Individualized Application of Anti-Thymocyte Globulin(ATG)in Unrelated Donor Hematopoietic Stem Cell Transplantation

NCT07648992 | Recruiting Phase 4

• 1 other identifier: S2025-1112-01
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to compare individualized anti-thymocyte globulin (ATG) dosing versus conventional fixed-dose regimens in unrelated donor peripheral blood stem cell transplantation (URD-PBSCT). This study notes that URD-HSCT is a key treatment for malignant hematologic diseases and severe bone marrow failure, with rapid expansion in China. However, this study identifies post-transplant CMV infection as a major challenge, adversely affecting survival and quality of life. This study finds that CMV infection compromises immunity and causes multi-organ complications. Given the high costs, long treatment cycles, and limited efficacy of current interventions, this study considers optimizing CMV prevention to be of greater value than expanding treatment options. This study asserts that effective prevention can reduce infection rates and improve overall survival (OS) and long-term prognosis. This study recognizes that ATG is widely used in URD-HSCT to prevent graft-versus-host disease (GVHD), but its dosage is significantly linked to CMV risk. This study indicates that inadequate ATG exposure increases GVHD risk, while excessive exposure raises viral reactivation (e.g., CMV, EBV) and may cause relapse. This study thus identifies balancing GVHD prevention and infection control as a key clinical goal. This study cites Remberger et al. (2004), who compared ATG doses (4-10 mg/kg) in 162 URD-HSCT patients, finding lower doses increased acute GVHD (aGVHD) and 10 mg/kg raised infection-related mortality, suggesting 6-8 mg/kg as a balanced range. This study also references Bacigalupo et al. (2001), who found no survival differences across doses but noted higher doses reduced severe aGVHD at the cost of increased infection. Therefore, this study concludes that optimal ATG dosing requires balancing GVHD, infection, and relapse. This study acknowledges that ATG pharmacokinetics (PK) are complex, influenced by dose, body weight, and absolute lymphocyte count (ALC). This study points out that even with fixed dosing, internal exposure (active ATG-AUC) varies greatly among individuals, indicating that fixed dosing is suboptimal and individualized strategies are needed. This study notes that Admiraal et al. developed an ALC-based individualized ATG model, improving immune reconstitution, reducing viral infections, and enhancing OS. However, this study observes that this model was designed for non-myeloablative conditioning and is not applicable to myeloablative conditioning (MAC), which is standard in China. To address this, this study states that our team initiated ATG PK studies in 2019. This study explains that under MAC, ALC is nearly eliminated, making traditional models unsuitable. By monitoring active ATG-AUC in 106 haploidentical HSCT (haplo-HSCT) patients and using machine learning, this study identified an optimal exposure window of 100-148.5 UE·day/mL. This study found that patients within this window had lower CMV/EBV reactivation without increased GVHD. This study developed a protocol adjusting doses on days -3 and -2 based on ATG concentrations measured on days -5 and -4. This study confirmed through a prospective single-arm study in haplo-HSCT that this regimen reduces CMV/EBV infection and improves disease-free survival (DFS) and OS while maintaining GVHD control. Given the consistency between URD-PBSCT and haplo-PBSCT in conditioning, GVHD prophylaxis, and CMV prevention-and that CMV infection rates in Chinese URD-PBSCT patients reach 65%-70%-this study extends the individualized ATG protocol to URD-PBSCT to validate its universality across donor sources. In summary, building on prior haploidentical transplant research, this study applies individualized ATG dosing to URD-PBSCT. This study aims to precisely regulate ATG exposure to reduce CMV infection while maintaining GVHD prophylaxis. This study seeks to improve patient survival and outcomes, laying the foundation for a population PK model and advancing HSCT toward precision medicine.

Conditions

Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• 1-year GVHD-free and relapse-free survival rate(1-year-GRFS)

  The 1-year GVHD-free and relapse-free survival rate (1-year GRFS) is the proportion of patients who, within one year post-treatment, have not experienced: grade III-IV acute graft-versus-host disease (GVHD), moderate-to-severe chronic GVHD requiring systemic immunosuppression, or disease relapse or progression.

  1 years after treatment

Secondary Outcomes (8)

• overall survival (OS)

  1 years after treatment

• +180 days CMV virus reactivation rate

  180 days post-transplant

• Acute GVHD incidence

  100 days post-transplant

• disease free survival (DFS)

  1 years after treatment

• Cumulative incidence of relapse (CIR)

  1 years after treatment

Study Arms (2)

Experimental group

EXPERIMENTAL

Drug: Anti-Thymocyte Globulin

Control group

ACTIVE COMPARATOR

Drug: Anti-Thymocyte Globulin

Interventions

Anti-Thymocyte Globulin DRUG

Patients receiving individualized dosing of ATG + standard GVHD prophylaxis regimen

Experimental group

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with indications for allogeneic hematopoietic stem cell transplantation, with malignant hematologic diseases in CR1 or CR2 before transplantation.
• Have an HLA-matched sibling, unrelated, or haploidentical donor.
• Age ≥ 14 years and ≤ 65 years.
• Liver function: ALT and AST ≤ 2.5 × upper limit of normal, bilirubin ≤ 2 × upper limit of normal.
• Renal function: creatinine ≤ upper limit of normal.
• No uncontrolled infection or severe mental or psychological disorders.
• ECOG performance status score of 0-2.
• Signed informed consent.

You may not qualify if:

• \- 1.No HLA-matched donor. 2.Malignant hematologic disease in CR3 or higher disease stage, or refractory/relapsed status.
• Patient age \< 14 years or \> 65 years. 4.Pregnancy of either the donor or the recipient. 5.Presence of mental illness or other conditions that preclude compliance with the protocol.

Sponsors & Collaborators

• Daihong Liu: lead
• Peking University People's Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Interventions

Antilymphocyte Serum

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Dai-Hong Liu, Dr.

  Chinese PLA General Hospital

  STUDY CHAIR

Central Study Contacts

Dai-Hong Liu, Dr.

CONTACT

86-010-66937232; daihongrm@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: director

Study Record Dates

• First Submitted: May 9, 2026
• First Posted: June 15, 2026
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: June 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)