AZA Combined With NAC for PIT After HSCT

Stem Cell Transplant Complications Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05126004
• Other study ID #: SOOCHOW-HY-2021-2
• Status: Not yet recruiting
• Phase: Phase 2
• 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
• 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;

Related Conditions & MeSH terms

• Stem Cell Transplant Complications
• Thrombocytopenia

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 all — Click 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