Autologous CD19-CD20-NKG2D-nsBicephali CAR-T for Relapsed/Refractory Central Nervous System Lymphoma

June 1, 2026 updated by: Beijing Boren Hospital

An Exploratory Clinical Study to Evaluate the Safety and Efficacy of Autologous CD19-CD20-NKG2D-nsBicephali CAR-T for Relapsed/Refractory Central Nervous System Lymphoma

Central nervous system lymphoma (CNSL) includes primary CNS lymphoma (PCNSL) and secondary CNS lymphoma (SCNSL), with diffuse large B-cell lymphoma as the predominant pathological type. Disease progression is often rapid and the relapse rate is high. Current standard treatment is centered on CNS-directed regimens based on high-dose methotrexate (HD-MTX), but salvage options for relapsed or refractory disease remain limited. In addition, the blood-brain barrier restricts effective exposure of many drugs within the central nervous system, making deep remission and durable disease control difficult to achieve. This study evaluates autologous CD19-CD20-NKG2D-nsBicephali CAR-T in patients with relapsed or refractory PCNSL or SCNSL. By engineering the patient's T cells into effector cells capable of recognizing both CD19 and CD20, this approach is intended to address tumor antigen heterogeneity and reduce immune escape associated with downregulation or loss of a single target. CAR-T cells may also migrate into cerebrospinal fluid and brain parenchyma, expand within the CNS compartment, and directly eliminate CD19/CD20-positive lymphoma cells. The study is designed to systematically evaluate the safety and preliminary efficacy of this investigational CAR-T therapy in relapsed or refractory CNSL.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single-center, open-label exploratory clinical study to evaluate the safety, tolerability, and efficacy of autologous CD19-CD20-NKG2D-nsBicephali CAR-T in relapsed/refractory central nervous system lymphoma. The study has two stages. The first stage is a dose-escalation stage with two planned dose groups: a low-dose group of 1×10^6 CAR-positive T cells/kg and a high-dose group of 2×10^6 CAR-positive T cells/kg. A 3+3 design will be used for dose escalation. After enrollment and completion of the DLT observation period in each dose group, available safety and pharmacokinetic data will be reviewed to determine subsequent enrollment and treatment decisions, including whether additional dose groups should be added. The second stage is a dose-expansion stage. Once a given dose group is confirmed to be safe, that dose group and any lower confirmed dose groups may be expanded concurrently. Participants will be followed for safety and efficacy for 24 months after cell infusion. After completion of the main study, participants will be re-consented for long-term safety follow-up until 15 years after cell infusion.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Fengtai District
      • Beijing, Fengtai District, China, 100070
        • Beijing GoBroad Boren Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-75 years, male or female.
  • Good performance status: ECOG 0-2 or Karnofsky Performance Status (KPS) ≥70.

  • Diagnosis of relapsed/refractory primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL).

    • PCNSL: prior treatment with at least 2 lines and unsuitable for autologous hematopoietic stem cell transplantation; or prior treatment with at least 3 lines; or disease progression/relapse within 12 months after autologous transplantation. Participants must previously have received at least 1 line of HD-MTX-based CNS-directed therapy (intravenous dose ≥2500 mg/m²) and have documented progression, relapse, or intolerance.
    • SCNSL: relapse or refractory disease after at least 1 line of CNSL-directed therapy; if systemic lymphoma is also present, the systemic component must have relapsed after treatment including an anti-CD20 monoclonal antibody and an anthracycline.
  • Presence of measurable CNS disease (at least one enhancing lesion ≥1 cm on contrast-enhanced brain MRI, or positive CSF by flow cytometry and/or cytology).
  • Positive expression of CD19 and/or CD20 in tumor biopsy tissue or malignant CSF cells. Participants with prior failure of single-target CD19- or CD20-directed therapy are allowed, provided the washout period since the last treatment is at least 6 months.
  • Estimated life expectancy ≥12 weeks.

