Anti-CD19 Chimeric Antigen Receptor T Cells for Refractory Systemic Lupus Erythematosus

NCT06585514 | Recruiting Phase 1 DMC

• 1 other identifier: BJGBYY-IIT-LCYJ-2024-040
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to evaluate the safety and efficacy of CD19 CAR T cells in the treatment of Systemic lupus erythematosus (SLE).

Conditions

Systemic Lupus Erythematosus (SLE); Lupus Nephritis (LN)

Keywords

Systemic Lupus Erythematosus (SLE); Lupus Nephritis (LN); CD19 CAR-T

Outcome Measures

Primary Outcomes (3)

• Phase I: Dose-limiting toxicity (DLT)

  The incidence and type of dose-limiting toxicity (DLT).

  28 days post infusion

• Phase I: Adverse events (AEs)

  The incidence and severity of adverse events (AE).

  30 days post infusion

• Phase II: Objective response rate (ORR)

  Proportions of subjects achieving SLE Responder Index (SRI)-4 response

  3 months and 6 months post infusion

Secondary Outcomes (6)

• Phase I: Objective response rate (ORR)

  3 months and 6 months

• Phase I: Long-term Adverse events (AEs)

  From 30 days after CD19 CAR T infusion to 2 years

• Phase I: Pharmacokinetics

  Up to 2 years post infusion

• Phase II: Adverse events (AEs)

  2 years post infusion

• Phase II: Pharmacokinetics

  Up to 2 years post infusion

Study Arms (1)

CD19 CAR

EXPERIMENTAL

Following the lymphodepleting treatment, patients will be treated with CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose.

Drug: CD19 CAR-T cells

Interventions

CD19 CAR-T cells DRUG

Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose.

CD19 CAR

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 3-65 years.
• Have a diagnosis of SLE and meet the classification criteria of 2019 European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
• Positive antinuclear antibody (ANA): ANA at a titer of ≥ 1:80 on Hep-2 cells or equivalent positive test (ever) and/or a positive anti-dsDNA serum antibody test (based on ELISA assay, ≥ 30 IU/mL).
• Refractory SLE and/or refractory lupus nephritis (LN):
• 4.1 Refractory SLE 4.1.1 Patients received at least 7.5 mg/kg/day of prednisolone to maintain low disease activity or the SLEDAI 2K score ≥8.
• Routine treatment is ineffective or the disease relapses after remission. Definition of routine treatment: use glucocorticoid (more than 1mg/kg/d) and cyclophosphamide for 6 months; and any of the following immunomodulatory drugs for more than 3 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents such as rituximab, belizumab, or telitacicept;
• 4.2 Refractory LN 4.2.1 Diagnosis of SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR), Biopsy-proven LN class III, IVa \[excluding III (C), IV-S (C) and IV-G (C)\] or, class V lupus nephritis combined with class III or IV, according to 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, see Appendix 3. Biopsy must be performed within 6 months before or during screening.
• Refractory lupus nephritis is defined as no induced remission to treatment regimens containing at least one immunosuppressant (including glucocorticoids, CTX, tacrolimus, MME, and cyclosporine) after 3 to 6 months, accompanied by no reduction (or worsening) of proteinuria or persistent antibody positives.
• CD19+ on B cells and continuous withdrawal of the immunosuppressive drugs for more than 1 week.
• The blood routine lymphocyte count of the subjects is \> 1 × 109/L, and there is no cell collection contraindication.
• No severe allergy.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2.
• Patients are expected to live for at least 90 days.
• Subjects and/or their guardian must understand and sign the informed consent.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Impaired consciousness or intracranial hypertension:
• Intracranial pressure elevation was above 15 mmHg;
• Organic encephalopathy syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis, visual impairment, and other brain lesions requiring intervention.
• Symptomatic congestive heart failure or severe cardiac arrhythmia:
• Previously documented left ventricular ejection fraction (LVEF) by echocardiography of \<45% in the 12 months;
• Abnormal electrocardiogram (ECG): left bundle branch block, bifascicular block or any clinically meaningful ECG abnormality;
• Congenital long QT syndrome or prolongation of the QT interval corrected for heart rate (QTcF) ≥ 470 ms. QTcF is calculated using Fridericia's Formula;
• Any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification;
• Unstable or poorly controlled angina pectoris, including the prinzmetal variant of angina pectoris;
• Myocardial infarction within 6 months.
• Manifestations of severe respiratory system failure:
• Hypoxemic respiratory failure: PaO2 \< 60 mmHg, PaCO2 \< 50 mmHg at sea level, resting and breathing air conditions;
• Subjects with pulmonary hypertension (PH): mean pulmonary artery pressure (mPAP) ≥25 mmHg measured by right heart catheterization (RHC);
• Subjects with hypercapnia (PaCO2 ≥ 50mmHg ) and/or ventilatory dysfunction (PH \<7.25 );

Sponsors & Collaborators

• Beijing GoBroad Hospital: lead

Study Sites (1)

Beijing GoBroad Hospital

Beijing, Beijing Municipality, 102206, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Tengyu Wang

CONTACT

18333186020; tengyu.wang@gohealtharo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Dept of Hemato-Oncology and Immunotherapy

Study Record Dates

• First Submitted: September 3, 2024
• First Posted: September 5, 2024
• Study Start: October 17, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)