Decitabine for Poor Graft Function Post Allo-HSCT

Study Overview
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Brief Summary
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This randomized trial aims at validating the efficacy and safety of low-dose decitabine for PGF post allo-HSCT.

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 in PGF post allo-HSCT patients.

Official Title
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Low Dose Decitabine 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
* Drug: Granulocyte Colony-Stimulating Factor
* Drug: 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; ECOG: 0-2; Expected survival longer than 1 month Exclusion Criteria: Allergic to decitabine; 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: 70 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 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3) | Drug: Decitabine<br>* Decitabine 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3)<br>* Other names: Dec;Drug: Granulocyte Colony-Stimulating Factor<br>* 5ug/kg/d when absolute neutrophil count ≤ 1.5 × 109/L<br>* Other names: G-CSF;Drug: Thrombopoietin Receptor Agonist<br>* Eltrombopag initial dose: 25 mg orally once a day, may increase to up to 75 mg/day, when platelet count ≤ 30 × 109/L; Avatrombopag initial dose: 20 mg orally once a day, may increase to up to 60 mg/day, when platelet count ≤ 30 × 109/L.<br>* Other names: Eltrombopag / Avatrombopag;Drug: Recombinant human erythropoietin<br>* 10000 U/day when hemoglobin ≤ 85 g/L<br>* Other names: EPO;|
| Active Comparator: Arm B<br>The hematologic growth factors (granulocyte-colony stimulating factor, thrombopoietin receptor agonists, recombinant human erythropoietin) | Drug: Granulocyte Colony-Stimulating Factor<br>* 5ug/kg/d when absolute neutrophil count ≤ 1.5 × 109/L<br>* Other names: G-CSF;Drug: Thrombopoietin Receptor Agonist<br>* Eltrombopag initial dose: 25 mg orally once a day, may increase to up to 75 mg/day, when platelet count ≤ 30 × 109/L; Avatrombopag initial dose: 20 mg orally once a day, may increase to up to 60 mg/day, when platelet count ≤ 30 × 109/L.<br>* Other names: Eltrombopag / Avatrombopag;Drug: Recombinant human erythropoietin<br>* 10000 U/day 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 response of after HSCT | 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 after HSCT | day +28 | 
| Relapse and GVHD | The rate of relapse and GVHD after HSCT | 3-month | 
| Event free survival | The rate of event free survival after HSCT | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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poor graft function, hematopoietic stem cell transplantation