Study of BCMA/CD70 CAR-T Therapy for Refractory cSLE

NCT06934447 | Recruiting Phase 1 DMC

• 1 other identifier: PBC088
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-BCMA/CD70 CAR-T cells in the treatment of refractory systemic lupus erythematosus.

Conditions

CAR T Cell Therapy; Systemic Lupus Erythematosus; BCMA

Keywords

systemic lupus erythematosus; Chimeric antigen receptor (CAR) T-cell; BCMA

Outcome Measures

Primary Outcomes (2)

• The safety of BCMA/CD70 CAR-T cell therapy in patients with refractory SLE

  Incidence and severity of AEs and SAEs,including changes in laboratory values, Electrocardiograph(ECG) and vital signs assessed by CommonTerminology Criteria for Adverse Events (CTCAE) v5.0.

  3 months

• The efficiency of CAR-T cell therapy in patients with refractory SLE

  Number of patients with SRI-4 response:including SLEDAI-2K ≥ 4-Point improvement, PGA with no worsening (\&amp;amp;amp;lt;0.3-point increase), BILAG 2004 with no new A domain score and no more than 1 new B domain scores. Number of patients with DORIS: including SLEDAI-2K = 0 and a Physician's Global Assessment (PGA) \< 0.5, irrespective of serology, with permitted use of antimalarials, low-dose glucocorticoids (GCs; prednisolone ≤ 5 mg/day), and/or stable immunosuppressives and biologics.

  6 months

Secondary Outcomes (4)

• Cellular kinetics

  6 months

• Autoantibody detection

  24 months

• Pharmacokinetic Outcome AUC

  3 months

• Duration of disease response (DOR)

  24 months

Study Arms (1)

CAR-T treatment group

EXPERIMENTAL

This trial was designed as an open, single-arm, multicenter, dose-increasing trial.

Biological: anti-BCMA/CD70-CAR-T cells

Interventions

anti-BCMA/CD70-CAR-T cells BIOLOGICAL

Three dose groups (0.3×105/kg, 1×105/kg, 3×105/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.

CAR-T treatment group

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age:≥5 years old;
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria；Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ), hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab); or Intolerant to standard treatments;
• SLEDAI 2K score≥8 points;
• The functions of important organs are as follows: Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2；Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN; Lung function: No serious lung lesions, SpO2≥92%;
• No prior CAR-T therapy; or recurrence or poor response after previous treatment with autologous or allogeneic CAR-T targeting CD19 (as assessed by the investigator).
• Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
• Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
• Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

You may not qualify if:

• Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
• Severe acute nephritis: Patients who have accepted or was undergoing renal replacement therapy within 3 months prior to transfusion; Or in the investgator's opinion, patients who is likely to have significant kidney disease within 3 moths of the study which need high dose glucocorticoid (prednisone dose≥1mg/kg/day or equivalent amount of other steriod), cyclophosphamide, or MMF treatment;
• Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
• Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
• Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
• History of organ transplantation or hematopoietic stem cell transplantation, or ≥Grade 2 GVHD within 2 weeks prior to screening；
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
• Received live vaccine within 4 weeks before screening;
• Tested positive in Blood pregnancy test；
• Previous or concurrent malignancy；
• Patients who participated in other clinical study within 1 months prior to enrollment; Any other conditions that the investigators deem it unsuitable for the study.

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead
• Chongqing Precision Biotech Co., Ltd: collaborator

Study Sites (1)

hildren's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

RECRUITING

Related Publications (7)

• Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.

  PMID: 36109639 BACKGROUND

• Charras A, Smith E, Hedrich CM. Systemic Lupus Erythematosus in Children and Young People. Curr Rheumatol Rep. 2021 Feb 10;23(3):20. doi: 10.1007/s11926-021-00985-0.

  PMID: 33569643 BACKGROUND

• Accapezzato D, Caccavale R, Paroli MP, Gioia C, Nguyen BL, Spadea L, Paroli M. Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus. Int J Mol Sci. 2023 Mar 31;24(7):6578. doi: 10.3390/ijms24076578.

  PMID: 37047548 BACKGROUND

• Schett G, Muller F, Taubmann J, Mackensen A, Wang W, Furie RA, Gold R, Haghikia A, Merkel PA, Caricchio R, D'Agostino MA, Locatelli F, June CH, Mougiakakos D. Advancements and challenges in CAR T cell therapy in autoimmune diseases. Nat Rev Rheumatol. 2024 Sep;20(9):531-544. doi: 10.1038/s41584-024-01139-z. Epub 2024 Aug 6.

  PMID: 39107407 BACKGROUND

• Winter O, Dame C, Jundt F, Hiepe F. Pathogenic long-lived plasma cells and their survival niches in autoimmunity, malignancy, and allergy. J Immunol. 2012 Dec 1;189(11):5105-11. doi: 10.4049/jimmunol.1202317.

  PMID: 23169863 BACKGROUND

• Liu Q, Deng Y, Liu X, Zheng Y, Li Q, Cai G, Feng Z, Chen X. Transcriptomic analysis of B cells suggests that CD70 and LY9 may be novel features in patients with systemic lupus erythematosus. Heliyon. 2023 Apr 23;9(5):e15684. doi: 10.1016/j.heliyon.2023.e15684. eCollection 2023 May.

  PMID: 37144201 BACKGROUND

• Wang W, He S, Zhang W, Zhang H, DeStefano VM, Wada M, Pinz K, Deener G, Shah D, Hagag N, Wang M, Hong M, Zeng R, Lan T, Ma Y, Li F, Liang Y, Guo Z, Zou C, Wang M, Ding L, Ma Y, Yuan Y. BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial. Ann Rheum Dis. 2024 Sep 30;83(10):1304-1314. doi: 10.1136/ard-2024-225785.

  PMID: 38777376 BACKGROUND

Related Links

• BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial.
• Transcriptomic analysis of B cells suggests that CD70 and LY9 may be novel features in patients with systemic lupus erythematosus.
• Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus.
• Systemic Lupus Erythematosus in Children and Young People.
• Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus
• Pathogenic long-lived plasma cells and their survival niches in autoimmunity, malignancy, and allergy.

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jianhua Mao, MD

  Zhejiang University School of Medicine Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianhua Mao, MD

CONTACT

13516819071; maojh88@zju.edu.cn

Xue He

CONTACT

15088688407; hexue1119@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Treatment of pediatric patients with refractory systemic lupus erythematosus using BMCA/CD70-targeted CAR T cells

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 18, 2025
• Study Start: April 25, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)