Decitabine for Poor Graft Function Post Allo-HSCT

NCT05907499 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: SOOCHOW-HY-2023-06-06
• Study Type: interventional
• Target: 76
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Poor Graft Function

Keywords

poor graft function; hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• The treatment response

  The rate of hematological response of after HSCT

  day +28

• Survival

  The rate of overall survival

  1 year

Secondary Outcomes (3)

• Bone marrow recovery

  day +28

• Relapse and GVHD

  3-month

• Event free survival

  1 year

Study Arms (2)

Arm A

EXPERIMENTAL

Decitabine 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3)

Drug: Decitabine; Drug: Granulocyte Colony-Stimulating Factor; Drug: Thrombopoietin Receptor Agonist; Drug: Recombinant human erythropoietin

Arm B

ACTIVE COMPARATOR

The hematologic growth factors (granulocyte-colony stimulating factor, thrombopoietin receptor agonists, recombinant human erythropoietin)

Drug: Granulocyte Colony-Stimulating Factor; Drug: Thrombopoietin Receptor Agonist; Drug: Recombinant human erythropoietin

Interventions

Decitabine DRUG

Decitabine 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3)

Also known as: Dec

Arm A

Granulocyte Colony-Stimulating Factor DRUG

5ug/kg/d when absolute neutrophil count ≤ 1.5 × 109/L

Also known as: G-CSF

Arm A; Arm B

Thrombopoietin Receptor Agonist DRUG

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.

Also known as: Eltrombopag / Avatrombopag

Arm A; Arm B

Recombinant human erythropoietin DRUG

10000 U/day when hemoglobin ≤ 85 g/L

Also known as: EPO

Arm A; Arm B

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Related 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.

  PMID: 27088376 BACKGROUND

• 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.

  PMID: 16818281 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 28323004 BACKGROUND

• 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.

  PMID: 21483003 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 23328088 BACKGROUND

• 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.

  PMID: 33646303 BACKGROUND

• 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.

  PMID: 26181032 BACKGROUND

• 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.

  PMID: 12010787 BACKGROUND

MeSH Terms

Interventions

Decitabine; Granulocyte Colony-Stimulating Factor; eltrombopag; avatrombopag

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Yue Han, Professor

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yaqiong Tang, Doctor

CONTACT

18896588075; tangyaqiong@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: June 18, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share