A Optimal Anti-Thymoglobuline (ATG) Dose Decrease cGVHD But Not Increase Leukemia Relapse for Haplo-HSCT

Phase 4

• Conditions: Chronic Graft-versus-host-disease; Leukemia Relapse
• Interventions: Drug: ATG

• Registration Number: NCT03190733
• Lead Sponsor: Zhujiang Hospital

Brief Summary

In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients with acute leukemia (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in fludarabine, busulfan, cyclophosphamide and antilymphocyte globulin (FBCA) pretreatment protocol of Haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The purpose is to compare the incidences of chronic graft vs host disease (cGVHD) in haplo-HSCT recipients receiving different dose ATG and one year leukemia relapse after transplantation. The main objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with haplo-HSCT.

Detailed Description

Human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation is an effective method for the treatment of hematological malignancies. However, high incidence rate of graft-versus-host disease (GVHD) seriously affects the quality of life of patients.

Using ATG in vivo T cell transplantation regimens reduce the rate of acute GVHD (aGVHD) and cGVHD. However, the optimal dose of ATG is unknown, Huang's reported that a prospective, randomized trial, which compared the long-term outcomes of 2 ATG doses used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were received 10 mg/kg or 6 mg/kg of ATG in conditioning regimen. The 5-year cumulative incidence of cGVHD was found to be higher with ATG 6mg/kg (75.0% vs 56.3% \[P = .007\] and moderate-to-severe cGVHD: 56.3% vs 30.4% \[P\<.0001\]. ATG 10mg/kg in conditioning regimen was found to be associated with a lower risk of cGVHD. But the moderate-to-severe cGVHD was as high as 35%. We established the FBCA pretreatment regimen which added ATG and achieve the goal of reducing GVHD. In this FBCA pretreatment regimen the ATG dose was 12.5mg/kg which higher than that of other protocol. The cumulative incidence of grades II-IV aGVHD and cGVHD was 21.9% and 14.3% with the 12.5mg/kg ATG in the FBCA conditioning regimen which was lower than that of ATG 10mg/kg reported by Huang. However, ATG may lead to immunosuppression and lead to slow recovery of immune function and increased infection rate and may increase leukemia relapse after transplantation. What is the optimal does of ATG in FBCA pretreatment regimen which could reduce cGVHD and not increase leukemia relapse after transplantation? Access to ClinicalTrials and other sites found that there was still no related international studies with the FBCA conditioning regimen. We hypothesize that total ATG dose 12.5mg/kg in FBCA pretreatment regimen will decrease cGVHD and not increase leukemia relapse post transplantation.

In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in the FBCA pretreatment protocol of haploidentical hematopoietic stem cell transplantation. The purpose of this study is to compare the incidences of cGVHD and one year leukemia relapse in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis The first objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with HLA haploid hematopoietic stem cell transplantation.

Study Timeline

• Status Verified: 2016-12
• Study First Submitted: 2017-06-15
• Study First Submitted QC: 2017-06-15
• Last Update Submitted: 2017-06-15
• Study First Posted: 2017-06-19
• Last Update Posted: 2017-06-19
• Study Start: 2017-08-30
• Primary Completion: 2020-09-30
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 192

Inclusion Criteria

1. patients age between 14 yeas old and 60 years old
2. patients with acute myeloid leukemia and acute lymphoblastic leukemia who needed stem cell transplantation without available HLA-identical related or unrelated donors

Exclusion Criteria

1. Patients with severe infections
2. patients with major organ abnormal including renal, liver, lung or heart.
3. Patients with any conditions not suitable for the trial (investigators' decision)
4. patients age below 14 years old and more than 60 years old.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATG 10.0mg/kg	ATG	ATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg.
ATG 12.5mg/kg	ATG	ATG 12.5mg/kg group refers to treatment with ATG in the total dose of 12.5mg/kg.

Primary Outcome Measures

Name	Time	Method
occurrence of chronic GVHD	from the day of stem cell transplantation to one year after stem cell transplantation	chronic GVHD diagnosis based on National Institutes of Health (NIH) criterion

Secondary Outcome Measures

Name	Time	Method
one year cumulative incidence of leukemia relapse	from the day of stem cell transplantation to one year after stem cell transplantation	leukemia relapse base on morphology criterion
The cumulative incidence rate of acute GVHD	from the day of stem cell transplantation to one year after stem cell transplantation	acute GVHD diagnosis based on NIH criterion
no relapse mortality one year	from the day of stem cell transplantation to one year after stem cell transplantation	no relapse death