Efficacy and Safety Study of ATG for Prophylaxis of aGVHD in Matched Sibling Donor PBSCT

aGVHD Clinical Trial

Official title:

Prospective Study of Combined ATG Regimen for Prophylaxis of aGVHD in Matched Sibling Donor PBSCT

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02677181
• Other study ID #: 81370666
• Status: Completed
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: April 2022

Study information

• Verified date: May 2022
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy and safety of combined ATG （antithymocyte globulin ） regimen for aGVHD(acute graft-versus-host disease ) prophylaxis in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT).

Description:

Transplantation with G-CSF （Granulocyte colony stimulating factor ）mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with matched sibling donor transplantation. Unmanipulated haploidentical donor PBSCT (haplo-PBSCT) has been applied in patients with hematologic malignancies. In our previous cohort study, haplo-PBSCT was associated with lower incidence of severe acute GVHD and extensive chronic GVHD compared with matched sibling donor PBSCT (MSD-PBSCT). Haplo-PBSCT has the same GVHD prophylaxis regimen with MSD-PBSCT, except ATG. It suggested the potential advantage of ATG in prophylaxis of GVHD and improvement of long-term quality of life of the transplant recipients, which motivate us to observe the efficacy of combined ATG regimen for GVHD prophylaxis in MSD-PBSCT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 2022
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

1. acute myeloid leukemia (AML) in CR1 (complete remission 1) or CR2 (complete remission 2) phase regardless of cytogenetics;

2. CML CP(chronic myelogenous leukemia , chronic phase); NHL (non-Hodgkin's lymphoma )

3. MDS-RAEB(myelodysplastic syndrome -refractory anemia with excess blasts ).

4. All patients should aged 40 to 70 years

5. Have matched sibling donor.

6. Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases .

Exclusion Criteria:

1. Patients aged less than 40 years old ;

2. Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases;

3. AML patients with t (15;17);

Related Conditions & MeSH terms

• aGVHD

Intervention

Drug:
• ATG
rabbit ATG(Sanofi)
• CsA
cyclosporine (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered.
• mycophenolate mofetil
From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30 for MSD-PBSCT.
• Methotrexate
short-term methotrexate

Locations

Country	Name	City	State
China	Liping Dou	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Chinese PLA General Hospital	309th Hospital of Chinese People's Liberation Army, Beijing Naval General Hospital, Space Center Hospital, Peking University

Country where clinical trial is conducted

China, 

References & Publications (7)

Armand P, Kim HT, Zhang MJ, Perez WS, Dal Cin PS, Klumpp TR, Waller EK, Litzow MR, Liesveld JL, Lazarus HM, Artz AS, Gupta V, Savani BN, McCarthy PL, Cahn JY, Schouten HC, Finke J, Ball ED, Aljurf MD, Cutler CS, Rowe JM, Antin JH, Isola LM, Di Bartolomeo P, Camitta BM, Miller AM, Cairo MS, Stockerl-Goldstein K, Sierra J, Savoie ML, Halter J, Stiff PJ, Nabhan C, Jakubowski AA, Bunjes DW, Petersdorf EW, Devine SM, Maziarz RT, Bornhauser M, Lewis VA, Marks DI, Bredeson CN, Soiffer RJ, Weisdorf DJ. Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant. 2012 Feb;18(2):280-8. doi: 10.1016/j.bbmt.2011.07.024. Epub 2011 Jul 31. — View Citation

Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. doi: 10.1016/S1470-2045(09)70225-6. Epub 2009 Aug 18. — View Citation

Hamadani M, Blum W, Phillips G, Elder P, Andritsos L, Hofmeister C, O'Donnell L, Klisovic R, Penza S, Garzon R, Krugh D, Lin T, Bechtel T, Benson DM, Byrd JC, Marcucci G, Devine SM. Improved nonrelapse mortality and infection rate with lower dose of antithymocyte globulin in patients undergoing reduced-intensity conditioning allogeneic transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2009 Nov;15(11):1422-30. doi: 10.1016/j.bbmt.2009.07.006. Epub 2009 Sep 1. — View Citation

Rezvani AR, Storb RF. Prevention of graft-vs.-host disease. Expert Opin Pharmacother. 2012 Aug;13(12):1737-50. doi: 10.1517/14656566.2012.703652. Epub 2012 Jul 7. Review. — View Citation

Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986 Mar 20;314(12):729-35. — View Citation

Storek J, Mohty M, Boelens JJ. Rabbit anti-T cell globulin in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015 Jun;21(6):959-70. doi: 10.1016/j.bbmt.2014.11.676. Epub 2014 Dec 5. 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	Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)	Chronic graft versus host disease grading criteria (refer to NIH criteria)	three years
Secondary	all cause mortality		two years
Secondary	Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria		two years
Secondary	DFS(disease-free survival )	disease-free survival	two years
Secondary	TRM(treatment-related mortality )	treatment-related mortality	two years
Secondary	Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)		three months