PTCy-ATG vs ATG in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: PTCy-ATG group PTCy-ATG group refers to treatment with PTCy-ATG protocol as GVHD prophylaxis at a total dose of 4.5mg/kg ATG, a dose of 50mg/kg/d cyclophosphamide (CTX), a dose of 2.5mg/kg/d Ciclosporin A （CsA）, and a dose of 1.0g/d Mycophenolate Mofetil(MMF). |
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.
Drug: 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.
Drug: 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.
Drug: 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.
|
| Active Comparator: ATG group ATG group refers to treatment with ATG protocol as GVHD prophylaxis at a total dose of 7.5mg/kg ATG, a dose of 2.5mg/kg/d Ciclosporin A （CsA）, a dose of 1.0g/d Mycophenolate Mofetil(MMF) and methotrexate (MTX, on days +1, +3 and +6). |
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.
Drug: 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.
Drug: 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.
Drug: methotrexate (MTX)
In ATG group, methotrexate (MTX) will be intravenously on days +1, +3 and +6.
|
Outcome Measures
Primary Outcome Measures
- CMV DNAemia [1 year posttransplantation]
CMV DNAemia was defined as positive CMV-DNA in the blood when the copies exceeded 500 copies/ml.
Secondary Outcome Measures
- aGVHD [100 days 1 year posttransplantation]
aGVHD (acute GVHD) was defined according to the 1994 Consensus Conference on Acute GVHD Grading and graded from I to IV.
- cGVHD [2 year posttransplantation]
Chronic GVHD (cGVHD) was graded as limited or extensive.
- EBV DNAemia [1 year posttransplantation]
EBV DNAemia was defined as positive EBV-DNA in the blood when the copies exceeded 500 copies/ml.
- Leukemia relapse [2 year posttransplantation]
primary disease relapse
- OS [2 year posttransplantation]
overall survival
- DFS [2 year posttransplantation]
disease-free survival
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hematology,Nanfang Hospital, Southern Medical University | Guangzhou | Guangdong | China | 510515 |
| 2 | Guangzhou First People's Hospital | Guangzhou | Guangdong | China | |
| 3 | Sun Yat-sen Memorial Hospital, Sun Yat-sen University | Guangzhou | Guangdong | China | |
| 4 | The Third Affiliated Hospital, Sun Yat-Sen University | Guangzhou | Guangdong | China | |
| 5 | Xiangya Hospital, Central South University | Changsha | Hunan | China | |
| 6 | Chenzhou First People's Hospital | Chenzhou | Hunan | China | |
| 7 | Peking University People's Hospital | Beijing | China |
Sponsors and Collaborators
- Nanfang Hospital of Southern Medical University
Investigators
- Principal Investigator: Qifa Liu, Nanfang Hospital of Southern Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- PTCy-ATG-2018