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

Poor Graft Function Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05669079
• Other study ID #: SOOCHOW-HY-2022-12-15
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 1, 2023
• Est. completion date: November 1, 2026

Study information

• Verified date: December 2022
• Source: The First Affiliated Hospital of Soochow University
• Contact: Yaqiong Tang
• Phone: 18896588075
• Email: tangyaqiong[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: November 1, 2026
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 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.

Exclusion Criteria:

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

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
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
• Recombinant human thrombopoietin / thrombopoietin receptor agonist
Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count = 30 × 109/L
• Recombinant human erythropoietin
Recombinant human erythropoietin will be used 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 (5)

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

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.20 — 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 — 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The treatment response	The rate of hematological improvement and hematological response of 2 arms	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	day +28
Secondary	relapse and GVHD	The rate of relapse and GVHD	3-month
Secondary	Event free survival	The rate of event free survival	1-year