Efficacy and Safety of CD19 CAR-γδ T Cells in the Treatment of Relapsed/Refractory Autoimmune Nephropathy

NCT07535138 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: KY20262098-C-1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm, single-center, open-label, dose-escalation exploratory clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of CD19 CAR-γδ T cells. The subjects enrolled in this study are patients with relapsed/refractory autoimmune nephropathy, including lupus nephritis, IgA nephropathy, and membranous nephropathy. This study adopts a standard "3+3" design to assess the recommended dose (RD) and identify dose-limiting toxicities (DLTs). The treatment process is as follows: subjects who meet the inclusion criteria will receive lymphodepletion conditioning, followed by a single intravenous infusion of CD19 CAR-γδ T cells. The primary objective of this study is to evaluate the safety profile of this cellular therapy, including the incidence of DLTs, maximum tolerated dose (MTD) or RD, as well as the incidence and severity of treatment-related adverse events and clinically significant abnormal laboratory test results after CAR-γδ T cell infusion (including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)). The planned follow-up duration of this study is 1 years.

Conditions

Membranous Nephropathy; Lupus Nephritis (LN); IgA Nephropathy (IgAN)

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicities (DLTs)

  The number, frequency, and severity of DLTs experienced by subjects after the first infusion of CD19 CAR-γδ T cells. DLTs are defined by NCI-CTCAE 5.0 and ASTCT consensus for CRS and neurotoxicity.

  Day 0 to Day 28 post-infusion

• Incidence of Adverse Events (AEs)

  Evaluation of the number, frequency, and severity of all adverse events, including Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs).

  Up to Month 12 post-infusion

Secondary Outcomes (12)

• Preliminary Clinical Efficacy for Lupus Nephritis

  Month 3, Month 6, Month 9, Month 12,

• Preliminary Clinical Efficacy for IgA Nephropathy

  Month 3, Month 6, Month 9, Month 12,

• Preliminary Clinical Efficacy for Membranous Nephropathy

  Month 3, Month 6, Month 9, Month 12

• The degree of B cell depletion

  Up to 12 Months After CAR-γδT Cell Infusion

• Urine Protein

  Week 2, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 12

Study Arms (1)

CAR-T Cell Therapy Group

EXPERIMENTAL

This is a single-arm, open-label study in which all patients receive infusions of different doses of CD19 CAR-γδ T cells in accordance with the "3+3" dose-escalation principle.

Biological: CD19 CAR-γδ T cell

Interventions

CD19 CAR-γδ T cell BIOLOGICAL

Prior to CAR-γδ T cell infusion, patients will receive lymphodepleting chemotherapy consisting of cyclophosphamide combined with fludarabine, followed by infusion of CD19 CAR-γδ T cells at the assigned dose level per their dose-escalation cohort, with target total cell doses of 3×10\^7, 1×10\^8, and 3×10\^8 cells, respectively.

CAR-T Cell Therapy Group

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years and ≤65 years;
• Agree to participate in this study and sign the informed consent form;
• Major organ function must meet the following criteria (exceptions are allowed for abnormalities associated with active autoimmune diseases):
• Liver function: ALT, AST or ALP level ≤3 × ULN (upper limit of normal), bilirubin ≤2 × ULN;
• Renal function: eGFR ≥30 mL/min/1.73m²;
• Pulmonary function: blood oxygen saturation (without oxygen inhalation) ≥92%;
• Cardiac function: hemodynamically stable, left ventricular ejection fraction (LVEF) ≥55%;
• Peripheral blood function: neutrophil count ≥1×10\^9/L, hemoglobin ≥60 g/L, platelets ≥30×10\^9/L;
• Subjects of childbearing potential (including males and females) must agree to use medically acceptable effective contraceptive measures during the study period and for at least 1 year after CAR-T cell infusion.
• Primary Membranous Nephropathy:
• Diagnosed with primary membranous nephropathy (PMN) by renal biopsy within 18 months before screening;
• Meet the current clinical criteria for refractory PMN: after 6 months of systemic treatment with immunosuppressive regimens recommended by the KDIGO guidelines (including steroids, cyclophosphamide, calcineurin inhibitors, anti-CD20 monoclonal antibodies, etc.), persistent 24-hour urinary protein ≥3.5g and not reduced to less than 50% of the baseline level;
• Relapsed PMN: after achieving complete or partial remission with the above immunosuppressive regimens, 24-hour urinary protein re-elevated to ≥ 3.5g.
• Lupus Nephritis:
• Diagnosed with systemic lupus erythematosus (SLE) before screening, in accordance with the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus;

You may not qualify if:

• Subjects with life-threatening conditions (e.g., catastrophic antiphospholipid syndrome, acute severe renal failure) assessed by the investigator as unsuitable for enrollment in this study;
• History of alcohol or drug abuse within 24 weeks prior to screening;
• History of malignant tumors other than B-cell lymphoma, except for the following: malignancies confirmed to be cured or in remission for ≥5 years, radically resected basal cell carcinoma or squamous cell carcinoma of the skin, and carcinoma in situ at any site;
• Major surgery (including joint surgery) within 24 weeks prior to screening, or planned surgery within 24 weeks after enrollment;
• Complicated with overlapping mixed connective tissue disease, or other diseases that affect the assessment of disease activity;
• Active hepatitis B or hepatitis C virus infection, defined as: subjects positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with peripheral blood high-sensitivity HBV DNA quantification above the lower limit of detection; subjects with peripheral blood high-sensitivity HBV DNA quantification below the lower limit of detection may be enrolled only if the investigator provides appropriate prophylactic antiviral therapy; individuals positive for hepatitis C virus (HCV) antibody with positive peripheral blood high-sensitivity HCV RNA quantification;
• Coinfection with human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV), Treponema pallidum, cytomegalovirus (CMV), or complicated with selective IgA deficiency;
• Uncontrolled active infection (e.g., active pulmonary tuberculosis, etc., excluding simple urinary tract infection and bacterial pharyngitis); prophylactic administration of antibiotics, antiviral or antifungal agents is permitted;
• Clinical signs of herpes or varicella-zoster virus infection (especially varicella, herpes zoster) within 12 weeks prior to screening;
• History of major cardiovascular diseases within 6 months prior to screening, including NYHA class III or IV heart failure, myocardial infarction, angioplasty or stenting, unstable angina, uncontrolled or symptomatic atrial arrhythmia, any ventricular arrhythmia, or other clinically significant cardiac diseases;
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to screening;
• Central nervous system disorders caused by autoimmune or non-autoimmune diseases (including epilepsy, psychiatric disorders, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis);
• Pregnant or lactating women;
• Hypersensitivity to any component of the CAR-γδ T cell product (including fludarabine, cyclophosphamide, tocilizumab);
• Administration of live vaccines within 6 weeks prior to the start of conditioning therapy;

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (1)

Xijing Hospital

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranous; Lupus Nephritis; Glomerulonephritis, IGA

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Shiren Sun, PhD

CONTACT

+86 17695670709; sunsrsun@163.com

Mingwei Jiang

CONTACT

+86 17695670709; 794480087@qq.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Nephrology

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: April 16, 2026
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

CN (1)