Exploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease

NCT07148791 | Recruiting Phase 2 DMC

• 1 other identifier: BC19IGG4
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the safety and potential benefit of a new immune cell therapy called anti-BCMA-CD19 CAR-T cells in adults (18-75 years) with IgG4-related disease (IgG4-RD) that has come back or not improved after standard treatments such as glucocorticoids or rituximab. The main questions this study aims to answer are:

• What medical problems (side effects) occur after receiving anti-BCMA-CD19 CAR-T cell therapy?
• Does anti-BCMA-CD19 CAR-T cell therapy improve IgG4-RD disease activity scores at 12 weeks and 26 weeks? Participants will:
• Have their own blood immune cells collected by a procedure called leukapheresis
• Receive short-term chemotherapy to prepare the immune system
• Receive one intravenous infusion of anti-BCMA-CD19 CAR-T cells
• Return for regular clinic visits over 26 weeks for safety checks, blood tests, and imaging
• May be followed for up to one year in total

Conditions

IgG4 Related Disease; B-cell Mediated Autoimmune Disorders

Keywords

IgG4 related disease; CAR-T therapy; BCMA/CD19 CAR-T

Outcome Measures

Primary Outcomes (2)

• Safety - Incidence of Dose-Limiting Toxicity (DLT) and Adverse Events Related to CAR-T Cells

  Any grade ≥3 toxicity related to CAR-T cells within 28 days post-infusion is considered a DLT, except: * Grade 3 CRS resolving to ≤ grade 2 within 3 days; * Grade 3/4 TLS \<7 days; * Hematologic: grade 3 neutropenia/anemia/thrombocytopenia at any time or grade 4 \<14 days (\<21 days for thrombocytopenia); other cytopenias excluded; * Non-hematologic: fever (incl. febrile neutropenia), grade 3 diarrhea \<7 days, grade 3 nausea/vomiting \<7 days, grade 3 fatigue \<7 days; * Grade 3/4 elevations in liver enzymes, bilirubin, creatinine, or BUN \<7 days; * Asymptomatic lipase elevation without pancreatitis; * Asymptomatic grade 3 non-hematologic lab abnormality reversible \<7 days (to baseline or ≤ grade 2). Safety monitoring includes AEs, SAEs, AESIs, CRS, and ICANS, with grading and frequency recorded.

  Baseline to Week 26

• Efficacy - Changes in IgG4-RD RI

  IgG4-RD Responder Index is a validated score used to assess disease activity

  Baseline, Week 12 and Week 26

Secondary Outcomes (13)

• PK: Cmax of CAR-T Cells

  Baseline to Week 26

• PK: Tmax of CAR-T Cells

  Baseline to Week 26

• PK: AUC0-28d of CAR-T Cells

  Baseline, Week 4

• PK: AUC0-90d of CAR-T Cells

  Baseline, W12

• PK: Persistence (Tlast) of CAR-T Cells

  Baseline to Week 26

Other Outcomes (4)

• Peripheral Blood Immune Cell Subsets

  Baseline and Week 26

• B-cell Subpopulations in Lesion Tissue

  Baseline and Week 26

• Plasma Cytokine and Chemokine Levels

  Baseline and Week 26

Study Arms (1)

Anti-BCMA-CD19 CAR-T cells

EXPERIMENTAL

Participants will undergo leukapheresis for autologous T-cell collection, followed by ex vivo transduction with a lentiviral vector encoding a dual-target CAR against BCMA and CD19. After lymphodepletion chemotherapy with fludarabine (30 mg/m²/day) and cyclophosphamide (250 mg/m²/day) for 3 consecutive days, participants will receive a single intravenous infusion of the manufactured CAR-T cells at the assigned dose level. Post-infusion, participants will be monitored for safety, tolerability, and preliminary efficacy through Week 52.

Biological: Anti-BCMA-CD19 CAR-T cells

Interventions

Anti-BCMA-CD19 CAR-T cells BIOLOGICAL

Anti-BCMA-CD19 CAR-T cell injection is an autologous, dual-target chimeric antigen receptor T-cell therapy designed to target CD19 and BCMA antigens. Peripheral blood mononuclear cells (PBMCs) are collected from each participant and modified ex vivo using lentiviral transduction to express the CAR construct. Lymphodepletion with cyclophosphamide (250 mg/m\^2/day, IV) and fludarabine (30 mg/m\^2/day, IV) is administered for 3 days (Day -5 to Day -3). The doses of fludarabine and cyclophosphamide may be adjusted based on the patient's clinical condition. CAR-T cells are infused intravenously on Day 0 at one of three dose levels (1x10\^6, 2x10\^6, or 3x10\^6 CAR+ T cells/kg, ±20%). This product is being investigated in patients with relapsed or refractory IgG4-related disease (IgG4-RD) to assess safety and preliminary efficacy.

