Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06572462
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-23
Brief Title:
ATG Individualized Dosing Model in URD-PBSCT
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Application of Thymoglobulin ATG Individualized Dosing Model in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Detailed Description:
Allogeneic hematopoietic cell transplantationallo-HCT is a curative therapy for hematological disorders and the ATG is commonly used as prophylaxis for GVHD Previous studies have indicated that there is an optimal dosage for ATG administration if the dosage is too high it may affect engraftment and increase the risk of infection and relapse whereas an inadequate dosage may increase the risk of acute or chronic GVHD there is still controversy about the optimal dose of ATG its pharmacologic effects on clinical outcomes of HSCT are associated with donor source human leukocyte antigen HLA disparity conditioning intensity and GVHD prophylaxis so although has been investigated for decades the optimal dosage of ATG in allogeneic hematopoietic stem cell transplantation remains undetermined
ATG exerts pharmacologic effects in its active form upon binding to lymphocytes and its exposure is presented as the area under the concentration-time curve AUC To obtain plasma active ATG concentrations investigators developed an active ATG concentration detection method based on flow-cytometry with HUT-78 T-cells In previous study investigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation haplo-PBSCT recipients who received a conventional fixed dose of 10 mgkg ATG during conditioning the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods was found to be 100-1485 103 UEdL This concentration range was associated with a reduction in CMVEBV 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 a dosing strategy was established that aimed to maintain the active ATG-AUC within the optimal range To validate this individualized dosing strategy investigators conducted a single-arm phase 2 trial demonstrating that this strategy could reduce CMVEBV reactivation and improve survival without increasing the incidence of GVHD after haplo-PBSCT Given the similarity between unrelated donor hematopoietic stem cell transplantation URD-HSCT and haploidentical hematopoietic stem cell transplantation haplo-HSCT in terms of conditioning regimens GVHD prophylaxis and supportive therapies as well as the conventional fixed dose of 10mgkg employed in both settings investigators have designed and conducted a single-center prospective single-arm clinical trial The aim of this trial is to translate the individualized ATG dosing strategy which was originally developed based on ATG concentration monitoring in haplo-HSCT patients to URD-HSCT with the goal of further validating its effectiveness
ATG exerts pharmacologic effects in its active form upon binding to lymphocytes and its exposure is presented as the area under the concentration-time curve AUC To obtain plasma active ATG concentrations investigators developed an active ATG concentration detection method based on flow-cytometry with HUT-78 T-cells In previous study investigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation haplo-PBSCT recipients who received a conventional fixed dose of 10 mgkg ATG during conditioning the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods was found to be 100-1485 103 UEdL This concentration range was associated with a reduction in CMVEBV 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 a dosing strategy was established that aimed to maintain the active ATG-AUC within the optimal range To validate this individualized dosing strategy investigators conducted a single-arm phase 2 trial demonstrating that this strategy could reduce CMVEBV reactivation and improve survival without increasing the incidence of GVHD after haplo-PBSCT Given the similarity between unrelated donor hematopoietic stem cell transplantation URD-HSCT and haploidentical hematopoietic stem cell transplantation haplo-HSCT in terms of conditioning regimens GVHD prophylaxis and supportive therapies as well as the conventional fixed dose of 10mgkg employed in both settings investigators have designed and conducted a single-center prospective single-arm clinical trial The aim of this trial is to translate the individualized ATG dosing strategy which was originally developed based on ATG concentration monitoring in haplo-HSCT patients to URD-HSCT with the goal of further validating its effectiveness
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None