Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06150651
Other study ID # SLE-PB-CD19-CART
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date December 1, 2023
Est. completion date November 30, 2025

Study information

Verified date February 2024
Source Chulalongkorn University
Contact Wonngarm Kittanamongkolchai, MD
Phone 66875995974
Email wonngarm.k@gmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

A Phase 1 clinical trial to evaluate the safety and efficacy of PiggyBac transposon-mediated Chimeric Antigen Receptor(CAR) T-cells targeting CD19 in refractory Systemic Lupus Erythematosus (SLE) patients who have not responded to standard immunosuppressive treatments.


Description:

This is a single-institution phase I study in adults with refractory SLE. Autologous Peripheral Blood Mononuclear Cells will be transduced with a chimeric antigen receptor targeting the B-cell surface antigen CD19 using the PiggyBac Transposon system. Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide, followed by the infusion of 1x10^6 cells/kg CD-19 CAR T-cells. Subjects will be evaluated post-treatment for toxicity, SLE disease activity, and the persistence of CAR-expressing T cells in vivo.


Recruitment information / eligibility

Status Recruiting
Enrollment 6
Est. completion date November 30, 2025
Est. primary completion date November 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 60 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Other:
CAR T-cell therapy
1x10^6 cells/kg CD-19 CAR-T cells

Locations

Country Name City State
Thailand King Chulalongkorn Memorial Hospital Bangkok Please Select

Sponsors (3)

Lead Sponsor Collaborator
Chulalongkorn University Health Systems Research Institute, King Chulalongkorn Memorial Hospital

Country where clinical trial is conducted

Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety of PiggyBac transposon-mediated CAR T-cell infusion targeting CD19 in adult patients with refractory SLE. The incidence of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 Up to 28 days after CD-19 CAR-T cell infusion
Secondary Disease activity of SLE The Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 3, 6, and 12 months after CD-19 CAR-T cell infusion
Secondary Complete response rate of lupus nephritis Complete response defined as normal or = 25% decline of estimated glomerular filtration rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) from baseline and urinary protein to creatinine index (UPCI) or 24-hour urinary protein = 0.5 g/g or g/day 3, 6, and 12 months after CD-19 CAR-T cell infusion
Secondary Partial response rate of lupus nephritis Partial response defined as normal or =25% decline of eGFR CKD-EPI from baseline and at least 50% reduction of proteinuria, with a UPCI or 24-hour urinary protein between 0.5 to 3 g/g or g/day 3, 6, and 12 months after CD-19 CAR-T cell infusion
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06063668 - Autotaxin as Abiomarker in Systemic Lupus Erythematosus Patients
Completed NCT05624437 - BElimumab corticoSteroids Sparing Treatment in Systemic Lupus Erythematosus
Recruiting NCT06445127 - Evaluation of Patients With Lupus Nephritis Using Kidney MRI (Magnetic Resonance Imaging) N/A
Recruiting NCT04866615 - Posterior Segment Evaluation of Patients With SLE Using OCT and OCTA
Not yet recruiting NCT04645225 - Clinical Characteristic and MEFV Gene Mutations in Patient With Juvenile Onest Systemic Lupus Erythematosus
Recruiting NCT04604990 - National Systemic Lupus Erythematosus Prospective Cohort, Saudi Arabia
Recruiting NCT06056921 - Safety and Efficacy of CD19 Targeted CAR-T Therapy for Refractory Autoimmune Disease Phase 1
Recruiting NCT06294236 - Study Evaluating SC291 in Subjects With Severe r/r B-cell Mediated Autoimmune Diseases (GLEAM) Phase 1
Recruiting NCT05866861 - A Study in Participants With Mild-to-moderate Systemic Lupus Erythematosus Phase 1