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

NCT06710717 | Recruiting Phase 1 DMC

• 1 other identifier: JEP-2024-754
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Lupus Erythematous (SLE)

Keywords

CAR T cells; SLE; treatment-refractory; severe SLE

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Clinical Response Rate

  Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion

• Rate of B cell aplasia

  Months 1, 3, 6, 9, 12, 15, 18, 21, 24 after CAR-T cells infusion

• Rate of Immunological response

  Months 1, 3, 6, 9, 12, 15, 18, 21, 24 after CAR-T cells infusion

• Mean of Quality of life score

  Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion

Study Arms (1)

autologous CD19 CAR T-cells

EXPERIMENTAL

Single Infusion of autologous CD19 CAR T- cells

Biological: CD19 CAR-T cells

Interventions

CD19 CAR-T cells BIOLOGICAL

Study participant will be given single infusion of autologous CD19 CAR-T cells following lymphodepletion chemotherapy

autologous CD19 CAR T-cells

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University of Malaysia: lead
• Plutonet Sdn Bhd: collaborator

Study Sites (1)

University Kebangsaan Malaysia Medical Center

Bandar Tun Razak, Kuala Lumpur, 56000, Malaysia

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

S Fadilah Abdul Wahid, PhD

CONTACT

+60391456450; sfadilah@hctm.ukm.edu.my

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: November 21, 2024
• First Posted: November 29, 2024
• Study Start: January 3, 2025
• Primary Completion (Estimated): December 2, 2028
• Study Completion (Estimated): January 2, 2029
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)