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

NCT02677181 | Completed Phase 4 DMC

• 1 other identifier: 81370666
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

aGVHD

Keywords

ATG; Matched sibling donor; peripheral blood stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• all cause mortality

  two years

• Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria

  two years

• DFS(disease-free survival )

  two years

• TRM(treatment-related mortality )

  two years

• Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)

  three months

Study Arms (2)

ATG combined regimen

EXPERIMENTAL

ATG combined regimen for prophylaxis of GVHD, includes ATG, MMF(Mycophenolate mofetil ),CsA (cyclosporin A) and MTX (methotrexate). All recipients in this arm received ATG, CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. ATG (Thymoglobuline, rabbit) was used as 1.5 mg/kg/d on day -5 and 3.5 mg/kg/d on day -4. CsA (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. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.

Drug: ATG; Drug: CsA; Drug: mycophenolate mofetil; Drug: Methotrexate

no-ATG

ACTIVE COMPARATOR

regimen for prophylaxis of GVHD without ATG. The regimen includes MMF,CsA and MTX.CsA (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. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11.

Drug: CsA; Drug: mycophenolate mofetil; Drug: Methotrexate

Interventions

ATG DRUG

rabbit ATG（Sanofi）

Also known as: Thymoglobuline

ATG combined regimen

CsA DRUG

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.

Also known as: Neoral/Sandimmun

ATG combined regimen; no-ATG

mycophenolate mofetil DRUG

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.

Also known as: MMF（Novartis）

ATG combined regimen; no-ATG

Methotrexate DRUG

short-term methotrexate

Also known as: MTX(Pfizer)

ATG combined regimen; no-ATG

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• acute myeloid leukemia (AML) in CR1 (complete remission 1) or CR2 (complete remission 2) phase regardless of cytogenetics;
• CML CP(chronic myelogenous leukemia , chronic phase); NHL (non-Hodgkin's lymphoma )
• MDS-RAEB(myelodysplastic syndrome -refractory anemia with excess blasts ).
• All patients should aged 40 to 70 years
• Have matched sibling donor.
• Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases .

You may not qualify if:

• Patients aged less than 40 years old ;
• Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases;
• AML patients with t (15;17);

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• 309th Hospital of Chinese People's Liberation Army: collaborator
• Beijing Naval General Hospital: collaborator
• Space Center Hospital, Peking University: collaborator

Study Sites (1)

Liping Dou

Beijing, Beijing Municipality, 100853, China

Location

Related Publications (9)

• 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.

  PMID: 21810400 BACKGROUND

• 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.

  PMID: 22770714 BACKGROUND

• 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. doi: 10.1056/NEJM198603203141201.

  PMID: 3513012 BACKGROUND

• 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, Bornhauser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socie 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.

  PMID: 19695955 BACKGROUND

• 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.

  PMID: 24292519 BACKGROUND

• 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.

  PMID: 19822302 BACKGROUND

• 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.

  PMID: 25482864 BACKGROUND

• Chakupurakal G, Freudenberger P, Skoetz N, Ahr H, Theurich S. Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host disease after allogeneic stem cell or bone marrow transplantation in adults. Cochrane Database Syst Rev. 2023 Jun 21;6(6):CD009159. doi: 10.1002/14651858.CD009159.pub3.

  PMID: 37341189 DERIVED

• Dou L, Wang L, Li X, Liu Y, Li F, Wang L, Gao X, Huang W, Wang S, Gao C, Yu L, Liu D. Role of antithymocyte globulin in matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies. Medicine (Baltimore). 2021 Feb 26;100(8):e24725. doi: 10.1097/MD.0000000000024725.

  PMID: 33663084 DERIVED

MeSH Terms

Interventions

Antilymphocyte Serum; Cyclosporins; Mycophenolic Acid; Methotrexate

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Daihong Liu, Doctor

  Chinese PLA General Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hematology departemnt in Chinese PLA General Hospital

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: February 9, 2016
• Study Start: January 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: April 1, 2022
• Last Updated: May 24, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)