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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection.
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
RECRUITINGFrequency of the dose limiting toxicities of CART19
Frequency of the dose limiting toxicities of CART19
Time frame: up to 24 months post infusion
Rate of childhood SLE Clinical Remission off steroids (cCR-0) at 3 months
Time frame: 3 months post treatment
2-year overall survival rate
Time frame: 24 months post infusion
2-year flare free survival rate
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: up to 24 months post infusion
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