ATG Individualized Dosing Model in URD-PBSCT.

NCT06572462 | Recruiting Phase 2

• 1 other identifier: S2023-794-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. A targeted dosing strategy was established based on ATG concentration monitoring and conducted a phase 2 trial to evaluate the safety and efficacy of the dosing strategy in adult unmanipulated haplo-PBSCT, a encouraging result was attained. In this trial, The ATG-targeted dosing strategy was extended to adult unrelated donor allogeneic hematopoietic stem cell transplantation, ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on-3 days and- 2days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days.

Conditions

Cytomegalovirus Infections; Infection Reactivation; Stem Cell Transplant Complications

Outcome Measures

Primary Outcomes (1)

• cumulative incidence of CMV reactivation

  The primary endpoint was the cumulative incidence of CMV reactivation on +180 days after transplantation.

  0Day-180Days

Study Arms (1)

targeted dosing ATG cohort

EXPERIMENTAL

The targeted dosing ATG cohort received the same dose of medication at -5 days and -4 days as the traditional administration method (-5days, 1.5mg/kg; -4days 2.5mg/kg), Two individual doses were given on -3days and day -2days according to the dose adjustment strategy.

Drug: individualized ATG dosing strategy

Interventions

individualized ATG dosing strategy DRUG

Investigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) recipients, who received a conventional fixed dose of 10 mg/kg ATG during conditioning, the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods, was found to be 100-148.5 × 10\^3 UE·d/L. This concentration range was associated with a reduction in CMV/EBV reactivation, without an increase in acute GVHD or malignant disease relapse. Mathematical function was then exploited to determine the total targeted ATG dose on -3days to -2days based on concentrations of active ATG on -5daysto -4days. Based on this function, investigators established a dosing strategy that aimed to maintain the active ATG-AUC within the optimal range.

targeted dosing ATG cohort

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 malignant hematological tumors who have indications for allogeneic hematopoietic stem cell transplantation.
• HLA-matched unrelated donor
• Patient age ≥14 years old and ≤65 years old
• ALT and AST ≤ 2.5 times the upper limit of normal values, bilirubin ≤ 2 times the upper limit of normal values
• Creatinine ≤ high limit of normal value
• No uncontrollable infection or serious mental illness
• Physical strength score is 0-2 (ECOG)
• Sign the informed consent form

You may not qualify if:

• Unrelated donor who is not HLA matched
• No indication for allogeneic hematopoietic stem cell transplantation
• Patient age \<14 years old or \>65 years old
• The donor or recipient are pregnant
• Suffering from mental illness or other conditions and being unable to proceed as planned

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Department of Hematology, First Medical Center of Chinese PLA General Hospital

Beijing, China

RECRUITING

Related Publications (1)

• Chen S, Wang L, Luan S, Wang H, Du J, Ge D, Li F, Wu Y, Gu Z, Dou L, Liu D. Reduced cytomegalovirus reactivation and viremia without increasing GVHD after URD-PBSCT: A prospective study using targeted ATG dosing strategy. Cancer Pathog Ther. 2025 Apr 5;4(2):145-152. doi: 10.1016/j.cpt.2025.04.001. eCollection 2026 Mar.

  PMID: 41624481 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Latent Infection

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• diahong Liu, MD

  First Medical Center of Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheng Chen, master

CONTACT

15101156205; csto301@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 27, 2024
• Study Start: December 31, 2020
• Primary Completion: December 30, 2024
• Study Completion: June 30, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)