CD45RA-depleted DLI for the Treatment of Refractory/Persistent Viral Infections After Haploidentical Transplantation (CD45RADLITx)

Ex Vivo CD45RA-depleted DLI for the Treatment of Refractory/Persistent Viral Infections After Transplantation: a Prospective, Multicenter, Single-arm, Pragmatic Clinical Study

The goal of this clinical trial is to learn whether giving patients special donor immune cells (called "CD45RA Depleted DLI") can help treat viral infections that have not improved with standard antiviral drugs. These infections occur after a stem cell transplant. The study will also look at the safety of this treatment.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancy; Haplo-identical HCT
• Intervention / Treatment: Biological: CD45RA depleted donor lymphocyte infusion (DLI)

Detailed Description

Due to delayed immune reconstitution and long-term use of immunosuppressants after allogeneic hematopoietic stem cell transplantation, patients remain in a state of prolonged immunocompromise and are prone to various infections, which is one of the leading causes of death after transplantation. The overall response rate of various antiviral drugs ranges from 60% to 80%, meaning 20-40% of patients cannot be effectively treated. Moreover, most antiviral agents have significant toxicities that patients often cannot tolerate. Therefore, finding appropriate and effective antiviral therapeutic strategies is urgently needed for transplant recipients.

Previous studies have indicated that adoptive donor lymphocyte infusion (DLI) can help reconstitute immunity; however, the CD45RA-positive naïve T cells contained in DLI are a major cause of graft-versus-host disease (GVHD). By ex vivo selection to deplete naïve T cells from donor lymphocytes while retaining donor memory T cells (Tm), it may be possible to promote immune reconstitution, clear viral infections, improve the cure rate of viral infections, and reduce the incidence of GVHD. This study is planned as a prospective, multicenter, single-arm, pragmatic clinical trial. We intend to use the CliniMACS® cell selection system to selectively deplete CD45RA-positive T cells ex vivo and infuse the selected donor lymphocytes (DLI) to treat viral infections that are refractory to first-line therapy after hematopoietic stem cell transplantation. We will evaluate the efficacy and safety of this treatment for post-transplant viral infections, as well as its impact on immune reconstitution after transplantation.

Study Objectives:

Primary objective: To evaluate the efficacy and safety of CD45RA Depleted DLI for the treatment of refractory/persistent viral infections after transplantation.

Secondary objective: To evaluate the effect of CD45RA Depleted DLI on the reconstitution of virus-specific T cell (VST) immunity after transplantation.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiaoxia Hu, MD, PhD; Phone Number: 008613795437259; Email: hu_xiaoxia@126.com

Study Locations

• China
  • SH
    • Shanghai, SH, China, 200025
      • Recruiting
      • Ruijin Hospital
      • Contact: Xiaoxia Hu, MD, PhD; Phone Number: 008613795437259; Email: hu_xiaoxia@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Participants must meet all of the following criteria:

• Patients who have undergone hematopoietic stem cell transplantation.
• Presence of viremia and/or viral infection-related disease caused by a single virus or multiple viruses among the following: CMV, EBV, ADV, BK, B19, JC, HHV-6B, HSV1, or HSV2.
• Patients who, after ≥2 weeks of first-line therapy, have persistent viral positivity, no relief or worsening of clinical symptoms, or re-infection with the same pathogen after viral clearance.
• Availability of a suitable lymphocyte donor.
• Adequate organ function, meeting the following laboratory criteria:
• Liver function: ALT and AST ≤ 10 × upper limit of normal (ULN), TBIL ≤ 5 × ULN.
• Renal function: BUN and Cr ≤ 1.25 × ULN.
• No cardiac insufficiency on electrocardiogram (ECG) or echocardiogram.
• Pulmonary function: oxygen saturation > 90% on room air.
• Willingness and ability of the patient or their legal guardian to receive treatment, comply with the treatment plan, follow-up schedule, and laboratory examinations, and provision of signed informed consent before any study-specific procedure.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from this study:

• Active grade II-IV acute graft-versus-host disease (aGVHD).
• Prednisone or equivalent corticosteroid dose > 0.5 mg/kg/day.
• Receipt of anti-thymocyte globulin (ATG), alemtuzumab (Campath), or other T-cell immunosuppressive monoclonal antibodies within 28 days before enrollment.
• Less than 28 days after allogeneic transplantation, or receipt of donor lymphocyte infusion (DLI) or virus-specific T cell (VST) therapy within 28 days before enrollment.
• Uncontrolled or relapsed malignancy.
• Presence of other serious acute or chronic physical or psychiatric conditions, or laboratory abnormalities, that may compromise patient safety or compliance, or that may interfere with informed consent, study participation, follow-up, or interpretation of study results.

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
Experimental: Treatment Group; CD45RA Depleted DLI	Biological: CD45RA depleted donor lymphocyte infusion (DLI); CD45RA depleted donor lymphocyte infusion (DLI) admission with escalated dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Overall Response of Viral Infection Based on Quantitative PCR and Clinical Response Criteria	Overall response rate is defined as the percentage of participants who achieve complete response or partial response after CD45RA-depleted DLI. Complete response is defined as negative viral PCR together with disappearance of all virus-related clinical signs and symptoms. Partial response is defined as at least a 50% reduction in viral load from baseline together with at least 1-grade improvement in clinical symptoms. Overall response rate will be calculated as the number of participants with complete response or partial response divided by the total number of evaluable participants.	90 days after the first CD45RA-depleted donor lymphocyte infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virus-specific T-cell Response	Virus-specific T-cell response will be assessed in peripheral blood using the protocol-specified virus-specific T-cell assay. The assessment may include virus-specific T-cell responses against clinically relevant protocol-specified viruses, including CMV, EBV, adenovirus, BK virus, B19, HHV-6, and JC virus, as applicable to each participant's viral infection. The outcome will summarize the change from baseline in virus-specific T-cell response after CD45RA-depleted DLI.	90 days after the first CD45RA-depleted DLI
Grade III-IV Acute Graft-versus-Host Disease	This outcome will measure the percentage of participants who develop new-onset Grade III-IV acute graft-versus-host disease after CD45RA-depleted DLI. Acute GVHD will be assessed and graded according to MAGIC criteria.	90 days after the first CD45RA-depleted DLI
Chronic Graft-versus-Host Disease	This outcome will measure the percentage of participants who develop chronic graft-versus-host disease after CD45RA-depleted DLI. Chronic GVHD will be assessed and graded according to NIH 2014 criteria, including mild, moderate, and severe chronic GVHD.	Up to 1 years after CD45RA-depleted DLI

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Shanghai Liquan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: DLI; CD45RA
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: RJ-BMT-Infection 1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will share outcome data via request after article publication.

Drug and device information, study documents

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