This investigator-initiated trial aims to evaluate the safety and efficacy of universal anti-CD70 CAR-T (CHT101) in patients with relapsed refractory systemic lupus erythematosus.
This study is a non-randomized, open-label, single-arm clinical trial designed to assess the efficacy and safety of universal anti-CD70 CAR-T (CHT101) in patients with relapsed refractory systemic lupus erythematosus.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Universal anti-CD70 CAR-T (CHT101) cell therpy
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, China
RECRUITINGSRI-4 Response
SRI-4 Response defined as a decrease of ≥4 points from baseline in the SELENA-SLEDAI score, no new BILAG-evaluated grade A organs or \<2 BILAG-evaluated grade B organs from baseline, and no deterioration in the physician's overall assessment (an increase of \<0.30 points from baseline).
Time frame: SRI-4 response at 1 month after CHT101 infusion.
Safety Evaluation
Safety evaluation includes the collection of adverse events (AE), serious adverse events (SAE), vital signs and physical examinations, laboratory tests, including pregnancy tests and concomitant treatments. Safety is evaluated using the NCI-CTCAE 5.0 standard. CRS is evaluated using the ASTCT Consensus Grading Criteria, ICANS is evaluated using the Adult ASTCT ICANS Consensus Grading Criteria, acute GVHD is evaluated using the 2016 Mount Sinai Acute GVHD International Consortium Grading Criteria, and chronic GVHD is evaluated using the 2020 NCCN Hematopoietic Cell Transplantation Clinical Practice Guidelines, Version 1.0.
Time frame: safety evaluation Within 12 months after CHT101 infusion.
DORIS remission
The remission of SLE was based on the DORIS 2021 criteria, namely: SLEDAI=0 and PGA \< 0.5 (0-3 points), serology was not considered, and patients could use antimalarial drugs, low-dose glucocorticoids (prednisolone ≤5mg/ day), and/or immunosuppressants including biologics.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
Lupus Low Disease Activity State (LLDAS) remission
requiring simultaneous fulfillment of all the following criteria: * SLEDAI-2K score ≤4, with no active involvement of major organs (kidneys, central nervous system, heart/lungs, gastrointestinal tract, vasculitis, or fever); * PGA score ≤1; * No new lupus-related symptoms; * Maintenance dose of prednisone (or equivalent) ≤7.5 mg/day.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
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Overall Renal Response (ORR)
Evaluated only in participants with lupus nephritis, encompassing those achieving either complete renal response (CRR) or partial renal response (PRR).
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion
Complete Renal Response (CRR)
Evaluated only in participants with lupus nephritis; participants meeting all the following criteria are considered to have achieved CRR: * Urinary protein excretion \<0.5 g/24 h or urine protein-to-creatinine ratio (UPCR) \<0.5 g/g; * Estimated glomerular filtration rate (eGFR) decline ≤10-15% from baseline or eGFR ≥60 mL/min/1.73 m²; * No use of rescue medications exceeding protocol-specified thresholds prior to assessment.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
Partial Renal Response (PRR)
Evaluated only in participants with lupus nephritis; participants meeting all the following criteria are considered to have achieved PRR: * eGFR decline ≤10-15% from baseline or eGFR ≥60 mL/min/1.73 m²; * Improvement in 24-hour UPCR: * For participants with baseline UPCR ≤3.0 g/g: UPCR \<1.0 g/g; * For participants with baseline UPCR \>3.0 g/g: \>50% reduction from baseline and UPCR \<3.0 g/g; * No use of rescue medications exceeding protocol-specified thresholds prior to assessment.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
Primary Efficacy Renal Response (PERR)
Evaluated only in participants with lupus nephritis; participants meeting all the following criteria are considered to have achieved PERR: * UPCR ≤0.7 g/g; * eGFR decline ≤20% from baseline or eGFR ≥60 mL/min/1.73 m²; * No use of rescue medications exceeding protocol-specified thresholds prior to assessment.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
BILAG 2004
The absence of new organ Class A scores or two organ Class B scores indicates improvement.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
Overall assessment of physicians
The mitigation indicator was a baseline increase of less than 0.3 on a 3-point scale.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.
Organ Damage
The score was based on the SLE International Cooperation Group Injury Index (SDI). The higher the index, the worse the prognosis.
Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.