A Clinical Study of the Safety and Efficacy of Universal Anti-CD70 CAR-T (CHT101) for the Treatment of Relapsed and Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- SRI-4 Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE).
- •SLEDAI-2000 score >
- •Have at least one BILAG-2004 Grade A or two Grade B organ domain scores, or both.
- •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).
- •Aged 18-65 years; both genders eligible.
- •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%.
- •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.
- •Voluntarily participate in the study, provide written informed consent, and demonstrate good compliance with follow-up.
排除标准
- •Presence of neuropsychiatric lupus (NPSLE).
- •History of thrombotic thrombocytopenic purpura (TTP) or thrombotic microangiopathy (TMA).
- •History of severe drug allergies or hypersensitivity.
- •Active or suspected uncontrolled infections requiring treatment (including fungal, bacterial, viral, or other pathogens).
- •Central nervous system disorders caused by autoimmune diseases (ADs) or non-ADs.
- •Severe cardiac diseases.
- •Congenital immunoglobulin deficiency.
- •History of malignancy (except non-melanoma skin cancer, in situ cervical/bladder/breast/thyroid carcinoma with disease-free survival >5 years).
- •End-stage renal failure.
- •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).
- •Psychiatric disorders or severe cognitive impairment.
- •Participation in other clinical trials within 3 months prior to enrollment.
- •Pregnant women or those planning pregnancy.
- •Other conditions deemed by the investigator to preclude study participation.
研究组 & 干预措施
Universal anti-CD70 CAR-T (CHT101)
干预措施: Universal anti-CD70 CAR-T (CHT101) (Biological)
结局指标
主要结局
SRI-4 Response
时间窗: 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).
SRI-4 Response
时间窗: SRI-4 response at 1 month 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
时间窗: 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.
次要结局
- DORIS remission(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Lupus Low Disease Activity State (LLDAS) remission(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Overall Renal Response (ORR)(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion)
- Complete Renal Response (CRR)(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Partial Renal Response (PRR)(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Primary Efficacy Renal Response (PERR)(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Disease Activity Index(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Organ Damage(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- BILAG 2004(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)
- Overall assessment of physicians(At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.)