Personalized CAR-T cells targeting CD19 and CD20 for relapsed or refractory central nervous system lymphoma
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
This trial will try personalized CAR-T cells that target CD19 and CD20 to help adults whose primary or secondary CNS lymphoma has relapsed or not responded to prior treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Boren Hospital Academic / other |
| Drugs / interventions | CAR-T, chemotherapy, immunotherapy, fludarabine, methotrexate |
| Locations | 1 site (Beijing, Fengtai District) |
| Trial ID | NCT07555561 on ClinicalTrials.gov |
What this trial studies
This is a single-center, open-label Phase 1 trial testing autologous CD19-CD20-NKG2D-nsBicephali CAR-T cells in adults with relapsed or refractory primary or secondary CNS lymphoma. The study uses a 3+3 dose-escalation design with two planned dose levels (1×10^6 and 2×10^6 CAR-positive T cells/kg), followed by a dose-expansion stage once a safe dose is identified. Participants undergo leukapheresis to manufacture CAR-T cells, receive a single CAR-T infusion, and are monitored closely for safety, pharmacokinetics, and anti-tumor activity. Safety and efficacy follow-up continues for 24 months after infusion, with optional long-term safety follow-up up to 15 years.
Who should consider this trial
Good fit: Adults 18–75 years old with measurable relapsed or refractory primary or secondary CNS lymphoma, adequate performance status (ECOG 0–2 or KPS ≥70), and prior CNS-directed therapy as specified are the intended candidates.
Not a fit: Patients with poor performance status (ECOG >2), no measurable CNS disease, uncontrolled systemic illness, or who do not meet prior-treatment requirements are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this dual-target CAR-T approach could produce deeper and more durable remissions by reducing tumor escape from single-antigen loss and improving control of CNS disease.
How similar studies have performed: Single-target CD19 CAR-T therapies have shown responses in some CNS lymphoma cases but are limited by antigen loss and variable durability, and multi-target CAR-T approaches like this remain largely novel and unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Beijing, Fengtai District
- Beijing GoBroad Boren Hospital — Beijing, Fengtai District, China (Recruiting)
Study contacts
- Study coordinator: Yajing Zhang
- Email: yajing_cart66@126.com
- Phone: +86 18501333856
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.