A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Systemic Lupus Erythematosus

Early Phase 1

• Conditions: Systemic Lupus Erythematosus; Autoimmune Diseases
• Interventions: Biological: Assigned Interventions CD19/BCMA CAR T-cells

• Registration Number: NCT05030779
• Lead Sponsor: Zhejiang University

Brief Summary

A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Systemic Lupus Erythematosus

Detailed Description

Autoimmune diseases only show local pathological damage, but more often systemic lesions. If not diagnosed and treated in time or poorly controlled, a risk of disability or even death as the course of the disease progresses. Studies have shown that B cells can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or they can differentiate into plasma cells to release autoantibodies, and play an important role in the occurrence and progression of autoimmune diseases. In recent years, it has become a major research focus to deplete B cells in patients or inhibit B cell function. This research focuses on CAR-T cells killing B cells. In 2019, Kansal and others released their team's in vivo experiments to prove that CD19 CAR-T cells have achieved significant and long-lasting effects in the treatment of systemic lupus erythematosus. This fully reflects the application prospects of CAR-T cells in autoimmune diseases.

Based on the current research progress, our center intends to conduct research on the safety and effectiveness of CD19/BCMA CAR-T cells in the treatment of refractory systemic lupus erythematosus.

Study Timeline

• Status Verified: 2021-08
• Study First Submitted: 2021-08-18
• Study First Submitted QC: 2021-08-31
• Last Update Submitted: 2021-08-31
• Study First Posted: 2021-09-01
• Last Update Posted: 2021-09-01
• Study Start: 2021-09-10
• Primary Completion: 2022-03-10
• Study Completion: 2022-09-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. Systemic lupus erythematosus with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment
2. Estimated survival time> 12 weeks;
3. Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up;
4. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria

• Subjects with any of the following exclusion criteria were not eligible for this trial:

  1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
  2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
  3. Pregnant (or lactating) women;
  4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
  5. Active infection of hepatitis B virus or hepatitis C virus;
  6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
  7. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
  8. Other uncontrolled diseases that were not suitable for this trial;
  9. Patients with HIV infection;
  10. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study
  11. Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L
  12. Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment of SLE	Assigned Interventions CD19/BCMA CAR T-cells	Experimental：Administration of CD19/BCMA CAR T-cells A dose levels of 1-4\*10E6/kg are administrated for each subject.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	Baseline up to 28 days after CD19/BCMA CAR T-cells infusion	Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)	Up to 90 days after CD19/BCMA CAR T-cells infusion	Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

Secondary Outcome Measures

Name	Time	Method
Autoantibody detection	Up to 90 days after CD19/BCMA CAR T-cells infusion	Detect the lupus erythematosus antibody titer in vivo
Concentration of CAR-T cells	From admission to the end of the follow-up, up to 2 years	In peripheral blood and bone marrow
Objective Response Rate, ORR	In 3 months of CD19/BCMA CAR-T cell infusion	Proportion of subjects with complete or partial remission
Disease control rate, DCR	From Day 28 CD19/BCMA CAR-T infusion up to 2 years	The percentage of patients with remission and stable disease after treatment in the total evaluable cases.
Duration of remission, DOR	24 months post CD19/BCMA CAR-T cells infusion	The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause
Progression-free survival, PFS	24 months post CD19/BCMA CAR-Tcells infusion	The time from cell reinfusion to the first assessment of disease progression or death from any cause
Overall survival, OS	From CD19/BCMA CAR-T infusion to death，up to 2 years	The time from the cell reinfusion to death due to any cause

Trial Locations

Locations (1)

The First Affiliated Hospital,College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China