Actively Recruiting
Autologous CD19-CD20-NKG2D-nsBicephali CAR-T for Relapsed/Refractory Central Nervous System Lymphoma
Led by Beijing Boren Hospital · Updated on 2026-05-04
30
Participants Needed
1
Research Sites
191 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Autologous CD19-CD20-NKG2D-nsBicephali CAR-T for Relapsed/Refractory Central Nervous System Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 to 75 years, male or female.
- Good performance status with ECOG 0-2 or Karnofsky Performance Status 70 or higher.
- Diagnosis of relapsed or refractory primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL).
- For PCNSL: prior treatment with at least 2 lines and not eligible for autologous stem cell transplant; or prior treatment with at least 3 lines; or disease progression or relapse within 12 months after autologous transplant. Must have received at least 1 line of high-dose methotrexate-based CNS therapy with documented progression, relapse, or intolerance.
- For SCNSL: relapse or refractory disease after at least 1 line of CNS lymphoma-directed therapy; if systemic lymphoma is present, it must have relapsed after treatment including anti-CD20 antibody and an anthracycline.
- Presence of measurable CNS disease with at least one lesion 1 cm or larger on contrast MRI, or positive cerebrospinal fluid by flow cytometry or cytology.
- Positive expression of CD19 and/or CD20 in tumor biopsy tissue or malignant cerebrospinal fluid cells. Prior failure of single-target CD19 or CD20 therapy allowed if last treatment was at least 6 months ago.
- Estimated life expectancy of 12 weeks or more.
- Adequate organ function including bone marrow, immune, liver, kidney, and heart function as specified.
- Required washout periods from prior treatments including chemotherapy, intrathecal therapy, corticosteroids, and short-acting cytotoxic drugs.
- Negative pregnancy test for women of childbearing potential and agreement to use contraception during treatment and for 24 months after infusion.
- Voluntary participation with signed informed consent.
You will not qualify if you...
- High-risk central nervous system status including brain herniation risk, severe cerebral edema, or uncontrolled seizures within 14 days.
- Prior severe toxicity from CAR-T or similar therapies including grade IV CRS or ICANS, or grade III without full recovery.
- Uncontrolled serious infections requiring intravenous treatment.
- Active hepatitis B or C infection, positive HIV antibody, or positive syphilis screening with high titer.
- Unresolved toxicity from prior cancer treatment worse than grade 2 except hair loss or fatigue.
- Severe cardiovascular or respiratory disease including recent heart attack, unstable angina, severe arrhythmia, pulmonary hypertension, or need for ventilatory support.
- History of other active cancers except cured carcinoma in situ or basal cell skin cancer.
- History of major organ transplantation.
- Active or untreated latent tuberculosis.
- Receipt of live vaccine within 6 weeks before lymphodepleting conditioning.
- Pregnancy or breastfeeding.
- Severe allergy to lymphodepleting drugs or CAR-T product components.
- Severe psychiatric illness or conditions making participation unsuitable in the investigator's judgment.
AI-Screening
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Trial Site Locations
Total: 1 location
1
Beijing GoBroad Boren Hospital
Beijing, Fengtai District, China, 100070
Actively Recruiting
Research Team
Y
Yajing Zhang
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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