AzTrials
AzTrials

Central Nervous System LymphomaPhase 1NCT05625594

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

A Phase 1 study testing Aspiration, Biospecimen Collection and Catheterization in people with Central Nervous System Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Central Nervous System Lymphoma
What is being tested?
Aspiration, Biospecimen Collection and Catheterization
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
29 Jun 2023to 22 May 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 30Show fewer
  • 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
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (within 14 days of signing the screening and leukapheresis consent)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (within 14 days of signing the screening and leukapheresis consent)
  • Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula (within 14 days of signing the screening and leukapheresis consent)
  • Cardiac function (12 lead-electrocardiogram [ECG]) without acute abnormalities requiring investigation or intervention (within 14 days of signing the screening and leukapheresis consent)
  • Absolute neutrophil count >= 750/uL (within 14 days of signing the screening and leukapheresis consent)
  • Hemoglobin (Hb) >= 8 g/dl (within 14 days of signing the screening and leukapheresis consent)
  • Platelet count >= 50,000/uL (within 14 days of signing the screening and leukapheresis consent)
  • Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) > 40% (evaluation within 6 weeks of screening does not need to be repeated) (within 14 days of signing the screening and leukapheresis consent)
  • Oxygen (O2) saturation > 92% not requiring oxygen supplementation (within 14 days of signing the screening and leukapheresis consent)
  • Seronegative for HIV qPCR, HCV*, active HBV (Surface Antigen Negative), and syphilis (RPR)
  • If positive, Hepatitis C RNA quantitation must be performed. OR
  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable.
  • Meets other institutional and federal requirements for infectious disease titer requirements Note Infectious disease testing to be performed within 28 days prior to enrollment.
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days of signing the screening and leukapheresis consent)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • Human immunodeficiency virus (HIV) infection
  • Active significant bacterial, fungal or viral (other than those listed) infections
  • Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Tanya Siddiqi, 626-803-3458, tsiddiqi@coh.org

    Tanya Siddiqi

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. Estimate rates of disease response. VI Estimate rate of 6-month progression free survival (PFS6mon). VII. Estimate median overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. 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.

Being tested
Aspiration, Biospecimen Collection, Catheterization, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes, Computed Tomography

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AspirationProcedure or surgery

    Undergo CSF aspiration

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • CatheterizationProcedure or surgery

    Also called Catheter Insertion

    Undergo catheterization

  • CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytesBiological

    Also called 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

    Given ICV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

    Undergo PET

Study groups in NCT05625594
Study groupRoleWhat they receive
Treatment (leukapheresis, CD19-CAR T cells)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 15 years

  2. Disease response

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

    Measured: Up to 15 years

Secondary outcomes (6)

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

    Detected in peripheral blood (PB) and cerebral spinal fluid (CSF) when available, (absolute number per uL by flow). CAR T cell level and cytokines will be interrogated if CRS or neurotoxicity attributed at the probable level to CAR T cells are observed. Statistical and graphical longitudinal methods will be used to describe the profile of the CAR T cells, and endogenous immune cell populations including B cells through one-year post T cell infusion. Regression analysis will be used to assess the relationship between CAR T cell levels and B cells levels.

    Measured: Through 1 year post T cell infusion

  2. Cytokine levels

    Measured in PB, and CSF, when available. CAR T cell level and cytokines will be interrogated if CRS or neurotoxicity attributed at the probable level to CAR T cells are observed. Cytokine levels (PB and CSF) will be described using longitudinal statistical and graphical methods over the study period.

    Measured: Up to 15 years

  3. B cell level

    Measured in PB. CAR T cell level and cytokines will be interrogated if CRS or neurotoxicity attributed at the probable level to CAR T cells are observed. Statistical and graphical longitudinal methods will be used to describe the profile of the CAR T cells, and endogenous immune cell populations including B cells through one-year post T cell infusion. Regression analysis will be used to assess the relationship between CAR T cell levels and B cells levels.

    Measured: Through 1 year post T cell infusion

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

    Measured in PB. Rates and associated 90% Clopper and Pearson Binomial confidence limits will be estimated for each type of cytopenia.

    Measured: Up to 15 years

  5. PFS time

    Patients are considered a failure for this endpoint if they die (regardless of cause) or experience disease relapse.

    Measured: At 6 months

  6. Overall survival (OS) time

    Kaplan Meier methods will be used to estimate median OS and graph the results.

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2022
  2. Study start29 Jun 2023
  3. Primary completion22 May 2028 (estimated)
  4. Study completion22 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05625594
Sponsor's protocol ID
22240
Other IDs
NCI-2022-09152, 22240, P30CA033572, R01CA266611
Status last verified
Jun 2026
First submitted
15 Nov 2022
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Aspiration, Biospecimen Collection and Catheterization in people with Central Nervous System Lymphoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 15 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05625594.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in