Intracerebroventricular Administration of CD19-CAR T Cells (CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/Mem T-lymphocytes) for the Treatment of Central Nervous System Lymphoma

NCT05625594 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 22240NCI-2022-09152P30CA033572R01CA266611
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will be assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0, particularly dose-limiting toxicities (DLTs), cytokine release syndrome (CRS) based on the revised CRS grading system by American Society for Transplantation and Cellular Therapy Consensus Criteria, and all other toxicities. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for participants experiencing DLTs, each type of cytopenia, disease response and progression free survival (PFS) at 6 months. All toxicities and side effects will be summarized in tables by period, organ, severity and attribution.

  Up to 15 years

• Disease response

  Will be assessed per International Primary Central Nervous System Lymphoma Collaborative Group criteria.

  Up to 15 years

Secondary Outcomes (6)

• Chimeric antigen receptor (CAR) T and endogenous T cell levels and phenotype

  Through 1 year post T cell infusion

• Cytokine levels

  Up to 15 years

• B cell level

  Through 1 year post T cell infusion

• Anemia, neutropenia, thrombocytopenia, and hypogammaglobulinemia lasting longer than 60 days or deemed medically significant

  Up to 15 years

• PFS time

  At 6 months

Study Arms (1)

Treatment (leukapheresis, CD19-CAR T cells)

EXPERIMENTAL

Patients may undergo catheterization, undergo leukapheresis, may receive fludarabine IV and cyclophosphamide IV, and receive CD19-CAR T cells ICV on study. Patients also undergo MRI, PET, CT, collection of blood samples, and CSF aspiration throughout the trial, and lumbar puncture as clinically indicated.

Procedure: Aspiration; Procedure: Biospecimen Collection; Procedure: Catheterization; Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Interventions

Aspiration PROCEDURE

Undergo CSF aspiration

Treatment (leukapheresis, CD19-CAR T cells)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (leukapheresis, CD19-CAR T cells)

Catheterization PROCEDURE

Undergo catheterization

Also known as: Catheter Insertion

Treatment (leukapheresis, CD19-CAR T cells)

CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes BIOLOGICAL

Given ICV

Also known as: CD19-CAR-specific/truncated EGFR Lentiviral Vector-transduced T Cells, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ TCM, CD19R(EQ)28zeta/truncated Human EGFR+ Central Memory T Cells, CD19R:CD28:lentiviral/EGFRt+ T Cells

Treatment (leukapheresis, CD19-CAR T cells)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (leukapheresis, CD19-CAR T cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (leukapheresis, CD19-CAR T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (leukapheresis, CD19-CAR T cells)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (leukapheresis, CD19-CAR T cells)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (leukapheresis, CD19-CAR T cells)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (leukapheresis, CD19-CAR T cells)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (leukapheresis, CD19-CAR T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have the ability to understand and the willingness to sign a written informed consent
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant can proceed with lymphodepletion (if applicable) and CAR T cell infusion only after the translated full consent form is signed
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable exceptions may be granted with study principal investigator (PI) approval
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Documented primary CNS lymphoma. Progression must be determined radiographically. Participant must have measurable disease which could be a measurable lymphomatous mass or, in the case of leptomeningeal only disease, measurable lymphoma cells in CSF by flow cytometry
• Patients with secondary CNS lymphoma with CNS only relapse, confirmed by PET-CT, may also be eligible, per PI discretion.
• Documented current CD19+ tumor expression if prior CD19 directed therapy was used
• Participant must have received and failed or have been intolerant to CNS directed therapy like high dose methotrexate or high dose cytarabine based regimens. Participants are not required to have failed all of these agents if, in the investigator's opinion, they would benefit from treatment on the current protocol
• Prior CAR T cell therapy is allowed if at least 3 months have elapsed prior to leukapheresis procedure
• If participant received prior CD19-CAR T cells persistence must be evaluated and found to be \<5% prior to leukapheresis procedure
• No known contraindications to leukapheresis, steroids or tocilizumab
• Participant of reproductive potential must agree to use acceptable birth control methods throughout study therapy and for 3 months after final dose of study treatment
• Total serum bilirubin =\< 2.0 mg/dL (within 14 days of signing the screening and leukapheresis consent)
• Patients with Gilbert syndrome may be included if their total bilirubin is =\< 3.0 x upper limit of normal (ULN) and direct bilirubin =\< 1.5 x ULN

You may not qualify if:

• Participant has not yet recovered from toxicities of prior therapy
• Presence of systemic lymphoma
• Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening and leukapheresis consent
• Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
• Active autoimmune disease requiring systemic immunosuppressive therapy
• Needing dexamethasone more than 4mg/day (or equivalent) within 72 hours prior to leukapheresis or CAR T cell infusion
• History of allergic reactions attributed to compounds of similar chemical or biologic composition or other agents used in this study
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to signing the screening and leukapheresis consent
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent with no known active disease present for \>= 3 years, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
• Subjects who are hepatitis B core antibody positive (or have a known history of hepatitis B virus \[HBV\] infection) should be monitored quarterly with a quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring should last until 12 months after last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core antibody (Ab) positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment
• Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
• Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Catheterization; Cyclophosphamide; fludarabine; Leukapheresis; Spinal Puncture; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Biopsy; Diagnostic Techniques, Neurological; Punctures; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Tanya Siddiqi

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: November 23, 2022
• Study Start: June 29, 2023
• Primary Completion (Estimated): May 21, 2026
• Study Completion (Estimated): May 21, 2026
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

US (1)