Autologous CD19 Car T-Cell Therapy For Severe Refractory Systemic Lupus Erythematosus (SLE)

Autologous CD19 Car T-Cell Therapy For Patients With Severe Refractory Systemic Lupus Erythematosus - A Pilot Study

This pilot clinical study aims to evaluate the effectiveness of Chimeric Antigen Receptor (CAR) T-cell therapy in treating severe, refractory systemic lupus erythematosus (SLE), an autoimmune disease driven by autoreactive B-cells. Current treatments for severe SLE, including glucocorticoids, cytotoxic, and immunosuppressive drugs, have significant limitations. These treatments do not adequately control the underlying autoimmune process and require long-term use, leading to chronic side effects and often failing to prevent permanent organ damage. Given the high prevalence and mortality rates associated with SLE in regions like Asia and Malaysia, there is a pressing need for more effective therapies.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematous (SLE)
• Intervention / Treatment: Biological: CD19 CAR-T cells

Detailed Description

This study seeks to investigate CAR-T cell therapy's potential for treating severe treatment-refractory systemic lupus erythematosus (SLE) in Malaysian patients.

STUDY OBJECTIVES

General Objective: To evaluate the safety and efficacy of autologous CD19 CAR T-cell infusion in patients with severe refractory SLE.

Specific Objectives:

To evaluate the safety and tolerability of treatment. To evaluate efficacy as measured by response rates and survival. To evaluate the quality of life based on the use of validated health questionnaire tools.

Hypothesis:

Intravenous autologous CD19 CAR T-cell therapy is safe, and efficacious in patients with severe refractory SLE.

EXPECTED OUTCOME OF THE STUDY:

CD19 CAR T-cell therapy is expected to result in:

Clinical remission as assessed by DORIS remission) with a good safety profile Serologic remission (defined as negative anti-dsDNA and normal complement C3 and C4 levels) at 3 months Sustained DORIS remission for at least 12 months Improvement in organ function Prolongation of duration of drug-free remission Improvement in quality of life Manageable adverse effects

STUDY POPULATION This pilot study will be conducted between 2025 and 2028 involving 5 patients diagnosed with severe, treatment-refractory SLE. Eligibility criteria were based on previously published studies and international guidelines for CAR treatment for patients with autoimmune disease (Boulougoura et al., 2023).

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: S Fadilah Abdul Wahid, PhD; Phone Number: +60391456450; Email: sfadilah@hctm.ukm.edu.my

Study Locations

• Malaysia
  • Wilayah Persekutuan Kuala Lumpur
    • Bandar Tun Razak, Wilayah Persekutuan Kuala Lumpur, Malaysia, 56000
      • Recruiting
      • University Kebangsaan Malaysia Medical Center
      • Contact: S Fadilah Abdul Wahid, PhD; Phone Number: +60391456450; Email: sfadilah@hctm.ukm.edu.my

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

-

Aged between ≥ 18 to ≤ 65 years Clinical Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria (Fanouriakis et al., 2019) Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history Active disease (defined by not being in remission according to DORIS criteria or in a low disease activity state [LLDAS]) (Franklyn et al., 2016, van Vollenhoven et al., 2021) With at least one active organ system involvement Persistent active disease with insufficient response to glucocorticoids and at least 2 of the following treatments for at least 3 months each: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus or voclosporin.

Serum ALT <5 times the normal value, serum bilirubin <3 times the normal value, Left ventricular ejection fraction >45% Life expectancy of more than 3 months Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Psychological, sociological or geographical conditions precluding compliance A female of childbearing age must have a negative pregnancy test and is on two effective contraception methods A male must use two effective contraception methods

Exclusion Criteria:

-

Active cancer or receiving cancer treatment Evidence of severe lung, FVC <45% and/or DLCO (corrected for Hb) <30% predicted, heart (NYHA class III/IV, arrhythmia, AV block, uncontrolled hypertension), liver failure or severe neurologic disorders.

Pre-existing irreversible kidney damage and creatinine clearance below 30 ml/min ( to review) Severe pancytopenia HIV positivity. Active Hepatitis B, C infection. Septicemia. Pregnant/nursing female. Receiving stem cell transplant within 12 weeks of enrolment, chemotherapy or radiotherapy within 8 weeks of enrolment Active CNS involvement.

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: autologous CD19 CAR T-cells; Single Infusion of autologous CD19 CAR T- cells	Biological: CD19 CAR-T cells; Study participant will be given single infusion of autologous CD19 CAR-T cells following lymphodepletion chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Adverse events	Incidence of adverse event (AE), classified according to CTCAE version 5.0, and evaluation and classification of Cytokine Release Syndrome (CRS) and Immune Effector cell-associated Neurotoxicity Syndrome (ICANS)	Starting form day 0 up to 24 months after CAR-T cells infusion
SLEDAI Remission Rate	Remission is evaluated by fulfilment of SLEDAI remission criteria	Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response Rate	Measured by BILAG, PGA, SLICC/ACR	Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion
Rate of B cell aplasia	Numbers of B cells in peripheral blood measured by flow cytometry	Months 1, 3, 6, 9, 12, 15, 18, 21, 24 after CAR-T cells infusion
Rate of Immunological response	Changes in the levels of SLE-associated serum autoantibodies	Months 1, 3, 6, 9, 12, 15, 18, 21, 24 after CAR-T cells infusion
Mean of Quality of life score	Quality of life Assessed by FACIT-F	Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Collaborators: Plutonet Sdn Bhd

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2025
• Primary Completion (Estimated): December 2, 2028
• Study Completion (Estimated): January 2, 2029

Study Registration Dates

• First Submitted: November 21, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: SLE; CAR T cells; treatment-refractory; severe SLE
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: JEP-2024-754

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
• product manufactured in and exported from the U.S.: No