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Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients

Sponsor
RenJi Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05858684
Collaborator
Gracell Biotechnology Shanghai Co., Ltd. (Industry)
18
Enrollment
1
Location
1
Arm
24
Anticipated Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an early exploratory phase, single arm, non-randomized, open label, treatment study trial to determine the maximum tolerated dose of GC012F injection (CD19-BCMA CAR-T cells) in patients with refractory systemic lupus erythematosus.

Condition or Disease Intervention/Treatment Phase
  • Drug: GC012F injection
 Early Phase 1

Detailed Description

Systemic lupus erythematosus (SLE) is a kind of autoimmune diseases mediated by autoantibody-forming immune complexes, which involving multiple systems and organs.

Autoreactive B cells can self-activate and differentiate into plasma cells releasing large amounts of autoantibodies, while they can also present their own antigens to autoimmune T cells, thus activating T cells and promoting the release of inflammatory factors.

Traditional SLE treatment aims at long-term remission, while, CD19- BCMA CAR-T cells can theoretically completely deplete abnormal antibody-producing B cells, allowing immune rebuilding and restoring the patient's normal immune function, achieving drug-free survival, which fully reflects the application prospects of CAR-T therapy in SLE.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients
Anticipated Study Start Date :
May 11, 2023
Anticipated Primary Completion Date :
Nov 10, 2023
Anticipated Study Completion Date :
May 10, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: GC012F injection (CD19-BCMA CAR-T cells)

Dose escalation phase: DL-1：0.5±20%×10^5/kg, DL1：1±20%×10^5/kg, DL2：2±20%×10^5/kg DL3：3±20%×10^5/kg

Drug: GC012F injection
Each subject will receive GC012F injection (CD19-BCMA CAR-T cells) by intravenous infusion on Day 0.
Other Names:
  • CD19-BCMA CAR-T cells

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The proportion of subjects with DLT [Within 28 days after GC012F injection infusion]

      DLT definition is dose-limiting toxicity

    2. The proportion of subjects with adverse events [Within 12 weeks after GC012F injection infusion]

      All adverse events were evaluated according to NCI-CTCAE v5.0 criteria

    Secondary Outcome Measures

    1. Proportion of subjects achieving SRI-4 [4, 8, 12 and 24 weeks after GC012F injection infusion]

      SELEAN-SLEDAI，BILAG，PGA

    2. Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable) [After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24]]

      Test method: flow cytometry and qPCR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. 18-70 years old;

    2. Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;

    3. SELENA-SLEDAI≥8;

    4. Patients with CD19+ B-cell;

    5. Hemoglobin≥85 g/L;

    6. WBC≥2.5×10^9/L

    7. NEUT≥1×10^9/L;

    8. BPC≥50×10^9/L;

    9. AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%;

    10. Adequate venous access for apheresis, and no other contraindications for leukapheresis;

    11. Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline. Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion.

    12. Agree to attend follow-up visits as required;

    13. Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative;

    Exclusion Criteria:

    1. Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L) within 8 weeks prior to leukapheresis, or subjects who need hemodialysis;

    2. CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts;

    3. Patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system;

    4. Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;

    5. Received immunosuppressive therapy within 1 week prior to leukapheresis;

    6. Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus; Patients with syphilis infection;

    7. The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening;

    8. Received live vaccine treatment within 4 weeks prior to screening;

    9. Severe allergies or hypersensitivity;

    10. Contraindication to cyclophosphamide in combination with fludarabine;

    11. Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion;

    12. cannula or drainage tubes other than central venous catheters;

    13. Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;

    14. Subjects with prior CD19 or BCMA-targeted therapy

    15. Participated in any clinical study within 3 months prior to enrollment

    16. Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS>5yr; Cervical Cancer in situ; Bladder Cancer; Breast Cancer;

    17. Any situations that the investigator believes the patients are not suitable for the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai JiaoTong University Shanghai Shanghai China 200001

    Sponsors and Collaborators

    • RenJi Hospital
    • Gracell Biotechnology Shanghai Co., Ltd.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Qiong Fu, Professor, RenJi Hospital
    ClinicalTrials.gov Identifier:
    NCT05858684
    Other Study ID Numbers:
    • GC012F-615
    First Posted:
    May 15, 2023
    Last Update Posted:
    May 15, 2023
    Last Verified:
    May 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lupus Erythematosus, Systemic

    Study Results

    No Results Posted as of May 15, 2023