CART19 treatment for lupus in young patients

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

This study is testing a new treatment called CART19 to see if it can help young people aged 12-29 with tough-to-treat lupus feel better and improve their health.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 12 Years to 29 Years
• Sex: All
• Sponsor: Children's Hospital of Philadelphia (other)
• Drugs / interventions: rituximab, belimumab, ofatumumab, obinutuzumab, anifrolumab, cyclophosphamide, prednisone, CAR T
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06839976 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of CART19, a CD19-directed chimeric antigen receptor T cell therapy, in children and young adults aged 12-29 with refractory Systemic Lupus Erythematosus (SLE). The study is divided into two phases: Phase 1 focuses on assessing safety in a small group of patients, while Phase 2 aims to further evaluate both safety and efficacy. The therapy targets B cells, which play a crucial role in the pathogenesis of SLE, potentially leading to deeper depletion of these cells and improved patient outcomes. Participants will receive CART19 cells administered via intravenous injection.

Who should consider this trial

Good fit: Ideal candidates for this study are children and young adults aged 12-29 with active, refractory Systemic Lupus Erythematosus who have not responded to conventional therapies.

Not a fit: Patients with mild or well-controlled lupus, or those outside the specified age range, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for young patients suffering from refractory lupus, potentially leading to remission without the need for immunosuppressive therapies.

How similar studies have performed: Previous clinical experiences with CD19-directed CAR T cells in SLE have shown promising results, indicating potential for success in this novel approach.

Eligibility criteria

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

Where this trial is running

Philadelphia, Pennsylvania

• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Caitlin Elgarten, MD — Children's Hospital of Philadelphia
• Study coordinator: Caitlin Elgarten, MD

Conditions: SLE, Systemic Lupus Erythematosus, CAR T Cell, CART19, Cell Therapy, Lupus, Lupus Nephritis