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

Sponsor
Zhejiang University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05030779
Collaborator
Yake Biotechnology Ltd. (Industry)
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Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Biological: Assigned Interventions CD19/BCMA CAR T-cells
Early Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
9 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Clinical Trial for the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Systemic Lupus Erythematosus
Anticipated Study Start Date :
Sep 10, 2021
Anticipated Primary Completion Date :
Mar 10, 2022
Anticipated Study Completion Date :
Sep 10, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  1. Autoantibody detection [Up to 90 days after CD19/BCMA CAR T-cells infusion]

    Detect the lupus erythematosus antibody titer in vivo

  2. Concentration of CAR-T cells [From admission to the end of the follow-up, up to 2 years]

    In peripheral blood and bone marrow

  3. Objective Response Rate, ORR [In 3 months of CD19/BCMA CAR-T cell infusion]

    Proportion of subjects with complete or partial remission

  4. 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.

  5. 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

  6. 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

  7. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 The First Affiliated Hospital,College of Medicine, Zhejiang University Hangzhou Zhejiang China 310003

Sponsors and Collaborators

  • Zhejiang University
  • Yake Biotechnology Ltd.

Investigators

  • Principal Investigator: He Huang, PhD, First Affiliated Hospital of Zhejiang University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
He Huang, Clinical Professor, Zhejiang University
ClinicalTrials.gov Identifier:
NCT05030779
Other Study ID Numbers:
  • CD19/BCMA-001
First Posted:
Sep 1, 2021
Last Update Posted:
Sep 1, 2021
Last Verified:
Aug 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by He Huang, Clinical Professor, Zhejiang University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 1, 2021