Systemic Lupus Erythematosus (SLE)
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALUniversal anti-CD70 CAR-T (CHT101)
Universal anti-CD70 CAR-T (CHT101) cell therpy
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Meet the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE). 2. SLEDAI-2000 score \>6. 3. Have at least one BILAG-2004 Grade A or two Grade B organ domain scores, or both. 4. Failure to respond to conventional therapy or disease relapse after remission. Conventional therapy: Glucocorticoids (≥1 mg/kg/day) combined with cyclophosphamide and ≥1 of the following immunosuppressants for \>6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine A, and/or biologics (e.g., rituximab, belimumab, telitacicept). 5. Aged 18-65 years; both genders eligible. 6. Adequate organ function:Bone marrow function: White blood cell count ≥3×10⁹/L. Absolute neutrophil count ≥1×10⁹/L (without colony-stimulating factor therapy within 2 weeks prior to testing). Hemoglobin ≥60 g/L; Liver function: Alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤3×ULN. Total bilirubin (TBIL) ≤1.5×ULN (except Gilbert's syndrome, TBIL ≤3.0×ULN); Renal function: Creatinine clearance (CrCl) ≥60 mL/min (calculated by Cockcroft-Gault formula); Coagulation: International normalized ratio (INR) ≤1.5×ULN. Prothrombin time (PT) ≤1.5×ULN; Cardiac function: Hemodynamic stability with left ventricular ejection fraction (LVEF) ≥55%. 7. Agrees to use double barrier methods, condoms, oral or injectable contraceptives, or intrauterine devices during the study period and for one year after taking the study medication. Females of childbearing potential must have a negative serum HCG test within 7 days prior to enrollment and must not be lactating. 8. Voluntarily participate in the study, provide written informed consent, and demonstrate good compliance with follow-up.
Exclusion criteria
1. Presence of neuropsychiatric lupus (NPSLE). 2. History of thrombotic thrombocytopenic purpura (TTP) or thrombotic microangiopathy (TMA). 3. History of severe drug allergies or hypersensitivity. 4. Active or suspected uncontrolled infections requiring treatment (including fungal, bacterial, viral, or other pathogens). 5. Central nervous system disorders caused by autoimmune diseases (ADs) or non-ADs. 6. Severe cardiac diseases. 7. Congenital immunoglobulin deficiency. 8. History of malignancy (except non-melanoma skin cancer, in situ cervical/bladder/breast/thyroid carcinoma with disease-free survival \>5 years). 9. End-stage renal failure. 10. Participants meeting any of the following: Hepatitis B surface antigen (HBsAg)-positive or hepatitis B core antibody (HBcAb)-positive with detectable HBV DNA; Hepatitis C virus (HCV) antibody-positive with detectable HCV RNA; HIV antibody-positive; Syphilis-positive (RPR and TPHA positive, or TPHA positive with RPR reconfirmed positive after 4 weeks). 11. Psychiatric disorders or severe cognitive impairment. 12. Participation in other clinical trials within 3 months prior to enrollment. 13. Pregnant women or those planning pregnancy. 14. Other conditions deemed by the investigator to preclude study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SRI-4 Response | SRI-4 response assessed at Month 3 after CHT101 infusion. | 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). |
| Safety Evaluation | safety evaluation Within 12 months after CHT101 infusion. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DORIS remission | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | 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. |
| Lupus Low Disease Activity State (LLDAS) remission | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | 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. |
| Overall Renal Response (ORR) | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion | Evaluated only in participants with lupus nephritis, encompassing those achieving either complete renal response (CRR) or partial renal response (PRR). |
| Complete Renal Response (CRR) | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | 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. |
| Partial Renal Response (PRR) | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | 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. |
| Primary Efficacy Renal Response (PERR) | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | 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. |
| BILAG 2004 | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | The absence of new organ Class A scores or two organ Class B scores indicates improvement. |
| Overall assessment of physicians | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | The mitigation indicator was a baseline increase of less than 0.3 on a 3-point scale. |
| Organ Damage | At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion. | The score was based on the SLE International Cooperation Group Injury Index (SDI). The higher the index, the worse the prognosis. |
Countries
China
Contacts
CONTACTXiaojun Tang
STUDY_CHAIRLingyun Sun
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Outcome results
None listed