  • Adequate organ function:

    • Bone marrow and immune function: peripheral blood absolute CD3 count ≥50/mm³ and absolute lymphocyte count ≥0.2×10^9/L; ANC ≥1000/μL; platelets ≥50,000/μL, without recent red blood cell or platelet transfusion.
    • Hepatic and renal function: creatinine clearance (Cockcroft-Gault) ≥45 mL/min; if relaxed to 30-45 mL/min, fludarabine dose must be reduced strictly; AST and ALT ≤3×ULN; total bilirubin and alkaline phosphatase ≤1.5×ULN.
    • Cardiopulmonary function: LVEF ≥50% (NYHA class I-II); oxygen saturation on room air >92%.
  • Prior-treatment washout: anti-B-cell chemotherapy/immunotherapy stopped for at least 3 weeks; intrathecal CNS therapy stopped for at least 1 week; systemic corticosteroids (except physiologic replacement) stopped for at least 1 week; short-acting cytotoxic drugs stopped for at least 3 days.
  • Negative pregnancy test for women of childbearing potential; participants with partners of childbearing potential must agree to use effective contraception during treatment and for 24 months after infusion.
  • Voluntary participation and signed informed consent.

Exclusion Criteria:

  • High-risk CNS status: imaging showing high-risk brain herniation or uncontrollable intracranial pressure elevation risk (large subcortical mass effect with significant cerebral edema), or severe status epilepticus or poorly controlled seizures within 14 days.
  • Prior severe CAR-T toxicity: prior CD19/CD20-targeted therapy (including CAR-T or bispecific antibodies) with grade IV CRS or ICANS, or grade III CRS/ICANS without full recovery after treatment.
  • Uncontrolled serious active infection requiring systemic intravenous therapy.
  • Positive virology: active hepatitis B (HBsAg positive and peripheral blood HBV DNA ≥10^3 copies/mL); hepatitis C (HCV RNA positive); positive syphilis screening with titer ≥1:8; HIV antibody positive.
  • Toxicity from prior antitumor therapy not recovered to CTCAE v5.0 grade ≤2, except alopecia or fatigue.
  • Severe cardiovascular or respiratory disease, including myocardial infarction, unstable angina, or severe arrhythmia within the past 6 months; moderate-to-severe pulmonary arterial hypertension; or need for ventilatory support or oxygen reservoir mask assistance.
  • Prior history of, or concurrent, other active malignancy, except cured carcinoma in situ or basal cell skin cancer.
  • History of major solid organ transplantation.
  • Active tuberculosis at screening, or latent tuberculosis without systematic prophylaxis.
  • Live vaccine received within 6 weeks before lymphodepleting conditioning.
  • Pregnancy or breastfeeding; severe allergy to any lymphodepleting drug or any component of the CAR-T product.
  • Severe psychiatric disease, major depression, suicidal tendency, or any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental - Low-dose autologous CD19-CD20-NKG2D-nsBicephali CAR-T
a low-dose group of 1×10^6 CAR-positive T cells/kg
Biological: Autologous CD19-CD20-NKG2D-nsBicephali CAR-T Cell Injection
Autologous CD19-CD20-NKG2D-nsBicephali CAR-T is an autologous cell product derived from the participant's own cells. Peripheral blood mononuclear cells are collected by leukapheresis, T cells are isolated, and viral transduction is used ex vivo to generate autologous CAR-T cells for reinfusion. The product name stated in the protocol is Autologous CD19-CD20-NKG2D-nsBicephali CAR-T Cell Injection. Package specification is approximately 10-40 mL per dose. Transport condition is 2-8°C. Storage condition is sealed, protected from light, and maintained in liquid nitrogen conditions.
Experimental: Experimental - High-dose autologous CD19-CD20-NKG2D-nsBicephali CAR-T
a high-dose group of 2×10^6 CAR-positive T cells/kg
Biological: Autologous CD19-CD20-NKG2D-nsBicephali CAR-T Cell Injection
Autologous CD19-CD20-NKG2D-nsBicephali CAR-T is an autologous cell product derived from the participant's own cells. Peripheral blood mononuclear cells are collected by leukapheresis, T cells are isolated, and viral transduction is used ex vivo to generate autologous CAR-T cells for reinfusion. The product name stated in the protocol is Autologous CD19-CD20-NKG2D-nsBicephali CAR-T Cell Injection. Package specification is approximately 10-40 mL per dose. Transport condition is 2-8°C. Storage condition is sealed, protected from light, and maintained in liquid nitrogen conditions.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Proportion of participants with dose-limiting toxicity (DLT) within 28 days after infusion; determination of MTD or RP2D.
