CD19/BCMA CAR-T Cell Therapy for Refractory/Moderate-to-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

The purpose of the study is to explore the safety and efficacy of cluster of differentiation 19 (CD19)/B cell maturation antigen (BCMA) CAR-T cell therapy in refractory/moderate-to-severe systemic lupus erythematosus(SLE).

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: CD19/BCMA CAR-T cell therapy

Detailed Description

The prognosis of patients with refractory/moderate-to-severe systemic lupus erythematosus (SLE) remains poor, due to two major therapeutic obstacles: (1) current treatment strategies including glucocorticoids, immunosuppressive agents, biological agents, are still difficult to achieve disease control, making the disease condition of some patients continue to be active or even worse; (2) some patients are unable to wean themselves off glucocorticoid and face the risk of numerous adverse effects caused by long-term glucocorticoid dependence, such as glucocorticoid-related diabetes, femoral head necrosis, hypertension, stress ulcers, and infection, etc. Therefore, there is a strong unmet clinical need for more effective treatment for patients suffering from refractory/moderate-to-severe SLE. Several preclinical and clinical studies have shown the efficacy of chimeric antigen receptor T (CAR-T) cell therapy in SLE. The aim of this study is to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of cluster of differentiation 19 (CD19)/B cell maturation antigen (BCMA) CAR-T cell therapy in refractory/moderate-to-severe SLE. Patients with refractory/moderate-to-severe SLE will be invited to participate in the study, to receive CD19/BCMA CAR-T cell intravenous infusion and follow-up visits of up to 1 years after enrollment. Given that the pretreatment chemotherapy (fludarabine,cyclophosphamide) of CAR-T therapy in current SLE clinical studies is mostly based on experiences in hematologic malignancies, which may cause severe complications such as infection, there is a lack of evidence-based rationale for patients with SLE to receive pretreatment chemotherapy. This study will explore the feasibility of CAR-T cell therapy without pretreatment chemotherapy in the treatment of refractory/moderate-to-severe systemic lupus erythematosus.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li, professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn

Study Locations

• China
  • Wuhan, China
    • Recruiting
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Contact: Qiubai Li, PhD; Email: qiubaili@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CD19/BCMA CAR-T cell therapy intervention; The first 3 participants will be enrolled to receive CAR-T cell infusion without pretreatment chemotherapy. Then participants' peripheral blood samples would be collected for CAR-T cell testing. If test results showed the presence of CAR-T cells on certain time points, CAR-T cell therapy without pretreatment chemotherapy is considered feasible, and the subsequent 17 participants will receive the consistent regimen; Otherwise, the 3 participants will be re-treated with pretreatment chemotherapy and CAR-T cell infusion, and the subsequent 17 participants will receive pretreatment chemotherapy-containing regimen.

Biological: CD19/BCMA CAR-T cell therapy; CD19/BCMA CAR-T cell will be infused intravenously at 3 doses: Dose A, Dose B, Dose C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Safety and tolerability will be assessed by incidence and severity of adverse events (AEs) and serious AEs (SAEs). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded by ASTCT criteria, other AEs are assessed by CTCAE V5.0 criteria	Within 1 years after CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with SRI-4 response	SRI-4 response is defined as: 1) the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score decrease by no less than 4 points from baseline; 2) the British Isles Lupus Assessment Group (BILAG) score with no new A domain score and no more than 1 new B domain score compared to baseline; 3) the Physician Global Assessment (PGA) score increase less than 0.3 point from baseline.	Within 1 years after CAR-T cell infusion(month 1, month 3, month 6, month 9, month 12）
Changes in the Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score from baseline	Range [0, 105]，higher score represents worse disease activity	Within 1 years after CAR-T cell infusion(month 1, month 3, month 6, month 9, month 12）
Changes in the BILAG-2004 score from baseline	Range [0, 72]，higher score represents worse disease activity	Within 1 years after CAR-T cell infusion(month 1, month 3, month 6, month 9, month 12）
Changes in the Physician Global Assessment (PGA) score from baseline	Range [0, 3]，higher score represents worse disease activity	Within 1 years after CAR-T cell infusion(month 1, month 3, month 6, month 9, month 12）
Pharmacokinetics (PK)	Concentration of CAR-T cell in peripheral blood will be evaluated	Within 1 years after CAR-T cell infusion(per 3 days in month 1, per month in month 2 - month 12）
Pharmacodynamics (PD)	Pharmacodynamics (PD) will be assessed by levels of cytokines(IL-2、IL-6、IL-10、IFN-γ), changes of lymphocyte subsets, immunological indexes(IgG、IgM、IgA、IgE) in peripheral blood	Within 1 years after CAR-T cell infusion(per 3 days in month 1, per month in month 2 - month 12）

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Principal Investigator: Qiubai Li, Professor, Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: March 31, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T cell therapy; CD19; BCMA; Refractory/Moderate-to-severe systemic lupus erythematosus
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: UHCT230949

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No