RecruitingPhase 2NCT06572462

ATG Individualized Dosing Model in URD-PBSCT.

Application of Thymoglobulin (ATG) Individualized Dosing Model in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.

Sponsor

Chinese PLA General Hospital

Enrollment

30 participants

Start Date

Dec 31, 2020

Study Type

INTERVENTIONAL

Conditions

Stem Cell Transplant Complications Cytomegalovirus Infections Infection Reactivation

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.

Eligibility

Min Age: 14 YearsMax Age: 65 Years

Inclusion Criteria8

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

Exclusion Criteria5

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

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Interventions

DRUGindividualized ATG dosing strategy

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.