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

Chronic Graft-versus-host-disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03190733
• Other study ID #: 2016-XYNK-001
• Status: Not yet recruiting
• Phase: Phase 4
• First received: June 15, 2017
• Last updated: June 15, 2017
• Start date: August 30, 2017
• Est. completion date: September 30, 2021

Study information

• Verified date: December 2016
• Source: Zhujiang Hospital
• Contact: Jianghui xu, Dr
• Phone: 00862062782318
• Email: xiaoxu_75[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 192
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Graft-versus-host-disease
• Graft vs Host Disease
• Leukemia
• Leukemia Relapse
• Recurrence

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Zhujiang Hospital	First Affiliated Hospital, Sun Yat-Sen University, Nanfang Hospital of Southern Medical University, Second Affiliated Hospital, Sun Yat-Sen University

References & Publications (3)

Chang YJ, Wang Y, Mo XD, Zhang XH, Xu LP, Yan CH, Chen H, Chen YH, Chen Y, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long-term outcomes of a prospective randomized trial. Cancer. 2017 Mar 16. doi: 10.1002/cncr.30540. [Epub ahead of print] — View Citation

Lin X, Lu ZG, Song CY, Huang YX, Guo KY, Deng L, Tu SF, He YZ, Xu JH, Long H, Wu BY. Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies. Bone Marrow Transplant. 2015 Aug;50(8):1092-7. doi: 10.1038/bmt.2015.108. Epub 2015 May 11. — View Citation

Long H, Lu ZG, Song CY, Huang YX, Xu JH, Xu JX, Deng L, Tu SF, He YZ, Lin X, Guo KY, Wu BY. Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies. Bone Marrow Transplant. 2016 Nov;51(11):1470-1475. doi: 10.1038/bmt.2016.170. Epub 2016 Jun 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	occurrence of chronic GVHD	chronic GVHD diagnosis based on National Institutes of Health (NIH) criterion	from the day of stem cell transplantation to one year after stem cell transplantation
Secondary	one year cumulative incidence of leukemia relapse	leukemia relapse base on morphology criterion	from the day of stem cell transplantation to one year after stem cell transplantation
Secondary	The cumulative incidence rate of acute GVHD	acute GVHD diagnosis based on NIH criterion	from the day of stem cell transplantation to one year after stem cell transplantation
Secondary	no relapse mortality one year	no relapse death	from the day of stem cell transplantation to one year after stem cell transplantation