Time Frame: Within 28 days after infusion.
Within 28 days after infusion.
Grade and frequency of adverse events (AEs), serious adverse events (SAEs), laboratory abnormalities, and adverse events of special interest (AESIs, including CRS and ICANS).
Time Frame: From signing of informed consent through 24 months after infusion or the end-of-study visit, whichever occurs first.
From signing of informed consent through 24 months after infusion or the end-of-study visit, whichever occurs first.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Proportion of participants achieving objective response
Time Frame: at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24.
at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24.
Proportion of participants achieving complete response (CR)
Time Frame: Month 3 (3 months ±14 days)
Month 3 (3 months ±14 days)
Response categories (CR/CRu/PR/SD/PD)
Time Frame: Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24
Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24
Best overall response (BOR)
Time Frame: From Day 0 (CAR-T infusion) until disease progression, initiation of new anti-tumor therapy, death, or Month 24 after infusion, whichever occurs first; response is assessed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24.
From Day 0 (CAR-T infusion) until disease progression, initiation of new anti-tumor therapy, death, or Month 24 after infusion, whichever occurs first; response is assessed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24.
Time to response (TTR)
Time Frame: From Day 0 to the first documented PR or CR/CRu, assessed through Month 24 after infusion; tumor assessments are performed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24.
From Day 0 to the first documented PR or CR/CRu, assessed through Month 24 after infusion; tumor assessments are performed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24.
Duration of response (DOR)
Time Frame: From the date of first documented CR/CRu/PR until first documented PD or death, whichever occurs first, assessed through Month 24 after infusion.
From the date of first documented CR/CRu/PR until first documented PD or death, whichever occurs first, assessed through Month 24 after infusion.
Progression-free survival (PFS)
Time Frame: From Day 0 until first documented disease progression or death, whichever occurs first, assessed through Month 24 after infusion.
From Day 0 until first documented disease progression or death, whichever occurs first, assessed through Month 24 after infusion.
Overall survival (OS)
Time Frame: From Day 0 until death from any cause, assessed through Month 24 after infusion.
From Day 0 until death from any cause, assessed through Month 24 after infusion.
In baseline CSF-positive participants only: CSF conversion to negative, CSF MRD conversion to negative if MRD is performed, and duration of CSF MRD negativity
Time Frame: Assessed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24 after infusion; duration of CSF MRD negativity is assessed through Month 24.
Assessed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24 after infusion; duration of CSF MRD negativity is assessed through Month 24.
CNS response components
Time Frame: Assessed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24 after infusion.
Assessed at Day 28 and Months 2, 3, 4, 5, 6, 9, 12, 15, 18, and 24 after infusion.
Cmax
Time Frame: Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
Tmax
Time Frame: Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
AUC0h-28d
Time Frame: Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
AUC0-last
Time Frame: Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
PD parameters, including changes in peripheral blood CD19-CD20-NKG2D-positive cells and serum cytokines such as TNF-alpha and IFN-gamma before and after infusion
Time Frame: Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.
Assessed from Day 0 through Month 24 after infusion on Days 0, 1, 3, 5, 7, 9, 11, 14, 21, and 28; Months 2, 3, 6, 9, 12, 15, 18, and 24; and through study completion or early withdrawal, up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Boren Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BJBR-2026-LBL-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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