Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allo-HSCT
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A 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) |
Drug: decitabine
15 mg/m2 daily intravenously for consecutive 3 days
Other Names:
Biological: umbilical cord blood
MNC ≥ 3*108 cells; HLA compatibility ≥ 5/6
Other Names:
Drug: Granulocyte-colony stimulating factor
Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L
Other Names:
Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist
Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L
Other Names:
Drug: Recombinant human erythropoietin
Recombinant human erythropoietin will be used when hemoglobin ≤ 85 g/L
Other Names:
|
| Active Comparator: Arm B 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. |
Drug: Granulocyte-colony stimulating factor
Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L
Other Names:
Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist
Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L
Other Names:
Drug: Recombinant human erythropoietin
Recombinant human erythropoietin will be used when hemoglobin ≤ 85 g/L
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
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 14 consecutive weeks;
-
Full donor chimerism;
-
Primary disease in remission;
-
No severe graft-versus- host disease 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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
Investigators
- Principal Investigator: Yue Han, The First Affiliated Hospital of Soochow University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SOOCHOW-HY-2022-12-15