Zuberitamab for EBV Infection Post-Allo-HSCT

NCT07261215 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2025118
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

EBV DNAemia is defined as the presence of EBV-DNA load in peripheral blood exceeding the normal threshold, serving as a key diagnostic indicator for EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD). According to the European Conference on Infections in Leukemia (ECIL-6) guidelines, regular monitoring of peripheral blood EBV-DNA levels via quantitative real-time PCR (qPCR) is recommended starting from the first month after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a weekly frequency sustained for at least 4 months post-transplant. For HSCT patients who develop EBV DNAemia, preemptive therapy should be initiated promptly. EBV-PTLD is a serious complication that may progress rapidly; if not diagnosed and treated in a timely manner, mortality rates can reach 60-80%. Current guidelines recommend CD20 monoclonal antibody (rituximab) as the first-line preemptive treatment. The response rate to rituximab is approximately 84%. The typical regimen consists of 375 mg/m² per dose, administered weekly, with 1-4 doses generally sufficient to achieve treatment goals. However, a subset of patients exhibits poor response to first-line therapy and requires second-line interventions, such as EBV-specific cytotoxic T lymphocytes (EBV-CTLs), donor lymphocyte infusion, or combination chemotherapy. Zuberitamab is a novel anti-CD20 monoclonal antibody and the first Class 1 innovative biologics targeting CD20 developed in China. Preclinical studies have demonstrated that zuberitamab exhibits stronger antibody-dependent cellular cytotoxicity (ADCC) activity compared to rituximab. In a pivotal Phase III registrational clinical study, zuberitamab combined with CHOP (Hi-CHOP) was evaluated head-to-head against R-CHOP in patients with diffuse large B-cell lymphoma (DLBCL). The results showed an improvement in the complete response (CR) rate by more than 8% (85.7% vs. 77.3%, P = 0.038). These findings indicate that zuberitamab holds significant advantages over rituximab in terms of both biological activity and clinical efficacy. Based on this evidence, we have initiated a Phase II clinical trial to evaluate the efficacy and safety of zuberitamab as first-line preemptive therapy for EBV infection. This is a prospective Phase II clinical trial enrolling patients with EBV infection following transplantation. Zuberitamab will be administered as first-line preemptive therapy.

Conditions

HSCT; EBV Infection

Outcome Measures

Primary Outcomes (1)

• EBV-DNA clearance rate

  28 days after treatment

Secondary Outcomes (8)

• overall survival (OS)

  180days

• relapse-free survival (RFS)

  180 days

• Treatment-related mortality

  180 days

• Incidence of post-transplant lymphoproliferative disease (PTLD)

  180 days

• Incidence of hemophagocytic syndrome

  180 days

Study Arms (1)

Zuberitamab treatment

EXPERIMENTAL

Drug: Zuberitamab

Interventions

Zuberitamab DRUG

Zuberitamab will be administered as first-line preemptive therapy at a dose of 375 mg/m² on day 1 of each cycle (one cycle = 7 days).

Zuberitamab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Underwent allogeneic hematopoietic stem cell transplantation (HSCT).
• Documented EBV infection, defined as either:
• EBV DNAemia (EBV-DNA ≥400 copies/mL in plasma), or Pathologically confirmed EBV-associated lymphoproliferative disease with positive EBER by in situ hybridization.
• Age ≥18 years, regardless of gender.
• Negative for HIV, HBV, and HCV.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-2.
• Provision of signed informed consent prior to any study-related procedures. For patients aged 18 or above, consent must be provided by the patient themselves or an immediate family member. If obtaining consent directly from the patient is deemed medically detrimental to their condition, consent may be provided by a legal guardian or an immediate family member.

You may not qualify if:

• \. Presence of uncontrolled infection requiring mechanical ventilation or hemodynamic instability at the time of enrollment.
• \. Diagnosis of clinically significant severe hepatic insufficiency (defined as Child-Pugh Class C) within 5 days prior to enrollment.
• \. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding 5 times the upper limit of normal (ULN), or serum total bilirubin exceeding 2 times ULN, within 5 days prior to enrollment.
• \. Diagnosis of end-stage renal dysfunction with a creatinine clearance rate of \<10 mL/min within 5 days prior to enrollment.
• \. Concurrent diagnosis of moderate hepatic insufficiency (defined as Child-Pugh Class B) and moderate renal dysfunction (defined as creatinine clearance rate \<50 mL/min).
• \. Cardiac function or disease meeting any of the following criteria:
• Long QT syndrome or QTc interval \>480 ms.
• Complete left bundle branch block, second-degree or third-degree atrioventricular block.
• Severe, uncontrolled arrhythmia requiring pharmacological intervention.
• New York Heart Association (NYHA) functional classification ≥ Class II.
• Left ventricular ejection fraction (LVEF) \<50%.
• History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other clinically significant arrhythmia requiring treatment within 6 months prior to enrollment; history of clinically significant pericardial disease; or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• \. Presence of uncontrolled severe acute graft-versus-host disease (aGVHD). 8. Evidence of active HIV replication prior to enrollment; detectable HCV antibody and HCV-RNA positivity within 90 days prior to enrollment; or HBsAg positivity. Known seropositivity for HIV or active hepatitis C virus.
• \. Presence of psychiatric disorders or other conditions that would compromise the patient's ability to comply with study treatment and monitoring requirements.
• \. Inability or unwillingness to provide written informed consent. 11. Patients deemed ineligible by the investigator due to other specific circumstances.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

MeSH Terms

Conditions

Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 3, 2025
• Study Start: January 14, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11