CAR-T cell therapy for severe systemic lupus erythematosus

Clinical Study of the Safety and Efficacy of CD19/BCMA CAR-T Cell Therapy for Refractory/Moderate-to-severe Systemic Lupus Erythematosus

This study is testing a new CAR-T cell therapy to see if it can help people with severe lupus who haven't found relief from other treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (other)
• Drugs / interventions: CAR-T, prednisone, chimeric antigen receptor, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Wuhan)
• Trial ID: NCT06349343 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of CD19/BCMA CAR-T cell therapy in patients with refractory or moderate-to-severe systemic lupus erythematosus (SLE). The trial aims to address the challenges faced by patients who have not responded to existing treatments, which often lead to ongoing disease activity and adverse effects from long-term glucocorticoid use. Participants will receive intravenous infusions of CAR-T cells and will be monitored for safety, tolerability, and preliminary efficacy over a follow-up period of up to one year. The study is designed to provide insights into the pharmacokinetics and pharmacodynamics of this innovative therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a diagnosis of refractory or moderate-to-severe systemic lupus erythematosus who have not responded to standard treatments.

Not a fit: Patients with mild SLE or those who have not undergone prior standardized treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a new, effective treatment option for patients suffering from refractory systemic lupus erythematosus.

How similar studies have performed: Preliminary studies have shown promise for CAR-T cell therapy in treating systemic lupus erythematosus, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Participants or their legal guardians understand and voluntarily sign the informed consent form, and be able to complete all the documents, procedures, follow-up examinations and treatments specified in the study protocol, with good compliance;
2. Age range from 18 to 70 years old, regardless of gender;
3. Participants diagnosed with SLE according to the 2019 European League Against Rheumatism (EULAR)/the American College of Rheumatology (ACR) SLE criteria at least 24 weeks prior to screening;
4. Refractory/moderate-to-severe SLE needs to meet the following criteria at screening: SELENA-SLEDAI score \> 6 points; PGA ≥ 1 points; BILAG-2004 organ system scores of at least 1 A or 2 B;Have received at least 12 weeks of standardized treatment for SLE prior to screening but lack efficacy;
5. Participants with fertility agree to take effective contraceptive measures throughout the study and within 3 months after the last follow-up visit.

Exclusion Criteria:

1. Diagnosis of active severe lupus nephritis within 8 weeks prior to screening, requiring medications prohibited by the research protocol for active nephritis, hemodialysis or prednisone ≥ 100 mg/d, or equivalent glucocorticoid therapy for ≥14 days;
2. Any attempted suicide or suicidal ideation within the past year prior to screening;
3. Presence of SLE or non-SLE related central nervous system diseases or pathological changes within 8 weeks prior to screening;
4. Previous or current diagnosis of non-SLE-related inflammatory arthropathy or skin diseases;
5. History of vital organ transplantation or hematopoietic stem cell/or bone marrow transplantation;
6. History of lymphoproliferative diseases;
7. Subjects with malignancy within 5 years prior to screening;
8. Have received plasma exchange, plasma separation, hemodialysis, or intravenous immunoglobulin (IVIG) within 14 days prior to screening;
9. Other autoimmune diseases requiring systemic therapy;
10. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the lower limit of research institution's test range. Subjects with positive hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, or syphilis;
11. Active or latent tuberculosis at screening;
12. Abnormalities in major organ function at screening;
13. Previous or current diagnosis of acute or chronic illnesses unrelated to SLE with obviously unstable or uncontrollable clinical symptoms;
14. Severe lupus lung damage at screening;
15. Severe lupus cardiac damage at screening;
16. Presence of uncontrollable infections at screening, requiring antibiotic therapy;
17. Have received live/attenuated vaccination within 4 weeks prior to screening or plan to receive live/attenuated vaccination throughout the study;
18. Have received intra-articular, intramuscular or intravenous glucocorticoids within 4 weeks prior to screening;
19. Have received any commercially available Janus kinase (JAK) inhibitor or Bruton tyrosine kinase (BTK) inhibitor within 12 weeks prior to screening;
20. Have received B-cell targeted therapy prior to screening;
21. Have received a biologic agent other than B-cell targeted therapy within 5 half-lives prior to screening;
22. Previously received therapies with CAR-T cells or other genetically modified T cells;
23. Have received therapeutic dose of corticosteroids within 7 days prior to leukapheresis or within 72 hours prior to infusion;
24. Subjects that have donated blood for ≥ 400mL or had a significant blood loss equivalent to at least 400mL within 4 weeks prior to screening, or have received blood transfusion within 8 weeks, or plan to donate blood during the study period;
25. History of ≥grade 2 bleeding within 4 weeks prior to screening or need for long-term continuous anticoagulant therapy;
26. Subjects that have undergone any major surgeries within 12 weeks prior to screening, or those who are scheduled to undergo major surgery during the study period;
27. History of drug abuse within 12 weeks prior to screening;
28. Female subjects who are pregnant or lactating, or intend to conceive within 2 years after the cell infusion; male patients whose female partners intend to conceive within 2 years after the cell infusion;
29. History of any significant drug allergy or intolerance;
30. Subjects that have participated in other clinical trials within 3 months prior to screening and/or currently participated in other clinical trials (those who do not receive study drugs are excluded);
31. Presence of other circumstances that make the subjects not eligible for participation in the study, in the opinion of the researchers.

Where this trial is running

Wuhan

• Union Hospital Tongji Medical College HUAZHONG University of Science and Technology — Wuhan, China (RECRUITING)

Study contacts

• Principal investigator: Qiubai Li, Professor — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: Qiubai Li, Professor

Conditions: Systemic Lupus Erythematosus, Refractory/Moderate-to-severe systemic lupus erythematosus, CAR-T cell therapy, CD19, BCMA