Universal Anti-CD70 CAR-T (CHT101) Cell Therapy for Relapsed Refractory Systemic Lupus Erythematosus

Official title

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

Overview

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

• Biological Universal anti-CD70 CAR-T (CHT101)
  Universal anti-CD70 CAR-T (CHT101) cell therpy

Primary outcome measures

• SRI-4 Response [Time frame: SRI-4 response assessed at Month 3 after CHT101 infusion.]
• Safety Evaluation [Time frame: safety evaluation Within 12 months after CHT101 infusion.]

Secondary outcome measures (9)

• DORIS remission [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• Lupus Low Disease Activity State (LLDAS) remission [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• Overall Renal Response (ORR) [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion]
• Complete Renal Response (CRR) [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• Partial Renal Response (PRR) [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• Primary Efficacy Renal Response (PERR) [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• BILAG 2004 [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• Overall assessment of physicians [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]
• Organ Damage [Time frame: At 1 month, 2 month, 3 month, 6 month, 9 month, 12month after CHT101 infusion.]

Eligibility criteria

Inclusion criteria

• Meet the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE).
• SLEDAI-2000 score >6.
• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School — Nanjing

Identifiers

NCT: NCT06946485 · CHT101AIIT-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