Allogeneic CD19/BCMA-Targeted CAR-γδT Cell Therapy: Safety and Preliminary Pharmacodynamics in Relapsed/Refractory Autoimmune Diseases

Safety and Preliminary Pharmacodynamics of Allogeneic CD19/BCMA-Targeted CAR-γδT Cell Therapy in Patients With Relapsed/Refractory Autoimmune Diseases

This study is a single-arm, intervention, dose-escalation clinical trial to evaluate the safety of allogeneic CD19/BCMA-targeted CAR-γδT cell in the treatment of relapsed/refractory autoimmune diseases

Study Overview

• Status: Not yet recruiting
• Conditions: Refractory/Relapsed Systemic Lupus Erythematosus; Refractory / Relapsed / Progressive Systemic Sclerosis; Refractory / Relapsing / Progressive Inflammatory Myopathy; Refractory / Relapsed Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis; Refractory / Relapsed Connective Tissue Disease-Associated Thrombocytopenia
• Intervention / Treatment: Biological: Allogeneic CD19/BCMA-targeted CAR-γδT cell injection; Drug: Cyclophosphamide; Drug: Fludarabine

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ying Wang; Phone Number: +86 15900225626; Email: wangying1@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years (including 18 years), no gender restrictions.
• Confirmed by flow cytometry to express CD19 or BCMA antigen on the surface of peripheral blood B cells.
• Major organ function must meet the following requirements (excluding abnormalities related to active autoimmune disease):
• Bone marrow function: Neutrophil count ≥ 1 × 10^9/L (no colony-stimulating factor therapy within 2 weeks prior to testing); Haemoglobin ≥ 60 g/L.
• Liver function: Alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN) (excluding ALT elevation due to inflammatory myopathy) ; Aspartate Aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN) (excluding AST elevation due to inflammatory myopathy); Total Bilirubin (TBIL) ≤ 2 times ULN (may be relaxed to ≤ 3.0 times ULN for subjects with Gilbert's syndrome).
• Renal function: Creatinine clearance (CrCl) ≥ 30 ml/min (calculated using the Cockcroft-Gault formula, excluding acute CrCl decline due to target disease; lupus nephritis (LN) patients excluded).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstain from sexual intercourse for at least 6 months during study treatment and for at least 6 months after study treatment completion.
• Voluntary participation in this clinical study, signing of informed consent, good compliance, and ability to complete follow-up.

Disease-specific inclusion criteria:

• Relapsed/refractory systemic lupus erythematosus
• Diagnosis of systemic lupus erythematosus (SLE) meeting the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
• Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000) ≥ 8 points; or significant organ involvement, such as lupus nephritis (histologically confirmed active nephritis of type III or IV, with or without type V involvement; National Institutes of Health [NIH] activity score > 2 points; evidence of elevated chronicity index; urine protein/creatinine ratio > 1.0 g/g, or 24-hour urine protein quantification > 1.0 g).
• Refractory or recurrent disease is defined as: no response after more than 6 months of conventional therapy, or recurrence of disease activity following remission. Conventional therapy is defined as: glucocorticoids combined with one or more of the following immunomodulatory agents: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab, belimumab, or tatalimab.
• Refractory/Recurrent/Progressive Systemic Sclerosis
• Scleroderma diagnosis conforms to the 2013 ACR（American College of Rheumatology） classification criteria.
• Positive for scleroderma-associated antibodies.
• Presence of diffuse cutaneous sclerosis or active interstitial lung disease (high-resolution computed tomography (HRCT) showing ground-glass opacities).
• Definition of recurrent/refractory: No response to conventional therapy for over 6 months, or recurrence following remission. Conventional therapy defined as: Glucocorticoids combined with any one or more of the following immunomodulators: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as belimumab, rituximab, or tocilizumab.
• Progressive definition: Rapid progression of cutaneous lesions (Modified Rodnan Skin Score (mRSS) increase > 25%); or progression of pulmonary lesions (Forced Vital Capacity (FVC) decline ≥10%, or FVC decline ≥5% accompanied by Diffusion Capacity for Carbon Monoxide (DLCO) decline ≥15%).

Note: Fulfilment of either criterion 4 or 5 is sufficient.

• Refractory/Recurrent/Progressive Inflammatory Myopathies
• Diagnosis of inflammatory myopathy conforms to the 2017 EULAR（European Alliance of Associations for Rheumatology）/ACR classification criteria (including dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), and necrotising myopathy (NM)).
• Muscle involvement present, Manual Muscle Test - 8 (MMT-8) score < 142 points, and at least 2 abnormalities in the following 5 core indicators: Physician Global Assessment (PhGA), Patient Global Assessment (PtGA) or extra-muscular disease activity score ≥ 2 points; Health Assessment Questionnaire (HAQ) total score ≥ 0.25 points; Muscle enzyme levels ≥1.5 times the upper limit of normal.
• Definition of recurrent/refractory: No response to conventional therapy for over 6 months, or relapse following remission. Conventional therapy defined as: Glucocorticoids combined with any one or more of the following immunomodulators: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as belimumab, rituximab, or tocilizumab.
• Definition of progressive disease: Rapid progression of interstitial lung disease within a short timeframe.

Note: Meeting any one criterion from either section 4 or 5 suffices.

