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

Phase 3

Not yet recruiting

• Conditions: Poor Graft Function
• Interventions: Drug: decitabine; Biological: umbilical cord blood; Drug: Granulocyte-colony stimulating factor; Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist; Drug: Recombinant human erythropoietin

• Registration Number: NCT05669079
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief 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.

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.

Study Timeline

• Status Verified: 2022-12
• Study First Submitted: 2022-12-19
• Study First Submitted QC: 2022-12-29
• Study First Posted: 2022-12-30
• Last Update Submitted: 2023-06-08
• Last Update Posted: 2023-06-09
• Study Start: 2023-08-01
• Primary Completion: 2026-08-01
• Study Completion: 2026-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	decitabine	decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8)
Arm A	umbilical cord blood	decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8)
Arm A	Granulocyte-colony stimulating factor	decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8)
Arm A	Recombinant human thrombopoietin / thrombopoietin receptor agonist	decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8)
Arm B	Granulocyte-colony stimulating factor	Supportive therapy: G-CSF for patients with absolute neutrophil count ≤ 1.5 × 109/L, rhTPO/TPO-R with platelet count ≤ 30 × 109/L, EPO with hemoglobin ≤ 85g/L.
Arm B	Recombinant human thrombopoietin / thrombopoietin receptor agonist	Supportive therapy: G-CSF for patients with absolute neutrophil count ≤ 1.5 × 109/L, rhTPO/TPO-R with platelet count ≤ 30 × 109/L, EPO with hemoglobin ≤ 85g/L.
Arm A	Recombinant human erythropoietin	decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8)
Arm B	Recombinant human erythropoietin	Supportive therapy: G-CSF for patients with absolute neutrophil count ≤ 1.5 × 109/L, rhTPO/TPO-R with platelet count ≤ 30 × 109/L, EPO with hemoglobin ≤ 85g/L.

Primary Outcome Measures

Name	Time	Method
The treatment response	day +28	The rate of hematological improvement and hematological response of 2 arms
Survival	1 year	The rate of overall survival

Secondary Outcome Measures

Name	Time	Method
Bone marrow recovery	day +28	Number of participants with granulopoiesis, erythropoiesis and megakaryopoiesis recovery of bone marrow
relapse and GVHD	3-month	The rate of relapse and GVHD
Event free survival	1-year	The rate of event free survival