CAR T-cell Therapy Targeting CD19 and BCMA in Patients With B Cell Mediated Autoimmune Disease

A Clinical Study Evaluating the Safety and Preliminary Efficacy of Universal Allogeneic CAR T-cell Therapy Targeting CD19 and BCMA in Patients With B Cell Mediated Autoimmune Disease

CAR T-cell Therapy Targeting CD19 and BCMA in Patients With B cell mediated autoimmune disease.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases; IgA Nephropathy (IgAN); ANCA Associated Systemic Vasculitis; Systemic Sclerosis (SSc); Multi-Drug Resistant Nephrotic Syndrome; Systemic Lupus Erthematosus (SLE)
• Intervention / Treatment: Biological: UCAR T-cell

Detailed Description

This is an investigator-initiated trial to evaluate the safety and efficacy of universal allogeneic anti-CD19/BCMA CAR T-cells in Patients With B cell mediated autoimmune disease.

Study intervention consists of a single infusion of universal allogeneic CART-cells administered intravenously after a lymphodepleting therapy regimen consisting of cyclophosphamide. Interim analysis will be performed when participants finish the visit 12 and 24 weeks after CART-cell infusion.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jianhua Mao, PhD; Phone Number: 13516819071; Email: maojh88@zju.edu.cn
• Study Contact Backup: Name: Qiuyu Li, MD; Phone Number: 17794588355; Email: liqiuyu1992@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Recruiting
      • Children's Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Common Inclusion Criteria:

1. Major organ function must meet the following criteria (exceptions allowed for abnormalities related to autoimmune disease activity):

1. Bone Marrow Function: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; b. Hemoglobin ≥ 60 g/L; c. Platelet count ≥ 30 × 10⁹/L.
2. Hepatic Function: ALT ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); AST ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); Total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for Gilbert syndrome).
3. Renal Function: eGFR ≥ 30 mL/min/1.73 m².(Participants with eGFR < 30 mL/min/1.73 m² and/or those receiving renal replacement therapy may be considered eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant or guardian provides fully informed consent.)
4. Cardiac Function: Echocardiography shows no significant structural abnormalities and left ventricular ejection fraction (LVEF) ≥ 55%.
5. Pulmonary Function: No severe pulmonary disease, and SpO₂ ≥ 92%. 2. Women of childbearing potential must use medically acceptable contraception or practice abstinence during the study treatment period and for at least 12 months after the end of study treatment.

3. Informed consent: The participant (and guardian if the participant is a minor) must provide written informed consent, indicating understanding of the study purpose and procedures and willingness to participate.

Disease-Specific Inclusion Criteria

SLE:

1. Age ≥ 5 years.
2. Meets the 2012 SLICC or 2019 EULAR/ACR classification criteria for SLE.

3. Must meet at least one of the following adequate treatment conditions:

   a) Treated with glucocorticoids (≥1 mg/kg/day prednisone or equivalent) plus one or more immunomodulatory agents (including cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, thalidomide, belimumab, or rituximab) for at least 3 months.

   b) Patients unable to tolerate conventional therapy may be eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant (or guardian if minor) provides fully informed consent.

   c) Patients who cannot taper glucocorticoids to ≤5 mg/day after 6 months of conventional therapy.

4. SLE disease activity: SLEDAI-2K score ≥ 8; or SLEDAI ≥ 6 plus at least one BILAG-2004 category A or two category B scores, or both.
5. No occurrence of macrophage activation syndrome within 1 month prior to screening.
6. Occurrence of CNS lupus symptoms requiring intervention within 60 days prior to screening, including seizures, psychosis, cerebrovascular events, etc.

MDR-SRNS

1. Age ≥3 years old, gender unlimited.
2. Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes #KDIGO# Guidelines;

3. Must meet at least one of the following adequate treatment conditions:

   a) have not achieved a complete response after 12 months of treatment with two standard doses of hormone replacement drugs with different mechanisms of action or relapse of disease activity after remission(at least one of the two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus, Other replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitacept or rituximab).

   b) if no remission has been achieved after 3 to 6 months of adequate treatment with one calcineurin- inhibitor. The researcher judges that the benefits outweigh the risks and the patient or guardian has fully informed consent, the patient can be considered for inclusion.

   c) Patients unable to tolerate conventional therapy may be eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant (or guardian if minor) provides fully informed consent.

   d) Patients with other diseases, such as systemic lupus erythematosus, requiring long-term systemic treatment with glucocorticoids or immunosuppressants, may be considered for inclusion after the investigator determines that the benefits outweigh the risks, and the patient or guardian has fully informed consent.

4. Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);

IgA nephropathy

1. Age: ≥ 5 years old, gender unlimited;
2. IgA nephropathy pathologically confirmed by renal biopsy;

3. Angiotensin-Converting Enzyme Inhibitors (ACE) or angiotensin receptor blocker (ARB) treated for at least 3 months and meet at least one of the following requirements:

   a) Combination or sequential treatment with steroids and at least one immunosuppressant or biologic for ≥ 3 months; and 24-hour urine protein quantification ≥500mg or UPCR≥0.5mg/mg; b) >50% decline in eGFR within 3 months; c) Patients who are unable to tolerate conventional treatment and for whom the investigator determines the benefits outweigh the risks and who have obtained fully informed consent from the patient or guardian may be considered for inclusion;

4. Exclude subjects with other secondary causes; exclude patients with uncontrolled blood pressure.

Refractory/Relapsed/Progressive Systemic Sclerosis:

1. Age: ≥ 5 years old, gender unlimited;
2. Scleroderma fulfilling the 2013 ACR classification criteria
3. Positive scleroderma-related antibodies.
4. Modified Rodnan Skin Score (mRSS) ≥ 15 (total score 51).

