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

Launched by CHILDREN'S HOSPITAL OF PHILADELPHIA · Feb 17, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment called CART19, which involves using specially modified immune cells to help children and young adults with Systemic Lupus Erythematosus (SLE) who have not responded well to standard treatments. SLE is an autoimmune condition where the body's immune system attacks its own tissues. The trial is focused on young people aged 12 to 29 and will assess the safety of CART19 in up to 12 participants. To qualify, patients must have a confirmed diagnosis of SLE, show signs of active disease despite at least three months of conventional therapy, and meet specific health criteria.

Participants in the trial can expect to receive CART19 therapy under close medical supervision. The study will first look at how safe the treatment is, and later on, it will also evaluate how effective it is in improving symptoms of lupus. It’s important to note that certain factors, like having active infections or specific health conditions, may prevent someone from participating. If eligible, individuals will need to sign a consent form and could potentially contribute to new insights that may help others with lupus in the future.

Gender

ALL

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, despite at least three months of conventional therapy, 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 on first morning sample with either of the following:
• • 1. \> 1000mg/g creatinine
• • 2. \> 500 mg/g creatinine associated with renal dysfunction or low albumin.
• • 3. \> 500 mg/g 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 conventional therapy defined as:
• • 1. Conventional induction immunosuppressive agent(s) (mycophenolate mofetil or 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, others) 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 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 negative hepatitis B surface antigen to be enrolled on this study.
• • 4. 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 'Patients who are on anti-epileptic therapy.
• • 10. 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.
• • 11. Use of concurrent immunosuppression
• • 1. Given the potential risks of additive immunosuppression and potentially deleterious effects of steroids, DMARDs and other biologics on the CART product, these medications are standardly discontinued prior to any cellular therapy. Subjects should be on stable doses of DMARDs for at least two weeks prior to enrollment. Subjects who are unwilling or unable to discontinue disallowed immunosuppressive medications at the times of T cell collection and CART19 infusion will be excluded from the trial.
• • 2. Disallowed immunosuppression includes any therapy (drugs, biologics or other treatments) clearly given for the purpose of treating the underlying autoimmune disease. This will include any FDA-approved or experimental agents not currently available but that become available during the period of the trial. Anti-malarial drugs for the treatment of SLE are permitted. The use of physiologic replacement hydrocortisone (or equivalent) or inhaled steroids is permitted.
• • 3. Immunosuppression for SLE treatment at times other than cell collection or at the time of infusion are permitted.
• • 12. Any comorbidity that in the opinion of the investigators would jeopardize the ability of the subject to tolerate therapy.
• • 13. Pregnant patients. All participants of childbearing potential must have negative pregnancy test.
• • 14. Lactating participants who want to continue breastfeeding.
• • 15. Patients who are unwilling to consent to LTFU