PTCy-ATG vs ATG in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis

Hematopoietic Stem Cell Transplantation Clinical Trial

Official title:

A Comparison of PTCy-ATG and ATG Strategy in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03689465
• Other study ID #: PTCy-ATG-2018
• Status: Recruiting
• Phase: Phase 4
• Start date: October 29, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: September 2019
• Source: Nanfang Hospital of Southern Medical University
• Contact: Ren Lin, M.D.
• Phone: +86-020-62787883
• Email: lansinglinren[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The granulocyte colony-stimulating factor (G-CSF)+antithymocyte globulin (ATG)-based protocols and posttransplantation cyclophosphamide (PTCy) protocols have been widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical related donor transplantation (haplo-HSCT). Nevertheless, severe acute GVHD remains an obstacle for haplo-HSCT. This study is aim to evaluate the efficacy of a modified protocol that includes PTCY and ATG in recipients of haplo-HSCT.

Description:

Haploidentical related donor transplantation is now considered an important alternative to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, the strategies for graft-versus-host disease (GVHD) prophylaxis mainly include ex vivo and in vivo T-cell depletion (TCD) in haploidentical HSCT (haplo-HSCT). In vivo TCD modalities have become mainstream including granulocyte colony-stimulating factor (G-CSF)+antithymocyte globulin (ATG)-based protocols and posttransplantation cyclophosphamide (PTCy) protocols. The ATG strategy has been widely used. Nevertheless, severe acute GVHD remains an obstacle for haplo-HSCT. In addition, infections, especially viral infections, remain an important drawback of this strategy. This study is aim to evaluate the efficacy of a modified protocol that includes PTCY and ATG in recipients of haplo-HSCT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: December 31, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• A patient age of 18-65 years

• Haploidentical hematopoietic stem cell transplant recipient

• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)

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

Related Conditions & MeSH terms

• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation

Intervention

Drug:
• ATG
In PTCy-ATG group, ATG will be intravenously infused via a central venous catheter from day -3 until day -1 at a total dose of 4.5mg/kg. In ATG group, ATG will be intravenously infused via a central venous catheter from day -5 until day -2 at a total dose of 7.5mg/kg.
• CTX
In PTCy-ATG group, CTX will be intravenously infused via a central venous catheter on day +4 at a dose of 50mg/kg/d.
• Mycophenolate Mofetil
In PTCy-ATG group, Mycophenolate Mofetil will be taken orally from day +5 with the dosage of 0.5g twice a day. The dosage will be halved from day +30. In ATG group, Mycophenolate Mofetil will be taken orally from day -9 with the dosage of 0.5g twice a day. The dosage will be halved from day +30.
• Ciclosporin A (CsA)
In PTCy-ATG group, Ciclosporin A (CsA) will be intravenously infused from day +5 at a dose of 2.5mg/kg/d. In ATG group, Ciclosporin A (CsA) will be intravenously infused from day -9 at a dose of 2.5mg/kg/d.
• methotrexate (MTX)
In ATG group, methotrexate (MTX) will be intravenously on days +1, +3 and +6.

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing
China	Xiangya Hospital, Central South University	Changsha	Hunan
China	Chenzhou First People's Hospital	Chenzhou	Hunan
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

Baron F, Mohty M, Blaise D, Socié G, Labopin M, Esteve J, Ciceri F, Giebel S, Gorin NC, Savani BN, Schmid C, Nagler A. Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2017 Feb;102(2):224-234. doi: 10.3324/haematol.2016.148510. Epub 2016 Dec 7. Review. — View Citation

Chang YJ, Huang XJ. Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers. Bone Marrow Transplant. 2014 Jul;49(7):873-9. doi: 10.1038/bmt.2014.19. Epub 2014 Feb 24. Review. — View Citation

Wang Y, Fu HX, Liu DH, Xu LP, Zhang XH, Chang YJ, Chen YH, Wang FR, Sun YQ, Tang FF, Liu KY, Huang XJ. Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial. Bone Marrow Transplant. 2014 Mar;49(3):426-33. doi: 10.1038/bmt.2013.191. Epub 2013 Dec 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CMV DNAemia	CMV DNAemia was defined as positive CMV-DNA in the blood when the copies exceeded 500 copies/ml.	1 year posttransplantation
Secondary	aGVHD	aGVHD (acute GVHD) was defined according to the 1994 Consensus Conference on Acute GVHD Grading and graded from I to IV.	100 days 1 year posttransplantation
Secondary	cGVHD	Chronic GVHD (cGVHD) was graded as limited or extensive.	2 year posttransplantation
Secondary	EBV DNAemia	EBV DNAemia was defined as positive EBV-DNA in the blood when the copies exceeded 500 copies/ml.	1 year posttransplantation
Secondary	Leukemia relapse	primary disease relapse	2 year posttransplantation
Secondary	OS	overall survival	2 year posttransplantation
Secondary	DFS	disease-free survival	2 year posttransplantation