This is a single-arm, open-label, single-center, exploratory clinical trial evaluating the safety and efficacy of decitabine in male patients aged 1 month to 18 years with X-linked magnesium transporter 1 (MAGT1) deficiency. Eligible patients have a confirmed MAGT1 gene mutation leading to XMEN disease ( X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus (EBV) infection and N-linked glycosylation defect). The study will assess changes in liver function, immune function, and NKG2D expression, as well as adverse events, over four treatment cycles and the follow-up period.
Male participants aged 1 month to 18 years old.
Confirmed MAGT1 gene mutation by genetic testing.
Clinical manifestations consistent with XMEN disease, including liver dysfunction and/or EBV infection.
Reduced lymphocyte NKG2D expression.
Hypersensitivity to decitabine or any excipient.
Hematopoietic stem cell transplantation within 1 year before enrollment.
Severe concurrent organ dysfunction or systemic disease.
Positive HBsAg, anti-HCV, syphilis, or HIV test.
Single group
Decitabine
DrugDecitabine 20 mg/m² intravenous infusion once daily for 5 consecutive days every 4 weeks, for a total of 4 cycles.
Improvement magnitude of serum liver enzyme levels
Analyze serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (γ-GT) levels at key time points (before the second dose, before the fourth dose, 3 months after the last dose, and 6 months after the last dose) calculate the reduction magnitude from baseline (\[(baseline value-target time point value) / baseline value\] × 100%) at each time point, and evaluate the trend of liver function recovery.
Changes in NKG2D expression levels
Changes in NKG2D expression levels of peripheral blood lymphocytes from baseline; the expression levels were analyzed before the second administration, before the fourth administration, and 3 months after the last administration, and the absolute change values from baseline were calculated for each time point.
Cumulative incidence of grade ≥3 myelosuppression
Classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with observation periods covering the entire treatment duration (4 dosing cycles) and a 6-month follow-up period after the last dose. Criteria for determination: White blood cell count (WBC) \<1.0×10\^9/L or platelet count (PLT) \<25×10\^9/L in complete blood count (CBC). The proportion of patients meeting the above criteria was statistically analyzed.
Changes in TUSC3 expression in peripheral blood lymphocytes
Quantitative analysis of relative mRNA expression levels (using real-time fluorescent quantitative PCR) and protein expression levels (using Western blot) was performed to describe the upregulation/downregulation trends and relative change magnitudes at each key node (corresponding to primary endpoints) compared to baseline.
Increase in cytotoxic activity of NK cells/T cells
Cytotoxic function assays were used to detect cytotoxic activity (expressed as kill rate%), and the absolute increase values (target time point kill rate-baseline kill rate) at each key node (same as primary endpoint) were calculated compared to baseline.
Cumulative incidence of coagulation dysfunction
Prolonged prothrombin time (PT)\> 3 seconds, prolonged activated partial thromboplastin time (APTT)\> 10 seconds, or international normalized ratio (INR)\> 1.5 in coagulation function tests. The proportion of patients meeting any one of these criteria was statistically analyzed at each key node (corresponding to primary endpoints).
Overall incidence rate of adverse events and severity grading
The occurrence time, duration, severity (graded according to CTCAE version 5.0), and association with the study drug (definitively related, possibly related, or unrelated) of AE were recorded. The overall incidence rate and the composition ratio of AE at each severity level were statistically analyzed.
Occurrence of infection events
Infections are classified according to etiological detection results (EBV infection, bacterial infection, other infections), and the frequency, severity, and treatment outcomes of each type of infection are recorded.
Malignant tumor occurrence
The diagnosis time, pathological type, and clinical stage of newly developed malignant tumors will be recorded.
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Children's Hospital of Fudan University
Lead sponsor
National Natural Science Foundation of China
Collaborator
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