Clinical Trial of Blinatumomab in Refractory/Active Systemic Lupus Erythematosus in Children
The goal of this clinical trial is to learn if blinatumomab works to treat refractory or active systemic lupus erythematosus (SLE) in children and adults. It will also learn about the safety of blinatumomab. The main questions it aims to answer are: Does blinatumomab improve symptoms and disease activity in refractory/active SLE? What side effects or adverse events do participants experience when taking blinatumomab? Participants will: Receive two courses of blinatumomab injections over five consecutive days each Be monitored for 52 weeks to evaluate the treatment's safety and effectiveness Undergo regular blood tests and assessments of disease activity during follow-up visits Researchers will collect data on changes in serological markers, disease symptoms, and adverse events throughout the study.
∙ Participants must meet all the following criteria to be eligible for enrollment:
• Age: ≥ 5 years old.
• Diagnosis: Diagnosed with systemic lupus erythematosus (SLE) based on the 2019 EULAR/ACR classification criteria.
• Positive Antibody: At least one of the following antibodies positive within 12 months before screening or during the screening period:
‣ Antinuclear antibody (ANA) ≥ 1:80.
⁃ Anti-double-stranded DNA (anti-dsDNA) antibody above the upper limit of normal (ULN).
⁃ Anti-Smith (Anti-Sm) antibody above the ULN.
• Treatment Resistance: Inadequate response to at least three of the following:
‣ Oral corticosteroids (OCS),
⁃ Antimalarials,
⁃ Conventional immunosuppressants (e.g., cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide),
⁃ Biologics (e.g., TULIP-2, belimumab, rituximab). At least one treatment must involve immunosuppressants or biologics.
• SLEDAI-2000 Score: ≥ 6 based on the SLEDAI-2000 scoring system.
• Stable Standard Treatment: Currently receiving one or more of the following treatments at a stable dose:
‣ OCS (e.g., prednisone acetate or equivalent) at a stable dose for ≥7 days prior to initiation;
⁃ Antimalarials: Dose stable for at least 7 days prior to the first dose.
⁃ Conventional immunosuppressants: Stable dose for at least 4 weeks before screening and throughout the study.
• Laboratory Parameters:
‣ Absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L.
⁃ Peripheral CD19+ B cell count ≥ 25 cells/μL.
⁃ Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L.
⁃ Hemoglobin ≥ 80 g/L.
⁃ Platelet count ≥ 75 × 10⁹/L \*.
⁃ Left ventricular ejection fraction (LVEF) ≥ 55% with no significant ECG abnormalities.
⁃ Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m².
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; total bilirubin ≤ 2 × ULN.
⁃ No severe pulmonary lesions, SpO₂ ≥ 92%.
• Contraception: Female participants of childbearing potential must have a negative urine pregnancy test and agree to use effective contraception during the study and for 1 year after infusion.
• Informed Consent: The participant and their legal guardian must provide written informed consent, demonstrating understanding of the study objectives and willingness.
‣ Note: For SLE patients with thrombocytopenia below the inclusion threshold due to immune-related causes, and without active bleeding, investigators may use clinical discretion to determine eligibility.