CD45RA-depleted DLI for the Prevention of Viral Infections in High-risk Patients After Haploidentical Transplantation (CD45RADLIPx)

Shanghai Jiao Tong University

Status and phase

Not yet enrolling

Phase 1

Conditions

Hematologic Malignancy

Haplo-identical HCT

Treatments

Biological: CD45RA-depleted DLI

Study type

Interventional

Funder types

Other

Identifiers

NCT07672964

RJ-BMT-Prophylaxis 1.0

Details and patient eligibility

About

The goal of this clinical trial is to learn whether giving patients a special type of donor immune cells (called CD45RA Depleted DLI) can help prevent viral infections after a stem cell transplant. It will also learn about the safety of this treatment. The main questions it aims to answer are:

Does this treatment lower the chance of getting serious viral infections after transplant? What medical problems do patients have when receiving this treatment?

Full description

Following allogeneic hematopoietic stem cell transplantation (allo-HSCT), delayed immune reconstitution and long-term use of immunosuppressants leave patients in a prolonged immunocompromised state, predisposing them to various infections, which represent a leading cause of transplant-related mortality. Conventional antiviral agents such as ganciclovir and valganciclovir are associated with hematologic toxicities, including neutropenia and anemia, potentially complicating post-transplant management. Meanwhile, newer antivirals such as cidofovir have not yet been approved in China, limiting patient access. Antiviral cell therapies, represented by virus-specific T cells (VSTs), are expensive and require prolonged culture periods. Therefore, there is an urgent need to identify effective strategies to prevent viral infections after HSCT, especially in high-risk patients.

Previous studies suggest that adoptive donor lymphocyte infusion (DLI) can facilitate immune reconstitution; however, the CD45RA-positive naïve T cells contained in conventional DLI are a major cause of graft-versus-host disease (GvHD). By depleting naïve T cells from donor lymphocytes ex vivo while retaining donor memory T cells (Tm), it is possible to promote post-transplant immune reconstitution without increasing the risk of GvHD. This study plans to conduct a prospective, multicenter, single-arm pragmatic clinical trial. Using the CliniMACS® cell selection system, we will selectively deplete CD45RA-positive T cells ex vivo and infuse the CD45RA-depleted donor lymphocytes (i.e., CD45RA Depleted DLI) to prevent viral infections in high-risk patients after transplantation. The efficacy, safety, and impact on post-transplant immune reconstitution of this regimen will be evaluated.

Primary objective: To evaluate the efficacy and safety of CD45RA Depleted DLI in preventing viral infections in high-risk patients after transplantation.

Secondary objective: To evaluate the impact of CD45RA Depleted DLI on immune reconstitution after transplantation.

Enrollment

30 estimated patients

Sex

All

Ages

14 to 50 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Participants must meet all of the following criteria:

Patients undergoing allogeneic hematopoietic stem cell transplantation (any conditioning regimen or graft source is allowed).
Presence of at least one high-risk factor for post-transplant viral infection (any of the following):
Age ≥50 years or ≤14 years
Non-sibling matched transplantation
In vivo or ex vivo T-cell depletion
Myeloablative conditioning
Conditioning containing radiotherapy
Second transplantation
CMV IgG or EBV IgG donor/recipient mismatch (donor positive, recipient negative)
History of grade II or higher acute graft-versus-host disease (aGVHD) after transplantation and use of high-dose corticosteroids (prednisone equivalent ≥1 mg/kg/day)
Availability of a suitable lymphocyte donor (see "Donor Selection Criteria").
Adequate organ function meeting the following laboratory criteria:
Liver function: ALT and AST ≤10× upper limit of normal (ULN); total bilirubin ≤5× ULN
Renal function: BUN and creatinine ≤1.25× ULN
No cardiac dysfunction on electrocardiogram or echocardiogram
Pulmonary function: oxygen saturation >90% without supplemental oxygen
The patient or legal guardian has the desire and request to receive treatment, signs the informed consent form before treatment, and is willing to comply with the treatment plan, follow-up schedule, and laboratory tests.

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)
Active aGVHD requiring prednisone or equivalent corticosteroid >0.5 mg/kg/day
Active viral infection
Uncontrolled or relapsed malignancy
Other serious acute or chronic physical or psychiatric conditions, or laboratory abnormalities, that may compromise patient safety or compliance, or affect informed consent, study participation, follow-up, or interpretation of results.