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

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.