Clinical trial NCT05166967: Individualized Dose Study of ATG in Haploidentical Hematopoietic Stem Cell Transplantation
Official title: Impact of Optimal Doses of Antithymocyte Globulin Conditioning on Graft Versus-host Disease and Virus Reactivation in Haploidentical Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Haploidentical Hematopoietic Stem Cell Transplantation
Keywords: ATG
Haplo-HSCT
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital, Peking University Institute of Hematology
name: Department of Hematology, The First Affiliated Hospital of Zhengzhou University
First posted: 2021-12-22
Enrollment: 204
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random Group Assignment
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the response and toxicity rate of two different dosages (Individualized dosage VS. fixed dosage) of ATG as a prophylaxis for acute GVHD in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT).

Detailed description: Acute graft-versus-host disease (aGvHD) is an important complication of haploHSCT. The Seattle group initially introduced the use of ATG as a treatment for acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation (haplo-PBSCT) recipients. Presently, in both myeloablative and reduced-intensity conditioning (RIC) haplo-PBSCT, ATG is part of post engraftment immunosuppressive regimens. The regimens for prophylaxis of GVHD based on 10mg/kg rabbit anti-human thymocyte immunoglobin (ATG, Thymoglobin®, Genzyme Polyclonals S.A.S) effectively reduced the occurrence of grade II-IV aGvHD. Howevre, the incidence of cytomegalovirus (CMV) and EB virus (EBV) reactivation were higher due to a slower immune reconstitution. The 100-day cumulative incidence of CMV and EBV viremia were both over 70% in our unmanipulated haplo-PBSCT program. The optimal dose of ATG balancing the efficacy of GVHD prophylaxis and the risk of virus reactivation in haplo-PBSCT remains unknown.

Reports on the pharmacokinetics of Thymoglobulin in allo-HSCT revealed a high variability. Recent pharmacokinetic studies have shown that the half-life of total ATG after transplant is longer than the active ATG (which is available to bind to human lymphocytes and causes the desired immunological effects). And active ATG appears more associated with pharmacodynamics effects. In our previous cohort study, we found that virus reactivation and acute GVHD were highly affected by ATG exposure (area under the curve, AUC). We have found an optimal range of active ATG range is 110-148.5UE/ml.day the efficacy of GVHD prophylaxis and the risk of virus reactivation. The cumulative incidence of CMV reactivation and persistent CMV hyperemia at 180 days after transplantation in the optimal total AUC group was 60.57% and 31.52% respectively. Significantly lower than 77.08% and 56.25% in the non-optimal total AUC group.

The results suggested that Individualized dosing of ATG has a potential advantage in balancing the efficacy of GVHD prophylaxis and the risk of virus reactivation in haplo-PBSCT. This may improve the survival and quality of life of patients undergoing haplo-PBSCT. A prospective randomized trial is required to compare the efficacy of Individualized dosage of ATG as a prophylaxis for acute GVHD in haplo-PBSCT.

Eligibility criteria: Inclusion Criteria:

* 1. All patients should have the indication of Haploidentical hematopoietic stem cell transplant.
* 2. All patients should sign an informed consent document indicating that they understand the purpose of and procedures required for the study and be willing to participate in the study.

Exclusion Criteria:

1.Patients with any conditions not suitable for the trial (investigators' decision).

Primary outcomes:
measure: Cumulative incidences of CMV reactivation
timeFrame: 6 months after transplantation
Secondary outcomes:
measure: Incidence of CMV disease
timeFrame: 6 months after transplantation
measure: Cumulative incidences of aGVHD
timeFrame: 365 days after transplantation
measure: Cumulative incidences of cGVHD
timeFrame: 365 days after transplantation
measure: Neutrophil engraftment
timeFrame: 1 month after transplantation
measure: Platelet engraftment
timeFrame: 1 month after transplantation
measure: Overall survival (OS)
timeFrame: 365 days after transplantation
measure: Disease-free survival (DFS)
timeFrame: 365 days after transplantation
measure: GRFS (GVHD free, relapse free survival)
timeFrame: 365 days after transplantation
measure: Nonrelapse mortality (NRM)
timeFrame: 365 days after transplantation
measure: Infection rate
timeFrame: 365 days after transplantation
measure: Cumulative incidences of EBV reactivation
timeFrame: 6 months after transplantation
measure: Cumulative incidences of PTLD(posttransplant lymphoproliferative disorders)
timeFrame: 6 months after transplantation
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Daihong Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
References: