CAR T-cell therapy targeting CD19 for patients with refractory lupus

Safety/Phase I Study of PiggyBac Transposon Mediated Chimeric Antigen Receptor T Cells Targeting CD-19 in Thai Patients With Refractory Systemic Lupus Erythematosus

This study is testing a new CAR T-cell therapy to see if it can help adults with hard-to-treat lupus feel better and manage their symptoms.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Chulalongkorn University (Academic / other)
• Drugs / interventions: CAR T, CAR-T, cyclophosphamide, Fludarabine, Chimeric Antigen Receptor, chemotherapy
• Locations: 1 site (Bangkok, Please Select)
• Trial ID: NCT06150651 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial evaluates the safety and efficacy of PiggyBac transposon-mediated Chimeric Antigen Receptor (CAR) T-cells that target CD19 in adults with refractory Systemic Lupus Erythematosus (SLE). Participants will undergo a conditioning chemotherapy regimen followed by the infusion of CAR T-cells derived from their own blood. The study aims to assess treatment-related toxicity, changes in SLE disease activity, and the persistence of the CAR T-cells in the body over time. This is a single-institution study conducted at King Chulalongkorn Memorial Hospital in Bangkok.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 60 with a diagnosis of refractory Systemic Lupus Erythematosus.

Not a fit: Patients with mild or well-controlled lupus or those who have not exhausted standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with refractory lupus who have not responded to standard treatments.

How similar studies have performed: While CAR T-cell therapy has shown promise in other conditions, this specific approach targeting CD19 in refractory lupus is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 and 60 years.
2. Diagnosis of Systemic Lupus Erythematosus (SLE), as defined by the American College of Rheumatology (ACR) 1997 criteria, The Systemic Lupus International Collaborating Clinics (SLICC) criteria, or the European Alliance of Associations for Rheumatology (EULAR)/ACR classification.
3. Refractory SLE, defined by one or more of the following:

   3.1 Persistently active SLE requiring ongoing maintenance therapy (if not contraindicated) with:
   * Antimalarial drug.
   * Either mycophenolate (minimum daily dose of 1500 mg) or azathioprine (minimum daily dose of 1.5 mg/kg).
   * Patients must also need a minimum daily dose of 7.5 mg prednisolone for lower disease activity maintenance, or have a SLEDAI score of 8 or higher.

   3.2 Biopsy-proven proliferative lupus nephritis after two standard induction therapies, including intravenous cyclophosphamide (cumulative dose of at least 1.5 g) and mycophenolate mofetil (administered for a minimum of 3 months), unless contraindicated.

   3.3 Worsening of biopsy-proven lupus nephritis (activity index \> 6 and chronicity index \< 6 within 6 months), indicated by increased proteinuria and/or decreased estimated glomerular filtration rate, despite treatment with high-dose corticosteroids (prednisolone at least 0.7 mg/kg/day or equivalent) and either mycophenolate mofetil or cyclophosphamide for a minimum of 14 days.
4. Ability to understand and willingness to sign a written informed consent document.
5. Participants of child-bearing or child-fathering potential must agree to practice birth control from enrollment until four months after receiving CAR T-cell infusion.

Exclusion Criteria:

1. Pregnant or breastfeeding women.
2. History of active malignancy, excluding non-melanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast).
3. History of vital organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, cirrhosis, or psychiatric illness/social situations that limit compliance with study requirements.
5. Any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects or interfere with the research procedure, or the evaluation of safety and efficacy.
6. Serologic status indicating active HIV, hepatitis B, or C infection. Participants positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR prior to enrollment.
7. History of severe adverse drug reaction to Cyclophosphamide or Fludarabine.
8. Received a live vaccine within 30 days prior to CAR-T cell infusion.
9. eGFR CKD-EPI \< 30 ml/min/1.73m\^2.
10. Participation in other clinical investigations during the study period.
11. Prior receipt of CAR-T cell therapy outside this protocol.

Where this trial is running

Bangkok, Please Select

• King Chulalongkorn Memorial Hospital — Bangkok, Please Select, Thailand (Recruiting)

Study contacts

• Principal investigator: Wonngarm Kittanamongkolchai, MD — Chulalongkorn University
• Study coordinator: Wonngarm Kittanamongkolchai, MD

Conditions SLE