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

Clinical Trial for the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Systemic Lupus Erythematosus

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

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital,College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

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

Description

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 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: Treatment of SLE; Experimental：Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject.	Biological: Assigned Interventions CD19/BCMA CAR T-cells; Drug: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Name: CD19/BCMA CAR T-cells injection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 10, 2021
• Primary Completion (Anticipated): March 10, 2022
• Study Completion (Anticipated): September 10, 2022

Study Registration Dates

• First Submitted: August 18, 2021
• First Submitted That Met QC Criteria: August 31, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; CD19 CAR T-cell therapy; BCMA CAR T-cell therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Autoimmune Diseases
• Other Study ID Numbers: CD19/BCMA-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No