Decitabine for Poor Graft Function Post Allo-HSCT

Poor Graft Function Clinical Trial

Official title:

Low Dose Decitabine for Poor Graft Function Post Allogenic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05907499
• Other study ID #: SOOCHOW-HY-2023-06-06
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2023
• Est. completion date: November 1, 2026

Study information

• Verified date: June 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Yaqiong Tang, Doctor
• Phone: 18896588075
• Email: tangyaqiong[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized trial aims at validating the efficacy and safety of low-dose decitabine for PGF post allo-HSCT.

Description:

Poor graft function (PGF), defined by the presence of multilineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (allo-HSCT). Emerging evidence demonstrates that the inadequate stem cells infusion, bone marrow microenvironment and immune dysregulation play a crucial role in maintaining and regulating hematopoiesis. Current therapies remain debatable, including selected CD34+ cells infusion, mesenchymal stromal cells infusion, prophylactic N-acetyl cysteine administration, etc. Thereafter, the investigators conduct a randomized trial aiming at validating the efficacy and safety of low-dose decitabine in PGF post allo-HSCT patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 76
• Est. completion date: November 1, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Diagnosed as PGF at day 28 post-HSCT or later. PGF was defined as two or three cytopenias, absolute neutrophil count = 1.5 × 109/L, platelet count = 30 × 109/L, hemoglobin = 85g/L, lasting for more than 2 consecutive weeks;

2. Full donor chimerism;

3. Primary disease in remission;

4. No severe GVHD and relapse;

5. ECOG: 0-2;

6. Expected survival longer than 1 month

Exclusion Criteria:

1. Allergic to decitabine;

2. Active infections;

3. Uncontrolled GVHD;

4. Severe organ dysfunction;

5. Relapse of underlying malignancies;

6. Graft failure;

7. Received decitabine or participated in other clinical trials within one month before screening.

Related Conditions & MeSH terms

• Poor Graft Function

Intervention

Drug:
• Decitabine
Decitabine 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3)
• Granulocyte Colony-Stimulating Factor
5ug/kg/d when absolute neutrophil count = 1.5 × 109/L
• Thrombopoietin Receptor Agonist
Eltrombopag initial dose: 25 mg orally once a day, may increase to up to 75 mg/day, when platelet count = 30 × 109/L; Avatrombopag initial dose: 20 mg orally once a day, may increase to up to 60 mg/day, when platelet count = 30 × 109/L.
• Recombinant human erythropoietin
10000 U/day when hemoglobin = 85 g/L

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

References & Publications (12)

Alchalby H, Yunus DR, Zabelina T, Ayuk F, Kroger N. Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transplant. 2016 Sep;51(9):1223-7. doi: 10.1038/bmt.2016.98. Epub 2016 Apr 18. — View Citation

DeSimone J, Koshy M, Dorn L, Lavelle D, Bressler L, Molokie R, Talischy N. Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia. Blood. 2002 Jun 1;99(11):3905-8. doi: 10.1182/blood.v99.11.3905. — View Citation

Ghobadi A, Fiala MA, Ramsingh G, Gao F, Abboud CN, Stockerl-Goldstein K, Uy GL, Grossman BJ, Westervelt P, DiPersio JF. Fresh or Cryopreserved CD34+-Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2017 Jul;23(7):1072-1077. doi: 10.1016/j.bbmt.2017.03.019. Epub 2017 Mar 18. — View Citation

Han P, Hou Y, Zhao Y, Liu Y, Yu T, Sun Y, Wang H, Xu P, Li G, Sun T, Hu X, Liu X, Li L, Peng J, Zhou H, Hou M. Low-dose decitabine modulates T-cell homeostasis and restores immune tolerance in immune thrombocytopenia. Blood. 2021 Aug 26;138(8):674-688. doi: 10.1182/blood.2020008477. — View Citation

Han P, Yu T, Hou Y, Zhao Y, Liu Y, Sun Y, Wang H, Xu P, Li G, Sun T, Hu X, Liu X, Li L, Peng J, Zhou H, Hou M. Low-Dose Decitabine Inhibits Cytotoxic T Lymphocytes-Mediated Platelet Destruction via Modulating PD-1 Methylation in Immune Thrombocytopenia. Front Immunol. 2021 Feb 17;12:630693. doi: 10.3389/fimmu.2021.630693. eCollection 2021. — View Citation

Han Y, Tang Y, Chen J, Liang J, Ye C, Ruan C, Wu D. Low-Dose Decitabine for Patients With Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Therapeutic Study. JAMA Oncol. 2015 May;1(2):249-51. doi: 10.1001/jamaoncol.2014.316. No abstract available. — View Citation

Kopp LM, Ray A, Denman CJ, Senyukov VS, Somanchi SS, Zhu S, Lee DA. Decitabine has a biphasic effect on natural killer cell viability, phenotype, and function under proliferative conditions. Mol Immunol. 2013 Jul;54(3-4):296-301. doi: 10.1016/j.molimm.2012.12.012. Epub 2013 Jan 16. — View Citation

Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, Bacigalupo A. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006 Jul;91(7):935-40. — View Citation

Lubbert M, Suciu S, Baila L, Ruter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Beeldens F, Muus P, Pfluger KH, Coens C, Hagemeijer A, Eckart Schaefer H, Ganser A, Aul C, de Witte T, Wijermans PW. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011 May 20;29(15):1987-96. doi: 10.1200/JCO.2010.30.9245. Epub 2011 Apr 11. — View Citation

Prabahran A, Koldej R, Chee L, Ritchie D. Clinical features, pathophysiology, and therapy of poor graft function post-allogeneic stem cell transplantation. Blood Adv. 2022 Mar 22;6(6):1947-1959. doi: 10.1182/bloodadvances.2021004537. — View Citation

Tang Y, Chen J, Liu Q, Chu T, Pan T, Liang J, He XF, Chen F, Yang T, Ma X, Wu X, Hu S, Cao X, Hu X, Hu J, Liu Y, Qi J, Shen Y, Ruan C, Han Y, Wu D. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021 Mar 9;5(5):1250-1258. doi: 10.1182/bloodadvances.2020002790. — View Citation

Zambuzi FA, Cardoso-Silva PM, Castro RC, Fontanari C, Emery FDS, Frantz FG. Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation. Cells. 2021 Apr 12;10(4):868. doi: 10.3390/cells10040868. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The treatment response	The rate of hematological response of after HSCT	day +28
Primary	Survival	The rate of overall survival	1 year
Secondary	Bone marrow recovery	Number of participants with granulopoiesis, erythropoiesis and megakaryopoiesis recovery of bone marrow after HSCT	day +28
Secondary	Relapse and GVHD	The rate of relapse and GVHD after HSCT	3-month
Secondary	Event free survival	The rate of event free survival after HSCT	1 year