Individualized Dose Study of ATG in Haploidentical Hematopoietic Stem Cell Transplantation

Chinese PLA General Hospital (301 Hospital)

Status and phase: Active, not recruiting; Phase 2

Conditions: Haploidentical Hematopoietic Stem Cell Transplantation

Treatments: Drug: Antithymocyte Globulin

Study type: Interventional

Funder types: Other

Identifiers

NCT04778618

S2020-484-01

Details and patient eligibility

About

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).

Full description

Acute graft-versus-host disease (aGvHD) is an important complication of haplo-HSCT. 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 postengraftment immunosuppressive regimens.

The regimens for prophylaxis of GVHD based on 10mg/kg rabbit anti-human thymocyte immunoglobin (ATG, Thymoglobulin®, Genzyme Polyclonals S.A.S) effectively reduced the occurrence of grade II-IV aGvHD. However, 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. The investigators found that virus reactivation and acute GVHD were highly affected by ATG exposure (area under the curve, AUC) in previous cohort study. The investigators have found an optimal range of active ATG exposure balancing the efficacy of GVHD prophylaxis and the risk of virus reactivation. The incidence of CMV reactivation and III-IV aGVHD reduced to 60%, 6% respectively.

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.

Enrollment: 63 estimated patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Confirmed diagnosis of hematological malignancies refer to the 2016 WHO classification.
2. Aged 14 to 60 years.
3. Karnofsky or Lansky performance status [27] ≥ 70%. Please refer to Appendix A.
4. First transplantation.
5. Adequate organ function
6. Patient and/or legal guardian must sign informed consent for HSCT.

Exclusion criteria

1. Ex-vivo T-cell depleted grafts.
2. Pregnancy or breast-feeding or unwilling to use proper contraception.
3. Unable to assess whether the malignancy is in complete remission.
4. History of hypersensitivity to any biological product.
5. Sensibility to rabbit proteins or previous treatment with Thymoglobuline®.
6. Subjects with uncontrollable systemic infection (viral, bacterial or fungal).
7. Participation in other trial in which the dose of Thymoglobuline® is fixed other than individualized dose.
8. Unable to sign the informed consent form.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 1 patient group

Individual dose of Thymoglobulin

Experimental group

Description:

Individual dose of Thymoglobulin (r-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 10mg/kg)

Treatment:

Drug: Antithymocyte Globulin