Also known as: BC19, CD19/BCMA dual-target CAR-T cell therapy

Anti-BCMA-CD19 CAR-T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To participate, subjects must meet all of the following criteria:
• Aged 18 to 75 years, inclusive, regardless of sex.
• Meet the 2019 ACR/EULAR classification criteria for IgG4-related disease.
• Involvement of two or more important systems/sites (including but not limited to the pancreas, bile ducts, kidneys and dura mater).
• Relapsed or refractory IgG4-RD: The disease either remains active after 3 months of glucocorticoid and/or rituximab therapy or relapses within 6 months post-treatment.
• Important organ function meeting the following conditions:
• Bone marrow: (i) neutrophil count ≥1×10\^9/L (excluding disease-related neutropenia); (ii) hemoglobin ≥60 g/L.
• Hepatic function: ALT≤3×ULN (elevation caused by disease may be excluded); AST≤3×ULN (elevation caused by disease may be excluded); TBIL≤1.5×ULN (elevation caused by disease may be excluded).
• Renal function: creatinine clearance (Cockcroft-Gault formula) ≥30 ml/min (excluding acute decline due to disease).
• Coagulation: international normalized ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) ≤ 1.5×ULN
• Cardiac function: stable hemodynamics.
• Women of childbearing potential and male subjects with partners of childbearing potential must use medically accepted contraception or abstain during study treatment and for at least 12 months after the end of treatment. Women of childbearing potential must have a negative serum HCG test within 7 days before enrollment and must not be breastfeeding.
• Voluntary participation in this clinical study with signed informed consent and willingness to comply with study procedures and follow-up.
• Patent superficial peripheral veins adequate for intravenous infusion.

You may not qualify if:

• Subjects will be excluded if any of the following criteria are met:
• History of severe drug allergy or allergic constitution.
• Current or suspected uncontrollable or treatment-requiring fungal, bacterial, viral or other infections.
• Central nervous system disease (excluding disease-related epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis).
• Cardiac insufficiency that precludes participation.
• Congenital immunoglobulin deficiency.
• Congenital malformation or nutritional disorder causing severe organ impairment.
• History of malignancy within the past five years.
• End-stage renal failure.
• Positive hepatitis B surface antigen and hepatitis B core antibody with HBV-DNA titers above the assay limit of detection; positive hepatitis C antibody with HCV-RNA positivity; positive human immunodeficiency virus antibody; positive syphilis serology.
• Psychiatric disorders or severe cognitive impairment.
• Participation in other clinical trials within three months before enrollment.
• Receipt of any investigational drug within 12 weeks before screening or within five half-lives of the agent (whichever is longer).
• Pregnant or intending to become pregnant.
• Any other reason deemed by the investigator to preclude enrollment.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• Xuzhou Medical University: collaborator

Study Sites (1)

Department of Rheumatology and Immunology, the First Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Related Publications (4)

• Sun Y, Huang S, Zhang B, Peng Y, Lu H, Jia Y, Sun R, Zhang F, Zhou J, Peng L, Li M, Zhang W, Fei Y. Efficacy and safety of anti-CD19 CAR-T in a mouse model of IgG4-related disease. Int Immunopharmacol. 2025 Jan 3;145:113779. doi: 10.1016/j.intimp.2024.113779. Epub 2024 Dec 12.

  PMID: 39672025 RESULT

• Zhang Y, Liu D, Zhang Z, Huang X, Cao J, Wang G, Du X, Wang Z, Yang M, Luo T, Liu S, Zhang W, Sheng Y, Li H, Zhang W, Chen H, Zhang S, Wang X, Meng W, Zong S, Shi M, Zheng J, Cui G. Bispecific BCMA/CD19 targeted CAR-T cell therapy forces sustained disappearance of symptoms and anti-acetylcholine receptor antibodies in refractory myasthenia gravis: a case report. J Neurol. 2024 Jul;271(7):4655-4659. doi: 10.1007/s00415-024-12367-4. Epub 2024 Apr 11. No abstract available.

  PMID: 38602546 RESULT

• Shi M, Wang J, Huang H, Liu D, Cheng H, Wang X, Chen W, Yan Z, Sang W, Qi K, Li D, Zhu F, Li Z, Qiao J, Wu Q, Zeng L, Fei X, Gu W, Miao Y, Xu K, Zheng J, Cao J. Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial. Nat Commun. 2024 Apr 20;15(1):3371. doi: 10.1038/s41467-024-47801-8.

  PMID: 38643278 RESULT

• Wang Y, Cao J, Gu W, Shi M, Lan J, Yan Z, Jin L, Xia J, Ma S, Liu Y, Li H, Pan B, Chen W, Fei X, Wang C, Xie X, Yu L, Wang G, Li H, Jing G, Cheng H, Zhu F, Sun H, Sang W, Li D, Li Z, Zheng J, Xu K. Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. J Clin Oncol. 2022 Jul 10;40(20):2246-2256. doi: 10.1200/JCO.21.01676. Epub 2022 Mar 25.

  PMID: 35333600 RESULT

MeSH Terms

Conditions

Immunoglobulin G4-Related Disease

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Study Officials

• JIAN ZHU, M.D./Ph.D.

  Department of Rheumatology and Immunology, the First Medical Center, Chinese PLA General Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

YIWEN WANG, M.D.

CONTACT

+86 010-55499314; yiwenvera@163.com

YUFEI GUO, M.M.

CONTACT

+86 010-55499314; dt_guoyf0412@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician and Professor, Department of Rheumatology and Immunology, First Medical Center, Chinese PLA General Hospital

Model Details: This is an open-label, single-arm, exploratory interventional study using a 3+3 dose-escalation design. Adults with relapsed or refractory IgG4-related disease will receive autologous anti-BCMA-CD19 CAR-T cells. The study includes a lymphodepletion phase, a cell infusion phase, and serial efficacy and safety assessments through Week 26. Three dose levels (1x10\^6, 2x10\^6, and 3x10\^6 CAR+ T cells/kg) will be evaluated sequentially. No control group is included.

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 29, 2025
• Study Start: September 5, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)