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NCT Number: NCT05166967

Targeted Dose Study of ATG in Haploidentical Hematopoietic Stem Cell Transplantation

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).

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Key information

Conditions

Haploidentical Hematopoietic Stem Cell Transplantation

Age range

14 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Individual Antithymocyte globulin

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.

Antithymocyte globulin

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.

Primary outcomes

  1. GVHD-free and relapse-free survival (GRFS)

    Time frame: 12 months after transplantation

    GRFS is defined as a composite endpoint of death from any cause, disease relapse, grade III-IV acute GVHD, or moderate to severe chronic GVHD requiring systemic immunosuppression therapy.

Secondary outcomes

  1. Cumulative incidences of CMV reactivation

    Time frame: 6 months after transplantation

    CMV reactivation was defined as DNA load ≥ 1×104 copies /mL or ≥ 1×103 copies/mL in two consecutive tests. The cumulative incidence of CMV reactivation by Day +180 post-transplantation was defined as the proportion of CMV reactivation occurring at any monitoring point during 6 months post-transplant.

  2. Incidence of CMV disease

    Time frame: 6 months after transplantation

    The cumulative incidences of CMV disease in participants after transplantation,

  3. Cumulative incidences of EBV reactivation

    Time frame: 6 months after transplantation

    The cumulative incidences of EBV reactivation in participants after transplantation, tested by EBV realtime PCR.

  4. Cumulative incidences of PTLD(posttransplant lymphoproliferative disorders)

    Time frame: 6 months after transplantation

    The cumulative incidences of PTLD in participants after transplantation

  5. Cumulative incidences of aGVHD

    Time frame: 365 days after transplantation

    The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.

  6. Cumulative incidences of cGVHD

    Time frame: 365 days after transplantation

    Chronic GVHD can be classified as "limited" or "extensive" according to the Seattle criteria, and also be classified as "mild" or "moderate" or "severe" according to the National Institutes of Health (NIH) criteria.

  7. Neutrophil engraftment

    Time frame: 1 month after transplantation

    Neutrophil engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count > 0.5 × 10^9/L.

  8. Platelet engraftment

    Time frame: 1 month after transplantation

    Platelet engraftment is defined as the first of 7 consecutive days with an absolute platelet count > 20 × 10^9/L independent from transfusion

  9. Overall survival (OS)

    Time frame: 365 days after transplantation

    Overall survival (OS) is defined as the time from randomization to death resulting from any cause.

  10. Disease-free survival (DFS)

    Time frame: 365 days after transplantation

    Disease-free survival (DFS) is defined as the time from enrollment to relapse of primary disease or death from any cause, whichever occurred first.

  11. Nonrelapse mortality (NRM)

    Time frame: 365 days after transplantation

    Non-relapse mortality (NRM) is defined as the time from enrollment to death of any causes other than hematologic disease relapse.

  12. Infection rate

    Time frame: 365 days after transplantation

    Infection rate is defined as the proportion of participants who developed all kinds of infection

Sponsors and collaborators

Lead sponsor

Chinese PLA General Hospital

Other

Collaborators

  • Peking University People's Hospital, Peking University Institute of Hematology
  • The First Affiliated Hospital of Zhengzhou University

Registry information

Official study title

Impact of Optimal Doses of Antithymocyte Globulin Conditioning on Graft Versus-host Disease and Virus Reactivation in Haploidentical Hematopoietic Stem Cell Transplantation

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Dec 22, 2021
Registry last updated
Jan 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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