Clinical trial NCT05126004: AZA Combined With NAC for PIT After HSCT
Official title: Azacitidine (AZA) Combined With N-Acetyl-L-cysteine (NAC) for Prolonged Isolated Thrombocytopenia (PIT) After Hematopoietic Stem Cell Transplantation (HSCT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Thrombocytopenia, Isolated
Stem Cell Transplant Complications
Keywords: Azacitidine
N-Acetyl-L-cysteine
Prolonged Isolated Thrombocytopenia
Hematopoietic Stem Cell Transplantation
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2021-11-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm1: Control Arm2:AZA+NAC
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: platelet reconstruction
timeFrame: From date of randomization until the date of platelet reconstruction, assessed up to 100 days
Secondary outcomes:
measure: overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 1 year
measure: overall response rate
timeFrame: 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
Other outcomes:
measure: infection
timeFrame: From date of randomization until the date of diagnose of infection, assessed up to 100 days
measure: Severe adverse events
timeFrame: From date of randomization until the date of occurrence of any severe adverse event, assessed up to 100 days
Locations:
city: Suzhou
country: China
facility: The first affiliated hospital of Soochow University
state: Jiangsu
Study officials:
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