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A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Sjogren's Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05085431
Recruitment Status : Recruiting
First Posted : October 20, 2021
Last Update Posted : October 20, 2021
Sponsor:
Collaborator:
Yake Biotechnology Ltd.
Information provided by (Responsible Party):
He Huang, Zhejiang University

Tracking Information
First Submitted Date  ICMJE October 11, 2021
First Posted Date  ICMJE October 20, 2021
Last Update Posted Date October 20, 2021
Estimated Study Start Date  ICMJE November 5, 2021
Estimated Primary Completion Date November 5, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2021)
  • Dose-limiting toxicity (DLT) [ Time Frame: 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) [ Time Frame: Up to 90 days after CD19/BCMA CAR T-cells infusion ]
    Incidence of treatment-emergent adverse events [Safety and Tolerability]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2021)
  • Concentration of CAR-T cells [ Time Frame: From admission to the end of the follow-up, up to 2 years ]
    In peripheral blood and bone marrow
  • Objective Response Rate, ORR [ Time Frame: In 3 months of CD19/BCMA CAR-T cell infusion ]
    Proportion of subjects with complete or partial remission
  • Disease control rate, DCR [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From CD19/BCMA CAR-T infusion to death,up to 2 years ]
    The time from the cell reinfusion to death due to any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Sjogren's Syndrome
Official Title  ICMJE A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Sjogren's Syndrome
Brief Summary A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Sjogren's Syndrome
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. Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, frequently accompanied by systemic symptoms. The presence of various autoantibodies such as rheumatoid factor (RF) and anti-SSA/SSB antibodies, as well as hypergammaglobulinemia, reflect B cell hyperactivity. About five percent of patients with SS develop malignant B cell lymphoma, usually of the mucosa-associated lymphoid tissue (MALT) type and most frequently located in the major salivary glands. 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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sjogren's Syndrome
  • Autoimmune Diseases
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Treatment of Sjogren's Syndrome
Experimental:Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject.
Intervention: Biological: Assigned Interventions CD19/BCMA CAR T-cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 11, 2021)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 5, 2024
Estimated Primary Completion Date November 5, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Sjogren's Syndrome 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: He Huang, PhD 86-13605714822 hehuangyu@126.com
Contact: Yongxian Hu, PhD 86-15957162012 huyongxian2000@aliyun.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05085431
Other Study ID Numbers  ICMJE CD19/BCMA-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party He Huang, Zhejiang University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Zhejiang University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Yake Biotechnology Ltd.
Investigators  ICMJE
Principal Investigator: He Huang, PhD First Affiliated Hospital of Zhejiang University
PRS Account Zhejiang University
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP