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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Poor Graft Function

Intervention / Treatment
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* Drug: decitabine
* Biological: umbilical cord blood
* Drug: Granulocyte-colony stimulating factor
* Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist
* Drug: Recombinant human erythropoietin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>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<br>* 15 mg/m2 daily intravenously for consecutive 3 days<br>* Other names: Dec;Biological: umbilical cord blood<br>* MNC ≥ 3*108 cells; HLA compatibility ≥ 5/6<br>* Other names: UCB;Drug: Granulocyte-colony stimulating factor<br>* Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L<br>* Other names: G-CSF;Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist<br>* Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L<br>* Other names: rhTPO/TPO-RA;Drug: Recombinant human erythropoietin<br>* Recombinant human erythropoietin will be used when hemoglobin ≤ 85 g/L<br>* Other names: EPO;|
| Active Comparator: Arm B<br>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<br>* Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L<br>* Other names: G-CSF;Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist<br>* Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L<br>* Other names: rhTPO/TPO-RA;Drug: Recombinant human erythropoietin<br>* Recombinant human erythropoietin will be used when hemoglobin ≤ 85 g/L<br>* Other names: EPO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The treatment response | The rate of hematological improvement and hematological response of 2 arms | day +28 | 
| Survival | The rate of overall survival | 1 year | 

Secondary Outcome Measures

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