SELECT-SLE: Biomarker-Guided CAR-T Target Selection for Refractory Lupus
Recruiting · NCT07523542 · Interventional (participants receive a specific treatment) · Lead sponsor: Beijing Biotech
View the official record on ClinicalTrials.gov →Interventions studied
Autologous anti-CD19 CAR-T cells, intravenous single infusion at protocol-defined dose level (1 x 10^6 or 3 x 10^6 CAR-positive viable T cells/kg).CyclophosphamideFludarabine
What this trial is about
study evaluates a biomarker-guided strategy to assign adults with refractory SLE to autologous CAR-T therapy targeting either CD19 or BCMA. Participants undergo centralized screening immunophenotyping to determine whether their disease appears B-cell-dominant (CD19-preferred) or plasma-cell-dominant (BCMA-preferred), followed by leukapheresis, lymphodepletion, and a single CAR-T infusion. The main goals are to assess safety, determine a recommended Phase 2 dose within each arm, and estimate remission rates by Week 24.
Who can take part
Age range
18 Years to 70 Years
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
Inclusion criteria
- 1\. Age 18 to 70 years at consent. 2. Meets 2019 EULAR/ACR classification criteria for SLE, with total score \>= 10.
- \. Active refractory disease at screening, defined by SELENA-SLEDAI \>= 8, or at least one BILAG A domain, or at least two BILAG B domains, or active lupus nephritis with significant proteinuria and active urinary sediment.
- \. Inadequate response, intolerance, or contraindication to at least 2 prior standard systemic regimens, including at least 1 immunosuppressant or biologic used for SLE or lupus nephritis. 5. Demonstrable targetable biology and assignment to one protocol arm: CD19 arm for measurable CD19-positive B-cell / B-cell-dominant disease, or BCMA arm for BCMA-positive plasmablast / plasma-cell-dominant disease and/or persistent serologic activity after prior B-cell depletion. 6. If active lupus nephritis is present, biopsy-proven class III, IV, V, or mixed proliferative / membranous LN within the previous 24 months, or investigator confirmation that repeat biopsy is unsafe but the clinical picture strongly supports active LN. 7. Adequate organ function: hemoglobin \>= 8.5 g/dL, ANC \>= 1.0 x 10\^9/L, platelets \>= 50 x 10\^9/L, AST / ALT \<= 2.5 x ULN, creatinine clearance \>= 30 mL/min, bilirubin \<= 2.0 mg/dL unless otherwise explained, and LVEF \>= 50%.
- \. Adequate venous access and eligibility for leukapheresis. 9. Negative pregnancy test and agreement to use effective contraception for 12 months after infusion.
- \. Ability to discontinue prohibited SLE medications per washout rules and willingness to comply with inpatient observation and long-term follow-up. 11. Written informed consent.
Exclusion criteria
- 1\. Active uncontrolled infection, including active tuberculosis, hepatitis B or C with active replication, or HIV.
- \. Prior CAR-T therapy or prior CD19- or BCMA-directed cell therapy. 3. Severe active CNS lupus requiring urgent escalation of immunosuppression, uncontrolled seizure disorder, or stroke within 60 days before screening. 4. End-stage organ failure not expected to improve with immune reset, such as dialysis-dependent kidney failure, uncontrolled advanced heart failure, or ICU-level respiratory instability. 5. Active malignancy or history of malignancy within 5 years, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, or other low-risk malignancy in durable remission. 6. Pregnant or breastfeeding. 7. Allogeneic hematopoietic stem cell transplant or solid organ transplant history.
- \. Contraindication to fludarabine, cyclophosphamide, leukapheresis, or standard rescue medications for CRS / ICANS. 9. Live vaccine within 4 weeks before lymphodepletion. 10. Participation in another interventional clinical study within 3 months before enrollment.
- \. Uncontrolled psychiatric disease, active substance misuse, or social circumstances that would impair adherence.
- \. Any condition that, in the investigator's judgment, makes participation unsafe or confounds interpretation of the study endpoints.
Where it is running
1 location listed.
- Peking University Shenzhen Hospital - Shenzhen, Guangdong, China