I. Characterize changes in potential molecular and gene-analysis based indicators of neurotoxicity in CSF and PB.
II. Describe the tumor phenotype pre- and post-therapy. III. Characterize functional and phenotypic metabolic profile of CAR T cells pre- and post-infusion.
IV. Assess the presence and magnitude of human anti-mouse antibody (HAMA).
OUTLINE: This is a dose-escalation study followed by a dose-expansion study.
Patients may undergo catheterization, undergo leukapheresis, may receive fludarabine intravenously (IV) and cyclophosphamide IV, and receive CD19-CAR T cells ICV on study. Patients also undergo magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), collection of blood samples, and CSF aspiration throughout the trial, and lumbar puncture as clinically indicated.
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-09152 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 22240 | OTHER | City of Hope Medical Center | View | |
| P30CA033572 | NIH | None | https://reporter.nih.gov/quic… | View |
| R01CA266611 | NIH | None | https://reporter.nih.gov/quic… | View |