CD19-Directed Chimeric Antigen Receptor Autologous T Cells (CART19) for Lupus

CD19-Directed Chimeric Antigen Receptor Autologous T Cells (CART19) for Adolescents and Young Adults With Systemic Lupus Erythematosus (SLE)

This is a single-center, single-arm, open-label phase 1/2 study of CART19 in children and young adults with refractory Systemic lupus erythematosus (SLE), including both patients diagnosed with lupus nephritis (LN) and patients with non-renal Systemic lupus erythematosus (SLE).

Phase 1 will evaluate the safety of CART19 in 6-12 patients with Systemic lupus erythematosus (SLE). There is no planned dose escalation, but a dose de-escalation will be made based on the incidence of Dose Limiting Toxicities. Phase 2 will evaluate the efficacy and further evaluate the safety of CART19 in this population.

Study Overview

• Status: Recruiting
• Conditions: Cell Therapy; SLE; Systemic Lupus Erythematosus (SLE); Lupus; Lupus Nephritis (LN); CAR T Cell; CART19
• Intervention / Treatment: Biological: CART19

Detailed Description

Lupus disease activity is associated with increased numbers of activated naïve B cells and polyclonal expansion of antibody secreting cells, indicating a central role for B cells in the pathogenesis of SLE. While traditional anti-CD19 antibody therapies have been utilized with varying success in the treatment of Systemic lupus erythematosus (SLE), CD19 directed cellular therapies have emerged as an attractive therapeutic option that may lead to immunosuppression-free remission in this population given the ability of CD19 directed CAR T cells to more deeply deplete the B cell compartment. Previous clinical experience utilizing CD19 directed CAR T cells in patients diagnosed with Systemic lupus erythematosus (SLE) have exceeded any other Systemic lupus erythematosus (SLE) therapeutic available; although, those clinical trials have treated a limited number of subjects. During this trial the test article will be CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Caitlin Elgarten, MD; Phone Number: 267-425-7964; Email: elgartenc@chop.edu
• Study Contact Backup: Name: Melissa Varghese; Phone Number: 845-553-5358; Email: verghesem@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Melissa Varghese; Phone Number: 845-553-5358; Email: varghesem@chop.edu
      • Principal Investigator: Caitlin Elgarten, MD
      • Contact: Caitlin Elgarten, MD; Phone Number: 267-425-7964; Email: elgartenc@chop.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed informed consent form must be obtained prior to any study procedure. Labs or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required window.
2. Patient age must be 12-29 years, inclusive, at time of enrollment.
3. Meeting ACR/EULAR Classification Criteria for SLE
4. ANA positive > 1:80 and/or double-stranded DNA (dsDNA) positive

5. Active (refractory) disease, defined as follows:

   a. Lupus nephritis subjects must meet both the following criteria: i. ISN/RPS active nephritis Class III/IV +/- V lupus nephritis diagnosed by biopsy within past 12 months.

ii. Persistent and clinically significant: ≥2 measurements with urine protein with either of the following:

1. > 1mg/mg creatinine
2. > 0.5 mg/mg creatinine associated with renal dysfunction or low albumin.
3. > 0.5 mg/mg creatinine in a patient with rising proteinuria after prior complete renal response b. Non-renal SLE subjects must meet either of the following criteria: i. SLEDAI-2K ≥ 8 and clinical SLEDAI-2K ≥ 6 ii. Inability to decrease prednisone ≤7.5mg/day or 0.15mg/kg/day, whichever is lower, due to active disease.

