Phase
Condition
Lupus
Lupus Nephritis
Cutaneous Lupus Erythematosus
Treatment
CART19
Clinical Study ID
Ages 12-29 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Signed informed consent form must be obtained prior to any study procedure. Labs orother procedures obtained during routine clinical care may be used for eligibilityif obtained within the protocol required window.
Patient age must be 12-29 years, inclusive, at time of enrollment.
Meeting ACR/EULAR Classification Criteria for SLE
ANA positive > 1:80 and/or double-stranded DNA (dsDNA) positive
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 activenephritis Class III/IV +/- V lupus nephritis diagnosed by biopsy within past 12months.
ii. Persistent and clinically significant: ≥2 measurements with urine protein on first morning sample with either of the following:
> 1000mg/g creatinine
> 500 mg/g creatinine associated with renal dysfunction or low albumin.
> 500 mg/g creatinine in a patient with rising proteinuria after prior completerenal 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.
Patients must have had at least 3 months conventional therapy defined as:
Conventional induction immunosuppressive agent(s) (mycophenolate mofetil orcyclophosphamide), and
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
Renal: eGFR must be ≥30 and subject cannot be receiving dialysis.
Hepatic: Transaminases < 5x upper limit of normal and serum conjugated (Direct)bilirubin <1.5x upper limit of normal unless attributable to SLE. If attributable toautoimmune disease, Child-Pugh score must be class A or class B. Child-Pugh scorecannot be class C.
Cardiac: Shortening fraction > 28%, left ventricular ejection fraction >45%, and noevidence of severe pulmonary hypertension
Pulmonary: Must have a minimum level of pulmonary reserve defined as ≤ Grade 1dyspnea and <Grade 3 hypoxia; DLCO ≥40% (corrected for anemia and/or VA volume) ifPFTs are clinically appropriate as determined by the treating investigator.
Subjects of reproductive potential must agree to use acceptable birth controlmethods.
Exclusion
Exclusion Criteria:
Active, untreated infections
HIV infection
Active Hepatitis B a. Patients must have negative hepatitis B surface antigen to be enrolled on thisstudy.
Hepatitis C
Patients with severe neuropsychiatric lupus or neurologic manifestations of SLE (e.g. stroke, seizure, psychosis, demyelinating syndromes, organic brain syndrome,or lupus related headaches)
Monogenic lupus (known)
Previous autologous or allogenic stem cell transplant
Previous kidney transplant
History of seizure disorder 'Patients who are on anti-epileptic therapy.
Participation in a clinical trial in which the patient receives an investigationaldrug within a time period equal or less than 5.5 half-lives of the investigationalagent prior to study enrollment.
Use of concurrent immunosuppression
Given the potential risks of additive immunosuppression and potentiallydeleterious effects of steroids, DMARDs and other biologics on the CARTproduct, these medications are standardly discontinued prior to any cellulartherapy. Subjects should be on stable doses of DMARDs for at least two weeksprior to enrollment. Subjects who are unwilling or unable to discontinuedisallowed immunosuppressive medications at the times of T cell collection andCART19 infusion will be excluded from the trial.
Disallowed immunosuppression includes any therapy (drugs, biologics or othertreatments) clearly given for the purpose of treating the underlying autoimmunedisease. This will include any FDA-approved or experimental agents notcurrently available but that become available during the period of the trial.Anti-malarial drugs for the treatment of SLE are permitted. The use ofphysiologic replacement hydrocortisone (or equivalent) or inhaled steroids ispermitted.
Immunosuppression for SLE treatment at times other than cell collection or atthe time of infusion are permitted.
Any comorbidity that in the opinion of the investigators would jeopardize theability of the subject to tolerate therapy.
Pregnant patients. All participants of childbearing potential must have negativepregnancy test.
Lactating participants who want to continue breastfeeding.
Patients who are unwilling to consent to LTFU
Study Design
Study Description
Connect with a study center
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United StatesActive - Recruiting
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