• Refractory/Recurrent Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
• Diagnosis of ANCA-associated vasculitis conforms to the 2022 ACR/EULAR criteria, encompassing microscopic polyangiitis, granulomatous polyangiitis, and eosinophilic granulomatous polyangiitis.
• ANCA-associated antibody testing is positive (myeloperoxidase antibody [MPO-ANCA] or proteinase 3 antibody [PR3-ANCA] positive).
• Birmingham Vasculitis Activity Score (BVAS) ≥15 points (out of 63 total points), indicating active vasculitis.
• Refractory/recurrent definition: Failure to respond to conventional therapy for over 6 months, or recurrence following remission. Conventional therapy is defined as:Use of glucocorticoids in combination with any one or more of the following immunomodulatory agents: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as belimumab, rituximab, or tocilizumab.
• Refractory/Recurrent Connective Tissue Disease-Associated Thrombocytopenia
• Diagnosis of connective tissue disease conforming to the latest classification criteria, including but not limited to systemic lupus erythematosus, primary Sjögren's syndrome, antiphospholipid syndrome, and undifferentiated connective tissue disease.
• Diagnosed with connective tissue disease-associated thrombocytopenia, with platelet count < 30 × 10⁹/L, or platelet count < 50 × 10⁹/L accompanied by bleeding tendency.
• Bone marrow morphology consistent with features of immune thrombocytopenia.
• Previous treatment with at least one course of glucocorticoid pulse therapy, or high-dose glucocorticoids combined with one or more immunosuppressants (including biologics) for at least three months, failing to achieve partial remission or unable to maintain efficacy during glucocorticoid tapering.

Exclusion Criteria:

• -Individuals with a history of severe drug allergies or an allergic constitution.
• Presence or suspected presence of uncontrolled or treatable fungal, bacterial, viral, or other infections.
• Active, severe central nervous system disorders caused by autoimmune or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis).
• Patients with cardiac insufficiency.
• Patients with congenital immunoglobulin deficiency.
• History of malignant tumours within the past five years.
• End-stage renal disease (excluding lupus nephritis (LN) patients).
• Hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody (HBcAb) positive with peripheral blood hepatitis B virus (HBV) DNA > upper limit of normal; hepatitis C virus (HCV) antibody positive with peripheral blood hepatitis C virus (HCV) RNA positive; human immunodeficiency virus (HIV) antibody positive; positive syphilis test.
• Individuals with psychiatric disorders or severe cognitive impairment.
• Individuals who have previously received CAR-T therapy.
• Participants who have been enrolled in another clinical trial within the three months preceding study entry.
• Individuals who have received immunosuppressive agents or biological agents for therapeutic indications within five half-lives prior to study entry.
• Pregnant women or women planning pregnancy.
• Individuals deemed by the investigator to have other conditions rendering them unsuitable for inclusion in this study.

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: Patients with relapsed/refractory autoimmune diseases; A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by the investigational therapy: allogeneic CD19/BCMA-targeted CAR-γδT cells. Interventions: Biological: Allogeneic CD19/BCMA-targeted CAR-γδT cell injection Drug: Fludarabine Drug: Cyclophosphamide

Biological: Allogeneic CD19/BCMA-targeted CAR-γδT cell injection; Biological: Allogeneic CD19/BCMA-targeted CAR-γδT cell. Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine), patients will be treated with dose-escalation phase (3+3 design): Dose A (5 × 10^6 CAR+cells) ,Dose B(1 × 10^7 CAR+cells), Dose C (1.5 × 10^7 CAR+cells).; Drug: Cyclophosphamide; Eligible subjects will undergo lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises cyclophosphamide (300 mg/m² administered 3 days).; Drug: Fludarabine; Eligible subjects will undergo lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises fludarabine (30 mg/m² administered 3 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse Event	6 months
Incidence of Dose-Limiting Toxicities (DLTs)	First infusion date of allogeneic CD19/BCMA-targeted CAR-γδT cell to 28 days end cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK(Pharmacokinetics):Number and Copy Number of CD19/BCMA-targeted CAR-γδT cells	Number and copy number of CD19/BCMA-targeted CAR-γδT cells were assessed by number in peripheral blood. Blood samples were collected before and one year after cell infusion (until CD19/BCMA-targeted CAR-γδT cells were not detected for two consecutive times) to detect the number and copy number of CD19/BCMA-targeted CAR-γδT cells, and to evaluate the pharmacokinetics of CD19/BCMA-targeted CAR-γδT cells.	12 months
PK(Pharmacokinetics): Persistence of CD19/BCMA-targeted CAR-γδT cells	Persistence of CD19/BCMA -targeted CAR-γδT cells assessed by number in peripheral blood.	12 months
PD(Pharmacodynamics)：Peak Level of Cytokines in Serum	The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, interferon-γ（IFN-γ). Peak was defined as the maximum post-baseline level of the cytokine.	12 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: cell therapy; CD19/BCMA; CAR-γδT
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Systemic Vasculitis; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Lupus Erythematosus, Systemic; Recurrence; Scleroderma, Diffuse; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: IIT2026017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to the data underlying this study can be obtained from the corresponding author upon reasonable request and subject to any required ethical approvals.

Drug and device information, study documents

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