Evaluating the Safety and Efficacy of Decitabine in the Treatment of XMEN Patients

Single-arm Clinical Study Evaluating the Safety and Efficacy of Decitabine in the Treatment of X-linked MAGT1 Deficiency With Increased Susceptibility to EBV Infection and N-linked Glycosylation Defect (XMEN) Patients

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.

Study Overview

• Status: Not yet recruiting
• Conditions: MAGT1 Deficiency
• Intervention / Treatment: Drug: Decitabine

Detailed Description

XMEN disease is a rare X-linked primary immunodeficiency caused by loss-of-function mutations in MAGT1, leading to chronic Epstein-Barr virus (EBV) infection, liver dysfunction, and reduced NKG2D expression on lymphocytes. TUSC3 shares functional redundancy with MAGT1 but is epigenetically silenced in immune and liver tissues. Decitabine, a DNA methyltransferase inhibitor, can reactivate TUSC3 expression.

This single-arm, open-label, single-center study will enroll six male participants aged 1 month to 18 years with genetically confirmed MAGT1 mutation and a clinically diagnosis of XMEN disease. Eligible participants will receive decitabine intravenously at 20 mg/m² once daily for five consecutive days every four weeks, for a total of four cycles. Safety and efficacy will be evaluated by monitoring NKG2D expression, liver enzymes levels, EBV viral load, lymphocyte function, TUSC3 expression, and adverse events. Participants will be followed for 180 days after the last dose.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jia Hou, Ph.D., M.D.; Phone Number: 86-21-64933338; Email: doctorhoujia@hotmail.com
• Study Contact Backup: Name: Wenjie Wang, M.D.; Phone Number: 86-21-64931085; Email: amazingmm@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University
      • Contact: Jia Hou, Ph.D., M.D.; Phone Number: 86-21-64933338; Email: doctorhoujia@hotmail.com
      • Contact: Wenjie Wang, M.D.; Phone Number: 86-21-64931085; Email: amazingmm@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male participants aged 1 month to 18 years old.
2. Confirmed MAGT1 gene mutation by genetic testing.
3. Clinical manifestations consistent with XMEN disease, including liver dysfunction and/or EBV infection.
4. Reduced lymphocyte NKG2D expression.
5. Vital signs within normal range at screening.
6. Expected survival ≥ 6 months.
7. Able to comply with study procedures.
8. Guardian and participant provide written informed consent.

Exclusion Criteria:

1. Hypersensitivity to decitabine or any excipient.
2. Hematopoietic stem cell transplantation within 1 year before enrollment.
3. Severe concurrent organ dysfunction or systemic disease.
4. Positive HBsAg, anti-HCV, syphilis, or HIV test.
5. Neurological or psychiatric disorders that impair compliance.
6. Participation in another clinical trial within 3 months.
7. Other conditions judged inappropriate by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Decitabine, Route of administration: Intravenous infusion; Participants receive decitabine at a dose of 20 mg/m² once daily for five consecutive days per treatment cycle. Each dose is administered as a continuous intravenous infusion over at least one hour. Each cycle consists of five doses, and a total of four cycles are planned.	Drug: Decitabine; Decitabine 20 mg/m² intravenous infusion once daily for 5 consecutive days every 4 weeks, for a total of 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6 months after the last dose
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.	up to 6 months after the last dose
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.	up to 6-month follow-up period after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6-month after the last dose
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.	up to 6 months after the last dose
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).	up to 6 months after the last dose
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.	up to 6 months after the last dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6 months after the last dose
Malignant tumor occurrence	The diagnosis time, pathological type, and clinical stage of newly developed malignant tumors will be recorded.	up to 6 months after the last dose

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: Jia Hou, Ph.D., M.D., Children's Hospital of Fudan University

Publications and helpful links

General Publications

• Ding H, Li Y, Fang M, Chen J, Liu L, Lu Z, Hou J, Luo M. Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. J Allergy Clin Immunol. 2023 Jun;151(6):1622-1633.e10. doi: 10.1016/j.jaci.2023.04.003. Epub 2023 Apr 21.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Decitabine
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine
• Other Study ID Numbers: IIT2026008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No