Anti-BCMA-CD19 CAR-T therapy for relapsed or refractory IgG4-related disease

Exploratory Clinical Study of Anti-BCMA-CD19 CAR-T Cell Therapy for Relapsed/Refractory IgG4-Related Disease

This trial will test a personalized CAR-T cell therapy that targets BCMA and CD19 in adults (18–75) whose IgG4-related disease has come back or not responded to standard treatments like steroids or rituximab.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (other)
• Drugs / interventions: rituximab, CAR-T, chemotherapy, chimeric antigen receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07148791 on ClinicalTrials.gov

What this trial studies

This Phase 2, open-label, single-arm trial uses a 3+3 dose-escalation design to test autologous anti-BCMA-CD19 CAR-T cells in adults with relapsed or refractory IgG4-related disease. Eligible participants undergo leukapheresis to collect their immune cells, receive short-term lymphodepleting chemotherapy, and then a single intravenous infusion of the engineered CAR-T cells. Safety (adverse events) and changes in disease activity scores are checked at 12 and 26 weeks with clinic visits, blood tests, and imaging, and participants may be followed for up to one year. The approach aims to deplete pathogenic CD19+ B cells, plasmablasts, and BCMA-expressing plasma cells that can persist despite conventional B-cell–directed therapies.

Who should consider this trial

Good fit: Adults 18–75 who meet the 2019 ACR/EULAR criteria for IgG4-RD, have involvement of two or more key organ sites, and whose disease is relapsed or refractory after glucocorticoid and/or rituximab therapy with adequate organ function are the intended participants.

Not a fit: Patients with well-controlled or single-organ IgG4-RD, those with severe organ dysfunction that prevents safe lymphodepletion, active serious infections, or who fail marrow/hepatic/renal entry criteria are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this therapy could produce deeper and longer-lasting remissions for patients with treatment-resistant IgG4-RD by eliminating disease-causing B-lineage cells.

How similar studies have performed: CAR-T therapies targeting CD19 or BCMA have shown strong activity in B-cell malignancies and encouraging early signals in some refractory autoimmune cases, but dual-target anti-BCMA/CD19 CAR-T for IgG4-RD is novel and remains largely untested in larger studies.

Eligibility criteria

Inclusion Criteria:

To participate, subjects must meet all of the following criteria:

1. Aged 18 to 75 years, inclusive, regardless of sex.
2. Meet the 2019 ACR/EULAR classification criteria for IgG4-related disease.
3. Involvement of two or more important systems/sites (including but not limited to the pancreas, bile ducts, kidneys and dura mater).
4. 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.
5. 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.
6. 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.
7. Voluntary participation in this clinical study with signed informed consent and willingness to comply with study procedures and follow-up.
8. Patent superficial peripheral veins adequate for intravenous infusion.

Exclusion Criteria:

Subjects will be excluded if any of the following criteria are met:

1. History of severe drug allergy or allergic constitution.
2. Current or suspected uncontrollable or treatment-requiring fungal, bacterial, viral or other infections.
3. Central nervous system disease (excluding disease-related epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis).
4. Cardiac insufficiency that precludes participation.
5. Congenital immunoglobulin deficiency.
6. Congenital malformation or nutritional disorder causing severe organ impairment.
7. History of malignancy within the past five years.
8. End-stage renal failure.
9. 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.
10. Psychiatric disorders or severe cognitive impairment.
11. Participation in other clinical trials within three months before enrollment.
12. Receipt of any investigational drug within 12 weeks before screening or within five half-lives of the agent (whichever is longer).
13. Pregnant or intending to become pregnant.
14. Any other reason deemed by the investigator to preclude enrollment.

Where this trial is running

Beijing, Beijing Municipality

• Department of Rheumatology and Immunology, the First Medical Center, Chinese PLA General Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Principal investigator: JIAN ZHU, M.D./Ph.D. — Department of Rheumatology and Immunology, the First Medical Center, Chinese PLA General Hospital, Beijing
• Study coordinator: YIWEN WANG, M.D.

Conditions: IgG4 Related Disease, B-cell Mediated Autoimmune Disorders, IgG4 related disease, CAR-T therapy, BCMA/CD19 CAR-T