ATG Individualized Dosing Model in URD-PBSCT.
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age14-65
SponsorChinese PLA General Hospital
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
individualized ATG dosing strategy
DrugInvestigators 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.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: targeted dosing ATG cohortExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
cumulative incidence of CMV reactivation
The primary endpoint was the cumulative incidence of CMV reactivation on +180 days after transplantation.
Time frame
0Day-180DaysSponsors and contacts
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Source ClinicalTrials.gov