Clinical trial NCT05634915: Clinical Study of rATG Individualized Administration in Haploidentical Hematopoietic Stem Cell Transplantation
Official title: Clinical Study of rATG Individualized Administration for Prevention of GVHD and Maintenance of GVL in Haploidentical Hematopoietic Stem Cell Transplantation.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hematopoietic Stem Cell Transplantation
Acute Leukemia
Keywords: Antithymocyte Globulin
Population pharmacokinetic model
Haploidentical Hematopoietic Stem Cell Transplantation
Acute Leukemia
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2022-12-02
Enrollment: 90
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective, open-label, pairing design, single-center study is to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen（10mg/kg）for patients with acute leukemia undergoing a myeloablative conditioning regimen and haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

Detailed description: Allogeneic hematopoietic stem-cell transplantation (HSCT) is a potentially curative treatment option for acute leukemia. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has become the main choice for acute leukemia in China. Major difficulties of the procedure include graft-versus-host disease (GVHD), graft failure, and relapse. As an important role of haplo-HSCT, Rabbit anti-thymocyte globulin (rATG), a polyclonal rabbit-derived antibody that depletes lymphocytes, including T cells, was introduced to prevent GVHD and transplant rejection.

The recommended dose of rATG in haplo-HSCT is 10 mg/kg. However, while the traditional weight-based rATG dosing regimen (10mg/kg) reduces the incidence of GVHD, it increases the risk of delayed immune reconstitution, viral reactivation, and relapse in patients. Our previous retrospective study showed that active ATG exposure (area under the curve, AUC)) post-transplantation is associated with immune reconstitution, GVHD, relapse, survival, and viral reactivation in HSCT of acute leukemia patients. Identifying the optimal dose of ATG to achieve the optimal exposure range of active ATG is a pressing clinical issue.

The pharmacokinetics of ATG varies significantly in both pediatric and adult populations, especially the active ATG levels, and clarifying the relationship between the pharmacokinetics of ATG and the prognosis of patient outcomes can help in precise treatment. By constructing a population pharmacokinetic model of ATG, we can provide an individualized optimal dose of ATG based on factors prior to transplantation. ATG individualized administration may improve the survival and quality of life of patients undergoing haplo-HSCT. A prospective pairing design trial is required to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen (10mg/kg) for patients with acute leukemia undergoing haplo-HSCT.

Eligibility criteria: Inclusion Criteria:

1. All patients were diagnosed with acute leukemia.
2. All patients should have the indication of Haploidentical hematopoietic stem cell transplant and receive the myeloablative conditioning regimen.
3. 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:

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

Primary outcomes:
measure: Cumulative incidences of aGVHD
timeFrame: 100 days after transplantation
measure: CD4+ immune reconstitution
timeFrame: 3 months after transplantation
measure: Leukemia-free survival (LFS)
timeFrame: 1 years after transplantation
Secondary outcomes:
measure: Cumulative incidences of cGVHD
timeFrame: 1 years after transplantation
measure: Cumulative incidences of EBV reactivation
timeFrame: 1 years after transplantation
measure: Cumulative incidence of CMV reactivation
timeFrame: 1 years after transplantation
measure: Neutrophil engraftment
timeFrame: 1 month after transplantation
measure: Platelet engraftment
timeFrame: 1 month after transplantation
measure: Overall survival (OS)
timeFrame: 1 years after transplantation
measure: GVHD-free and relapse-free survival (GRFS)
timeFrame: 1 years after transplantation
measure: Non-relapse mortality (NRM)
timeFrame: 1 years after transplantation
measure: Relapse-related mortality (RRM)
timeFrame: 1 years after transplantation
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Xiaowen Tang, PhD
role: STUDY_CHAIR
References: