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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05126004
Other study ID # SOOCHOW-HY-2021-2
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date December 1, 2021
Est. completion date June 30, 2026

Study information

Verified date April 2021
Source The First Affiliated Hospital of Soochow University
Contact Yue Han, PhD,MD
Phone 0512-67781856
Email hanyue@suda.edu.cn
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 100
Est. completion date June 30, 2026
Est. primary completion date June 30, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 65 Years
Eligibility 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 ?-? 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;

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Azacitidine
28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.
N Acetyl L Cysteine
28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.

Locations

Country Name City State
China The first affiliated hospital of Soochow University Suzhou Jiangsu

Sponsors (1)

Lead Sponsor Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

References & Publications (11)

Bruno B, Gooley T, Sullivan KM, Davis C, Bensinger WI, Storb R, Nash RA. Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(3):154-62. — View Citation

Chen S, Su Y, Wang J. ROS-mediated platelet generation: a microenvironment-dependent manner for megakaryocyte proliferation, differentiation, and maturation. Cell Death Dis. 2013 Jul 11;4:e722. doi: 10.1038/cddis.2013.253. Review. — View Citation

First LR, Smith BR, Lipton J, Nathan DG, Parkman R, Rappeport JM. Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes. Blood. 1985 Feb;65(2):368-74. — View Citation

Han Y, Tang Y, Chen J, Liang J, Ye C, Ruan C, Wu D. Low-Dose Decitabine for Patients With Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Therapeutic Study. JAMA Oncol. 2015 May;1(2):249-51. doi: 10.1001/jamaoncol.2014.316. — View Citation

Kong Y, Shi MM, Zhang YY, Cao XN, Wang Y, Zhang XH, Xu LP, Huang XJ. N-acetyl-L-cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2018 Jul;93(7):931-942. doi: 10.1002/ajh.25056. Epub 2018 Feb 24. — View Citation

Mohyeldin A, Garzón-Muvdi T, Quiñones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell. 2010 Aug 6;7(2):150-61. doi: 10.1016/j.stem.2010.07.007. Review. — View Citation

Ramírez P, Brunstein CG, Miller B, Defor T, Weisdorf D. Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival. Bone Marrow Transplant. 2011 Jul;46(7):981-6. doi: 10.1038/bmt.2010.218. Epub 2010 Oct 4. — View Citation

Tang Y, Chen J, Liu Q, Chu T, Pan T, Liang J, He XF, Chen F, Yang T, Ma X, Wu X, Hu S, Cao X, Hu X, Hu J, Liu Y, Qi J, Shen Y, Ruan C, Han Y, Wu D. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021 Mar 9;5(5):1250-1258. doi: 10.1182/bloodadvances.2020002790. — View Citation

Wang H, Huang M, Zhao Y, Qi JQ, Chen C, Tang YQ, Qiu HY, Fu CC, Tang XW, Wu DP, Ruan CG, Han Y. Recombinant Human Thrombopoietin Promotes Platelet Engraftment and Improves Prognosis of Patients with Myelodysplastic Syndromes and Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2017 Oct;23(10):1678-1684. doi: 10.1016/j.bbmt.2017.06.010. Epub 2017 Jun 19. — View Citation

Zhao X, Zhao X, Huo M, Fan Q, Pei X, Wang Y, Zhang X, Xu L, Huang X, Liu K, Chang Y. Donor-Specific Anti-Human Leukocyte Antigen Antibodies Predict Prolonged Isolated Thrombocytopenia and Inferior Outcomes of Haploidentical Hematopoietic Stem Cell Transplantation. J Immunol Res. 2017;2017:1043836. doi: 10.1155/2017/1043836. Epub 2017 Apr 16. — View Citation

Zhou H, Hou Y, Liu X, Qiu J, Feng Q, Wang Y, Zhang X, Min Y, Shao L, Liu X, Li G, Li L, Yang L, Xu S, Ni H, Peng J, Hou M. Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia. Thromb Haemost. 2015 May;113(5):1021-34. doi: 10.1160/TH14-04-0342. Epub 2015 Jan 8. — View Citation

* Note: There are 11 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other infection clinical diagnose of infection or evidence of next generation of sequencing(NGS)of body fluid or CT or culture of samples collected from patients From date of randomization until the date of diagnose of infection, assessed up to 100 days
Other Severe adverse events any events that prevent the clinical trial continue besides hepatic injury renal function impairment, et al. From date of randomization until the date of occurrence of any severe adverse event, assessed up to 100 days
Primary 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 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
Secondary 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
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