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

NCT07490275 | Not Yet Recruiting Phase 1

• 1 other identifier: IIT2026017
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

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

Keywords

CD19/BCMA; CAR-γδT; cell therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• PK(Pharmacokinetics):Number and Copy Number of CD19/BCMA-targeted CAR-γδT cells

  12 months

• PK(Pharmacokinetics): Persistence of CD19/BCMA-targeted CAR-γδT cells

  12 months

• PD(Pharmacodynamics)：Peak Level of Cytokines in Serum

  12 months

Study Arms (1)

Patients with relapsed/refractory autoimmune diseases

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Allogeneic CD19/BCMA-targeted CAR-γδT cell injection BIOLOGICAL

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).

Patients with relapsed/refractory autoimmune diseases

Cyclophosphamide DRUG

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).

Patients with relapsed/refractory autoimmune diseases

Fludarabine DRUG

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).

Patients with relapsed/refractory autoimmune diseases

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Scleroderma, Diffuse; Recurrence; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Scleroderma, Systemic; Skin Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Ying Wang

CONTACT

+86 15900225626; wangying1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: March 24, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share