Targeted Dose Study of ATG in Haploidentical Hematopoietic Stem Cell Transplantation

NCT ID: NCT05166967

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2025-07-29

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.

Conditions

Haploidentical Hematopoietic Stem Cell Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Individual dose of ATG

Individual dose of ATG: Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on pharmacokinetic index, within a range of 6 mg/kg to 13mg/kg), and the active ATG concentration ranges from 110 to 148.5UE/ml.

Group Type: EXPERIMENTAL

Individual Antithymocyte globulin

Intervention Type: DRUG

Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on pharmacokinetic index, within a range of 6 mg/kg to 13mg/kg). Prophylaxis against graft versus-host disease (GVHD) was performed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and short-term methotrexate.

Fixed dose of ATG

A total amount of 10mg/kg ATG was divided into 4 days (from day -5 to day -2). The specific usage: 1.5mg/kg for day -5, 2.5mg/kg for day -4 and day -3, 3.5 mg/kg for day -2.

Group Type: ACTIVE_COMPARATOR

Antithymocyte globulin

Intervention Type: DRUG

A 10mg/kg total dose of antithymocyte globulin (ATG) was added to conditioning regimens for 4 days (from day -5 to day -2). Prophylaxis against graft versus-host disease (GVHD) was performed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and short-term methotrexate.

Interventions

Individual Antithymocyte globulin

Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on pharmacokinetic index, within a range of 6 mg/kg to 13mg/kg). Prophylaxis against graft versus-host disease (GVHD) was performed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and short-term methotrexate.

Intervention Type: DRUG

Antithymocyte globulin

A 10mg/kg total dose of antithymocyte globulin (ATG) was added to conditioning regimens for 4 days (from day -5 to day -2). Prophylaxis against graft versus-host disease (GVHD) was performed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and short-term methotrexate.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital, Peking University Institute of Hematology

UNKNOWN

Sponsor Role: collaborator

Department of Hematology, The First Affiliated Hospital of Zhengzhou University

UNKNOWN

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Daihong Liu

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daihong Liu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Locations

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

S2020-484-02

Identifier Type: -

Identifier Source: org_study_id