Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allo-HSCT

Official title

Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allogenic Hematopoietic Stem Cell Transplantation

Overview

This randomized trial aimed at validating the efficacy and safety of low-dose decitabine, together with umbilical cord blood in PGF post allo-HSCT patients.

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, together with umbilical cord blood in PGF post allo-HSCT patients.

Patients were eligible if they were 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 14 consecutive weeks, in the presence of full donor chimerism and primary disease in remission without severe graft-versus- host disease (GVHD) and relapse.

Patients with the following conditions or diagnoses were excluded: allergic to decitabine or any components of frozen preservation of umbilical cord blood; active infections; uncontrolled GVHD; severe organ dysfunction; relapse of underlying malignancies; graft failure. Patients were also excluded if they had received decitabine or participated in other clinical trials within one month before screening.

Hematological improvement is defined as recovery of two or three blood lineages: absolute neutrophil count\>1.5 × 109/L, platelet count\>30 × 109/L, hemoglobin\>85g/L, without G-CSF, red blood cell or platelet infusion.

Hematological response is defined as recovery of three blood lineages: absolute neutrophil count\>2.5 × 109/L, platelet count\>60 × 109/L, hemoglobin\>100g/L, without G-CSF, red blood cell or platelet infusion.

No response: failed to achieve hematological improvement or response.

Interventions

• Drug decitabine
  15 mg/m2 daily intravenously for consecutive 3 days
• Biological umbilical cord blood
  MNC ≥ 3\*108 cells; HLA compatibility ≥ 5/6
• Drug Granulocyte-colony stimulating factor
  Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L
• Drug Recombinant human thrombopoietin / thrombopoietin receptor agonist
  Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L
• Drug Recombinant human erythropoietin
  Recombinant human erythropoietin will be used 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.

Exclusion criteria

• Allergic to decitabine or any components of frozen preservation of umbilical cord blood;
• 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
• 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
• 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

Identifiers

NCT: NCT05669079 · SOOCHOW-HY-2022-12-15

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