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

• ClinicalTrials.gov Identifier: NCT05858684
• Recruitment Status: Recruiting
• First Posted: May 15, 2023
• Last Update Posted: May 15, 2023
• Sponsor: RenJi Hospital
• Collaborator: Gracell Biotechnology Shanghai Co., Ltd.
• Information provided by (Responsible Party): Qiong Fu, RenJi Hospital

Tracking Information

• First Submitted Date: May 5, 2023
• First Posted Date: May 15, 2023
• Last Update Posted Date: May 15, 2023
• Estimated Study Start Date: May 11, 2023
• Estimated Primary Completion Date: November 10, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 5, 2023)

• The proportion of subjects with DLT [ Time Frame: Within 28 days after GC012F injection infusion ]
  DLT definition is dose-limiting toxicity
• The proportion of subjects with adverse events [ Time Frame: Within 12 weeks after GC012F injection infusion ]
  All adverse events were evaluated according to NCI-CTCAE v5.0 criteria

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: May 5, 2023)

• Proportion of subjects achieving SRI-4 [ Time Frame: 4, 8, 12 and 24 weeks after GC012F injection infusion ]
  SELEAN-SLEDAI，BILAG，PGA
• Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable) [ Time Frame: After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24] ]
  Test method: flow cytometry and qPCR

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients
• Official Title: Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients
• 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.

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 Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: CAR-T Cell Therapy

Intervention

Drug: GC012F injection

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

Other Name: CD19-BCMA CAR-T cells

Study Arms

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

Intervention: Drug: GC012F injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 5, 2023): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 10, 2025
• Estimated Primary Completion Date: November 10, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Qiong Fu, PhD; 13585603288; fuqiong5@163.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05858684
• Other Study ID Numbers: GC012F-615
• Has Data Monitoring Committee: Not Provided

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

• Plan to Share IPD: No

• Current Responsible Party: Qiong Fu, RenJi Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: RenJi Hospital
• Original Study Sponsor: Same as current
• Collaborators: Gracell Biotechnology Shanghai Co., Ltd.
• Investigators: Not Provided
• PRS Account: RenJi Hospital
• Verification Date: May 2023