6. Patients must have had at least 3 months of cumulative conventional therapy defined as:

1. Conventional induction immunosuppressive agent(s) (e.g., mycophenolate mofetil, cyclophosphamide), and
2. At least one additional therapy:

i. B-cell directed biologic therapy (e.g., rituximab, belimumab, ofatumumab, obinutuzumab) ii. Calcineurin inhibitor (e.g., tacrolimus, cyclosporine, voclosporin) iii. Other immunosuppressive medication for SLE (e.g., anifrolumab, abatacept, JAK inhibitor) 7. Adequate organ function status

1. Renal: eGFR must be ≥30 and subject cannot be receiving dialysis.
2. Hepatic: Transaminases < 5x upper limit of normal and serum conjugated (Direct) bilirubin <1.5x upper limit of normal unless attributable to SLE. If attributable to autoimmune disease, Child-Pugh score must be class A or class B. Child-Pugh score cannot be class C.
3. Cardiac: Shortening fraction > 28%, left ventricular ejection fraction >45%, and no evidence of severe pulmonary hypertension

4. Pulmonary: Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and <Grade 3 hypoxia; DLCO ≥40% (corrected for anemia and/or VA volume if necessary) if PFTs are clinically appropriate as determined by the treating investigator.

   8. Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria:

1. Active, untreated infections
2. HIV infection

3. Active Hepatitis B

   a. Patients must have a negative hepatitis B surface antigen to be enrolled on this study.

4. Active Hepatitis C
5. Patients with severe neuropsychiatric lupus or neurologic manifestations of SLE (e.g. stroke, seizure, psychosis, demyelinating syndromes, organic brain syndrome, or lupus related headaches)
6. Monogenic lupus (known)
7. Previous autologous or allogenic stem cell transplant
8. Previous kidney transplant
9. History of seizure disorder
10. Patients who are on anti-epileptic therapy
11. Participation in a clinical trial in which the patient receives an investigational drug within a time period equal or less than 5.5 half-lives of the investigational agent prior to study enrollment.
12. Subjects who are unwilling or unable to discontinue immunosuppressive medications at the times of CART19 infusion will be excluded from the trial
13. Any comorbidity that in the opinion of the investigators would jeopardize the ability of the subject to tolerate therapy.
14. Pregnant patients. All participants of childbearing potential must have negative pregnancy test.
15. Lactating participants who want to continue breastfeeding.
16. Patients who are unwilling to consent to LTFU

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: CART19; Participants will receive the study product. CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection.	Biological: CART19; CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of the dose limiting toxicities of CART19	Frequency of the dose limiting toxicities of CART19	up to 24 months post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of childhood SLE Clinical Remission off steroids (cCR-0) at 3 months		3 months post treatment
2-year overall survival rate		24 months post infusion
2-year flare free survival rate		up to 24 months post infusion
Feasibility of manufacturing CART19 for participants with SLE	Feasibility of manufacturing CART19 measured by the percentage of manufactured products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, or sterility	up to 24 months post infusion
Proportion of patients achieving a complete renal response	renal response will be measured by urine protein/creatinine ratio of < 0.5, normal renal function (serum creatinine ≤ULN) without worsening of baseline serum creatinine by more than 15%, and inactive urinary sediment (<10 red blood cells (RBCs)/high-power field (HPF) without RBC casts)	up to 24 months post infusion
Proportion of patients achieving a partial renal response	partial renal response will be measured by urine protein/creatinine ratio of < 0.5, normal renal function (serum creatinine ≤ULN) without worsening of baseline serum creatinine by more than 15%, and inactive urinary sediment (<10 red blood cells (RBCs)/high-power field (HPF) without RBC casts)	up to 24 months post infusion
Rate of CART19 expansion, persistence or B cell aplasia	Rate of CART19 expansion, persistence and B cell aplasia will be measured by qPCR and flow cytometry	up to 24 months post infusion
Survival of CART19 cells	CART19 cell survival will be measured by utilizing polymerase chain reaction analysis of whole blood to detect and quantify number of cells over time.	up to 24 months post infusion
Elevations in cytokines in serum	to assess bioreactivity and biological response following CART cell infusion, systemic soluble immune and inflammatory factors will be measured by assessing any change in elevations in cytokines in serum prior to infusion and after.	up to 24 months post infusion

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Caitlin Elgarten, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2025
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 17, 2025
• First Posted (Actual): February 21, 2025

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; CTL019 chimeric antigen receptor
• Other Study ID Numbers: 24-022668

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: Yes
• Studies a U.S. FDA-regulated device product: No