5. Must meet at least one of the following adequate treatment conditions:

   1. Treated with glucocorticoids (≥0.5 mg/kg/day) plus at least one immunomodulatory agent (including antimalarials, cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, or biologics such as rituximab, belimumab, thalidomide) for more than 3 months without significant improvement.
   2. Meets criteria for rapidly progressive disease (see Appendix 1) and is unresponsive to standard therapy; participant may be enrolled if the investigator determines that potential benefit outweighs risk and informed consent is obtained.
   3. Patients unable to tolerate conventional therapy may be eligible if the investigator determines that potential benefit outweighs risk and informed consent is obtained.
6. Presence of severe pulmonary arterial hypertension (PAH), defined as a mean pulmonary arterial pressure >45 mmHg, or other severe involvement of major organs will be exclude.

Refractory/Relapsed ANCA-Associated Vasculitis:

1. Age: ≥ 5 years old, gender unlimited;
2. Meets the diagnostic criteria for ANCA-associated vasculitis according to the 2007 European Medicines Agency (EMA) algorithm or the 2022 ACR/EULAR classification criteria, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).
3. Has received glucocorticoids (≥1 mg/kg/day) in combination with at least one immunosuppressant or biologic agent (including cyclophosphamide, rituximab, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, belimumab, telitacicept, etc.) for at least 3 months without achieving sustained remission, or has experienced relapse after remission;or meets the criteria for severe vasculitis (Appendix 1), with inadequate response to standard-of-care therapy, and may be considered for enrollment if the investigator determines that the potential benefits outweigh the risks and the patient or legal guardian provides fully informed consent.
4. Evidence of active vasculitis meeting the following criteria: For participants <18 years of age: Pediatric Vasculitis Activity Score (PVAS) ≥10 (total score 63); For participants ≥18 years of age: Birmingham Vasculitis Activity Score (BVAS) ≥10 (total score 63); indicating active vasculitis.
5. Exclusion Criterion: Presence of alveolar hemorrhage requiring ventilatory support for more than one week.

Exclusion Criteria:

• 1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, tocilizumab), or subjects with a history of severe allergic reactions.

  2. Subjects with grade III or IV heart failure (NYHA classification). 3. 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.

  4. Uncontrollable infection, or active infection that requires systemic treatment at screening.

  5. Had active pulmonary tuberculosis at screening. 6. 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.

  7. History of severe herpes infection prior to screening, such as herpetic encephalitis, ocular herpes, or disseminated herpes; Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening.

  8. Patients had active central nervous system disease. 9. Patients with malignant diseases such as tumors before screening. 10. Secondary or congenital immunodeficiency. 11. History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of QT-019B, except for lupus.

  12. Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening.

  13. Received live vaccine within 4 weeks before screening. 14. Tested positive in Blood pregnancy test. 15. Patients who had participated in other clinical trials and received any intervention within 3 months before enrollment.

  16. Any abnormal laboratory test results judged by the investigator to be clinically significant and prevent the subject from participating in the study. Laboratory test values that are out of range and not of clinical significance will not be considered as exclusion criteria.

  17. Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UCAR T-cell group; Universal allogeneic anti-CD19/BCMA CAR T-cells	Biological: UCAR T-cell; Universal allogeneic anti-CD19/BCMA CAR T-cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number and severity of dose-limiting toxicity (DLT) events	The number and severity of dose-limiting toxicity (DLT) events DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, and the ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.	Within 28 Days After UCAR T-cell Infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of CAR-T cells [PK parameter]	The peak plasma concentration (Cmax) of amplified UCAR-T cells in peripheral blood after infusion.	Within 28 Days After UCAR T-cell Infusion
Tmax of CAR-T cells [PK parameter]	The time of amplified UCAR-T cells in peripheral blood to reach the maximum concentration (Tmax).	Within 28 Days After UCAR T-cell Infusion
AUC 0-28d of UCAR-T cells [PK parameter]	The area under the plasma concentration-time curve from 0 to 28 days after infusion (AUC0-28d).	Within 28 Days After UCAR T-cell Infusion
The degree of B cell depletion [PD parameter]	The degree of B cell depletion at various time points.	Up to 12 Months After UCAR T-cell Infusion
The concentration levels of IL-6 [PD parameter]	UCAR-T-related serum cytokines include IL-6.	Up to 12 Months After UCAR T-cell Infusion
The changes of anti-ds-DNA antibody after infusion [PD parameter ]		Up to 12 Months After UCAR T-cell Infusion

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: November 30, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 31, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; Systemic Sclerosis (SSc); Multi-Drug Resistant Nephrotic Syndrome; Systemic Lupus Erthematosus; IgAN - IgA Nephropathy; ANCA-Associated Vasculitis (AAV)
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Glomerulonephritis; Nephritis; Nephrosis; Systemic Vasculitis; Skin and Connective Tissue Diseases; Autoimmune Diseases; Scleroderma, Systemic; Glomerulonephritis, IGA; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Nephrotic Syndrome
• Other Study ID Numbers: QH-ZE-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No