A Randomized Controlled Trial of Prophylactic Rituximab to Reduce Clinically Significant EBV DNAemia After Allogeneic Hematopoietic Stem Cell Transplantation

A Prospective, Randomized, Controlled, Open-Label Clinical Trial With Blinded Endpoint Assessment of Prophylactic Rituximab for Reducing Clinically Significant EBV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

This is a single-center, prospective, randomized, open-label clinical trial with blinded endpoint assessment for patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to explore whether low-dose preventive rituximab can lower the risk of clinically significant Epstein-Barr virus (EBV) viremia within 180 days after transplantation.

Patients aged 16-65 years who receive allo-HSCT and carry medium-to-high risks of EBV reactivation will be enrolled. All eligible participants will be randomly split into two groups at day +21 after transplant at a 1:1 ratio.

Intervention group: Standard post-transplant supportive care plus two low doses of rituximab (100mg intravenous infusion on day +21 and day +28).

Control group: Only standard routine post-transplant management without preventive rituximab.

All participants will receive regular scheduled blood tests and outpatient follow-up visits up to 1 year after transplantation. We will monitor EBV viral load, cytomegalovirus (CMV) infection, graft-versus-host disease (GVHD), infection complications, immune function recovery, as well as long-term survival. We will also record all adverse reactions related to rituximab infusion, low immunoglobulin levels and other safety events.

The main study outcome is the cumulative rate of clinically significant EBV viremia within 180 days post transplant. All endpoint judgments will be completed by independent researchers to reduce assessment bias. This trial hopes to confirm the safety and clinical value of low-dose rituximab prevention, and provide reliable clinical evidence for EBV infection prevention after hematopoietic stem cell transplantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Epstein-Barr Virus Reactivation; Clinically Significant EBV DNAemia
• Intervention / Treatment: Drug: Rituximab (Arm A); Other: Standard Post-Transplant Supportive Care

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Donglin Yang; Phone Number: 02223608592; Email: yangdonglin@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China
    • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
    • Contact: Donglin Yang; Phone Number: 02223608592; Email: yangdonglin@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Aged between 16 and 65 years old. Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinically stable condition allowing administration of study intervention at post-transplant Day +21.

EBV-DNA quantitative test completed within 48 hours prior to randomization. Written informed consent signed by the participant or legal authorized representative.

Exclusion Criteria:

- Presence of clinically significant EBV infection or meeting criteria for EBV preemptive therapy before randomization.

Prior rituximab administration during conditioning regimen. Confirmed or highly suspected post-transplant lymphoproliferative disorder (PTLD).

Severe anaphylactic history to rituximab or any excipients of the preparation. Active uncontrolled severe systemic infection. Active hepatitis B virus (HBV) infection without standardized antiviral prophylaxis or treatment.

Pregnant or breastfeeding female subjects. Subjects judged ineligible for participation by the investigator for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prophylactic Rituximab Group	Drug: Rituximab (Arm A); Intervention Description Patients receive uniform standard allo-HSCT post-transplant care plus two low-dose prophylactic rituximab infusions: 100 mg IV on Day +21 and 100 mg IV on Day +28 after transplantation. Premedication is given before each infusion to avoid infusion reactions.; Other: Standard Post-Transplant Supportive Care; Uniform routine allo-HSCT follow-up care including GVHD prophylaxis, letermovir CMV prophylaxis, blood transfusion, regular viral load monitoring.
Other: Standard Care Control Group	Other: Standard Post-Transplant Supportive Care; Uniform routine allo-HSCT follow-up care including GVHD prophylaxis, letermovir CMV prophylaxis, blood transfusion, regular viral load monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative incidence of clinically significant EBV DNAemia within 180 days after allogeneic hematopoietic stem cell transplantation	From the date of allogeneic hematopoietic stem cell transplantation to Day 180 post-transplant

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of any EBV DNAemia from randomization to Day +180 post-transplant	Randomization day to post-transplant Day 180
Cumulative incidence of post-transplant lymphoproliferative disorder (PTLD) within 1 year	Randomization day to post-transplant Day 365
1-year overall survival (OS)	Randomization day to post-transplant Day 365

Collaborators and Investigators

• Sponsor: Yang Donglin

Study record dates

Study Major Dates

• Study Start (Estimated): July 9, 2026
• Primary Completion (Estimated): July 9, 2027
• Study Completion (Estimated): July 9, 2027

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab
• Other Study ID Numbers: IIT2026080-EC-1

Drug and device information, study documents

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