This exploratory clinical trial aims to evaluate the efficacy and safety of Blinatumomab in treating children with calcineurin inhibitor (CNI)-resistant or multidrug-resistant steroid-resistant nephrotic syndrome (SRNS). Eligible participants include pediatric patients aged 2 to 17 years who have either failed to respond to adequate CNI therapy or are resistant to at least two classes of immunosuppressants, including CNIs and biologics. A short course of low-dose Blinatumomab will be administered in an open-label, single-arm, self-controlled trial design. The study seeks to determine whether Blinatumomab can reduce proteinuria and induce clinical remission in this difficult-to-treat population, offering a potential new therapeutic option for children with limited response to conventional therapies.
Nephrotic syndrome (NS) in children is characterized by excessive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Approximately 15-20% of pediatric NS cases are classified as steroid-resistant nephrotic syndrome (SRNS), a condition associated with poor prognosis and limited response to standard therapies. Calcineurin inhibitors (CNIs) are frequently used as first-line immunosuppressants in SRNS; however, a subset of patients demonstrate resistance to or intolerance of CNIs. Moreover, a proportion of patients may be refractory to multiple classes of immunosuppressive agents, including biologics, posing a significant therapeutic challenge. This exploratory, single-center, open-label clinical trial is designed to evaluate the safety and efficacy of Blinatumomab-a bispecific T-cell engager targeting CD19-positive B cells-in pediatric patients with CNI-resistant or multidrug-resistant SRNS. Eligible participants will include children aged 2 to 17 years who have either not responded to adequate CNI therapy or have failed to achieve remission despite treatment with at least two classes of immunosuppressive agents (including CNIs and biologics). A total of 6 patients will be enrolled and administered two short courses of low-dose Blinatumomab intravenously, each lasting 5 days. The primary efficacy outcome will be the rate of complete or partial remission of proteinuria. Secondary outcomes will include safety and tolerability assessments, changes in immunologic markers, and renal function monitoring. By selectively depleting CD19-positive B cells, Blinatumomab may modulate aberrant immune activation that underlies treatment-resistant SRNS. This study seeks to generate preliminary data on the potential therapeutic role of Blinatumomab in this difficult-to-treat pediatric population, with the ultimate goal of identifying a novel immunomodulatory approach for SRNS patients with limited treatment options.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Blinatumomab treatment for CNI-resistant/Intolerant pediatric steriod-resistant nephrotic syndrome Patients will receive two 5-day cycles of Blinatumomab (5 µg/m²/day, maximum dose 9 µg/day), administered intravenously. The second cycle will begin on the first day of the third week following the first cycle.
Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGEffectiveness and safety of Blinatumomab
Effectiveness: The primary endpoint is the proportion of patients achieving complete or partial remission within 24 weeks of treatment. Complete remission is defined as a urinary protein/creatinine ratio (UPCR) ≤ 200 mg/g for three consecutive days, while partial remission is defined as a ≥ 50% reduction in proteinuria from baseline with a UPCR between 200 and 2000 mg/g. Safety: Adverse events (AEs) and serious adverse events (SAEs) will be monitored and classified according to the CTCAE v5.0. This includes events such as cytokine release syndrome, fever, headache, and potential neurotoxicity.
Time frame: with 24 weeks of Blinatumomab treatment
long-term efficacy of Blinatumomab and Immunological Markers
Secondary Outcome Measures: Long-term Efficacy: Maintenance of remission at 52 weeks will be evaluated, along with the time to remission and the duration of remission. Immunological Markers: Changes in CD19+ B cell counts, particularly depletion and subsequent recovery of B cell populations, will be monitored. Recurrence of Disease: The time to first relapse and the proportion of patients who relapse during the 52week follow-up period will be analyzed.
Time frame: with 52 weeks of Blinatumomab
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