Actively Recruiting
Study of Intracerebroventricular CD19-CAR T Cell Therapy for Central Nervous System Lymphoma A Phase 1 Trial Evaluating Safety, Dosage, and Activity
Led by City of Hope Medical Center · Updated on 2025-07-08
20
Participants Needed
1
Research Sites
151 weeks
Total Duration
On this page
Sponsors
C
City of Hope Medical Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, side effects, and best dose of CD19-chimeric antigen receptor (CAR) T cells given directly into the brain's cerebrospinal fluid to treat patients with central nervous system (CNS) lymphoma. This phase I study focuses on patients with primary CNS lymphoma or secondary CNS lymphoma relapse. The CAR T cells are modified immune cells designed to target cancer cells expressing CD19, and delivering them intracerebroventricularly (ICV) may improve treatment effectiveness compared to other methods. Participants undergo a dose-escalation phase followed by a dose-expansion phase. Treatments include surgical catheter placement for ICV delivery of the CD19-CAR T cells, intravenous chemotherapy with fludarabine and cyclophosphamide, and leukapheresis to collect T cells for modification. Throughout the study, participants receive imaging scans such as MRI, PET, and CT, as well as blood and cerebrospinal fluid (CSF) collections, including lumbar punctures when clinically needed. During the trial, researchers monitor safety by tracking adverse events and disease response for up to 15 years. They also study CAR T cell behavior in blood and CSF, immune markers, and side effects like prolonged low blood counts. Participants' cardiac function, oxygen levels, and infection status are regularly checked. Overall survival and progression-free survival are assessed, along with exploratory analyses of neurotoxicity and tumor characteristics before and after therapy.
CONDITIONS
Official 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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Ability to understand and willing to sign informed consent
- Agreement to allow use of archival tissue from diagnostic tumor biopsies or approval by principal investigator
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Documented primary CNS lymphoma or secondary CNS lymphoma with CNS-only relapse confirmed by PET-CT
- Measurable disease by imaging or measurable lymphoma cells in cerebrospinal fluid by flow cytometry
- Documented current CD19+ tumor expression if prior CD19-directed therapy was used
- Prior CNS-directed therapy (e.g., high dose methotrexate or cytarabine) with failure or intolerance, or investigator's discretion for benefit
- Prior CAR T cell therapy allowed if at least 3 months before leukapheresis and persistence <5%
- No contraindications to leukapheresis, steroids, or tocilizumab
- Use of acceptable birth control methods during study and for 3 months after final dose if of reproductive potential
- Total serum bilirubin ≤ 2.0 mg/dL (or ≤ 3.0 x ULN with Gilbert syndrome) within 14 days before consent
- AST and ALT ≤ 2.5 x upper limit of normal within 14 days before consent
- Creatinine clearance ≥ 50 mL/min within 14 days before consent
- Cardiac function without acute abnormalities on ECG within 14 days before consent
- Absolute neutrophil count ≥ 750/uL within 14 days before consent
- Hemoglobin ≥ 8 g/dL within 14 days before consent
- Platelet count ≥ 50,000/uL within 14 days before consent
- Ejection fraction > 40% by echocardiogram or MUGA within 6 weeks of screening
- Oxygen saturation > 92% without oxygen supplementation within 14 days before consent
- Seronegative or undetectable viral load for HIV, HCV, active HBV, and syphilis per testing within 28 days before enrollment
- Negative pregnancy test for women of childbearing potential within 14 days before consent
You will not qualify if you...
- Not recovered from toxicities of prior therapy
- Presence of systemic lymphoma
- Clinically significant or unstable arrhythmias within two weeks before consent
- History of optic neuritis, other CNS immunologic or inflammatory diseases, or seizure disorder
- Active autoimmune disease requiring systemic immunosuppression
- Use of dexamethasone >4 mg/day within 72 hours before leukapheresis or CAR T infusion
- History of allergic reactions to similar compounds or study agents
- Known bleeding disorders such as von Willebrand's disease or hemophilia
- Stroke or intracranial hemorrhage within 6 months before consent
- History of other malignancies unless resected or treated with curative intent and no active disease for ≥3 years, except skin basal or localized squamous cell carcinoma
- Uncontrolled active infection
- Active hepatitis B or C infection by PCR or serology
- HIV infection
- Active significant bacterial, fungal, or viral infections other than listed
- Other conditions contraindicating participation due to safety concerns
- Potential inability to comply with study procedures due to feasibility or logistics issues
AI-Screening
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Trial Site Locations
Total: 1 location
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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