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

Sponsor

Zhujiang Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03190733

Collaborator

Nanfang Hospital of Southern Medical University (Other), First Affiliated Hospital, Sun Yat-Sen University (Other), Second Affiliated Hospital, Sun Yat-Sen University (Other)

192

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft-versus-host-disease Leukemia Relapse	Drug: ATG	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

192 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

A Randomized,Open,Multicenter and Prospective Study of the Optimized Dose of Anti-Thymoglobuline in Haploidentical Allogeneic Stem Cell Transplantation

Anticipated Study Start Date :

Aug 30, 2017

Anticipated Primary Completion Date :

Sep 30, 2020

Anticipated Study Completion Date :

Sep 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ATG 10.0mg/kg ATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg.	Drug: ATG ATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention. Other Names: fludarabine
Active Comparator: ATG 12.5mg/kg ATG 12.5mg/kg group refers to treatment with ATG in the total dose of 12.5mg/kg.	Drug: ATG ATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention. Other Names: fludarabine

Arm

Intervention/Treatment

Experimental: ATG 10.0mg/kg

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

Drug: ATG

ATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention.

Other Names:

fludarabine

Active Comparator: ATG 12.5mg/kg

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

Drug: ATG

Other Names:

fludarabine

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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