AZA Combined With NAC for PIT After HSCT

Study Overview
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Brief Summary
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Prolonged isolated thrombocytopenia (PIT) that is refractory to conventional treatments has remained a critical complication after allogeneic hematopoietic cell transplantation since decades years ago. Recombinant human thrombopoietin (rhTPO) is the main therapy in clinical practice, but remains low efficiency for PIT. Demethylating drugs have shown thier potential in high-risk myelodysplastic syndromes (MDS) and acte myeloid leukemia (AML). In addition, decitabine has demonstrated its efficacy of over 70% for response rate in treatment for PIT in early clinical trials with elusive mechanism. Preliminary experiments revealed that PIT was associated with abnormality of oxidation microenvironment, and N-Acetyl-L-cysteine (NAC) was the most commonly used antioxidant. Therefore, the investigators have been wondering whether Azacitidine in combination with NAC could improve PIT post HSCT and explore the possible mechanism of it.

Detailed Description
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Prolonged isolated thrombocytopenia (PIT) that is refractory to conventional treatments has remained a critical complication after allogeneic hematopoietic cell transplantation since decades years ago. Recombinant human thrombopoietin (rhTPO) is the main therapy in clinical practice, but remains low efficiency for PIT. Demethylating drugs have shown thier potential in high-risk myelodysplastic syndromes (MDS) and acte myeloid leukemia (AML). In addition, decitabine has demonstrated its efficacy of over 70% for response rate in treatment for PIT in early clinical trials with elusive mechanism. Preliminary experiments revealed that PIT was associated with abnormality of oxidation microenvironment, and N-Acetyl-L-cysteine (NAC) was the most commonly used antioxidant. Furthermore, AZA had shown its potential in immune regulation. Therefore, the investigators have been wondering whether Azacitidine in combination with NAC could improve PIT post HSCT and explore the possible mechanism of it.

Official Title
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Azacitidine (AZA) Combined With N-Acetyl-L-cysteine (NAC) for Prolonged Isolated Thrombocytopenia (PIT) After Hematopoietic Stem Cell Transplantation (HSCT)

Conditions
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Thrombocytopenia, Isolated, Stem Cell Transplant Complications

Intervention / Treatment
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* Drug: Azacitidine
* Drug: N Acetyl L Cysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Platelet count ≤ 30 × 10^9/L persistently at day 60 post-HSCT or later; Neutrophil and hemoglobin were well recovered; Full donor chimerism was achieved; Exclusion Criteria: Patients with malignancy relapse; Active infections; Grade Ⅲ-Ⅳ acute graft-versus-host disease or severe chronic graft-versus-host disease according to National Institute of Health criteria; Severe organ damage; Thrombosis requiring treatment;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Arm1: Control Arm2:AZA+NAC
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>receive supportive care | |
| Experimental: AZA+NAC group<br>AZA 50mg Subcutaneous daily d1-d5 + NAC 600mg oral bid d1-28， 28 days for one cycle | Drug: Azacitidine<br>* 28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.<br>* Other names: AZA;Drug: N Acetyl L Cysteine<br>* 28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.<br>* Other names: NAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| platelet reconstruction | platelet count above 50*10^9/L independent of transfusion | From date of randomization until the date of platelet reconstruction, assessed up to 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | the time from the date of day 1 post HSCT to the date of death due to any cause | From date of randomization until the date of death from any cause, assessed up to 1 year | 
| overall response rate | platelet count evaluating above 30*10^9/L but below 50*10^9/L independent of platelet transfusion | From date of randomization until the date of platelet count between 30*10^9/L and 50*10^9/L, assessed up to 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Azacitidine, N-Acetyl-L-cysteine, Prolonged Isolated Thrombocytopenia, Hematopoietic Stem Cell Transplantation