Decitabine for Poor Graft Function Post Allo-HSCT

Official title

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

Overview

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

Detailed 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.

Interventions

• Drug Decitabine
  Decitabine 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3)
• Drug Granulocyte Colony-Stimulating Factor
  5ug/kg/d when absolute neutrophil count ≤ 1.5 × 109/L
• Drug 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.
• Drug Recombinant human erythropoietin
  10000 U/day when hemoglobin ≤ 85 g/L

Primary outcome measures

• The treatment response [Time frame: day +28]
• Survival [Time frame: 1 year]

Secondary outcome measures (3)

• Bone marrow recovery [Time frame: day +28]
• Relapse and GVHD [Time frame: 3-month]
• Event free survival [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• 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;
• Full donor chimerism;
• Primary disease in remission;
• No severe GVHD and relapse;
• ECOG: 0-2;
• Expected survival longer than 1 month

Exclusion criteria

• Allergic to decitabine;
• Active infections;
• Uncontrolled GVHD;
• Severe organ dysfunction;
• Relapse of underlying malignancies;
• Graft failure;
• Received decitabine or participated in other clinical trials within one month before screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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. PMID 27088376
• 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):9 PMID 16818281
• 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. PMID 34492685
• 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 2 PMID 28323004
• 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: f PMID 21483003
• 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. PMID 33679776
• 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. PMID 33876188
• 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. PMID 33921194

Identifiers

NCT: NCT05907499 · SOOCHOW-HY-2023-06-06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