AZA Combined With NAC for PIT After HSCT

NCT05126004 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SOOCHOW-HY-2021-2
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Thrombocytopenia, Isolated; Stem Cell Transplant Complications

Keywords

Azacitidine; N-Acetyl-L-cysteine; Prolonged Isolated Thrombocytopenia; Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• overall survival

  From date of randomization until the date of death from any cause, assessed up to 1 year

• overall response rate

  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 (2)

• infection

  From date of randomization until the date of diagnose of infection, assessed up to 100 days

• Severe adverse events

  From date of randomization until the date of occurrence of any severe adverse event, assessed up to 100 days

Study Arms (2)

Control group

NO INTERVENTION

receive supportive care

AZA+NAC group

EXPERIMENTAL

AZA 50mg Subcutaneous daily d1-d5 + NAC 600mg oral bid d1-28， 28 days for one cycle

Drug: Azacitidine; Drug: N Acetyl L Cysteine

Interventions

Azacitidine DRUG

28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.

Also known as: AZA

AZA+NAC group

N Acetyl L Cysteine DRUG

28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.

Also known as: NAC

AZA+NAC group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The first affiliated hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location

Related Publications (11)

• 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.

  PMID: 3881142 BACKGROUND

• 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. doi: 10.1053/bbmt.2001.v7.pm11302549.

  PMID: 11302549 BACKGROUND

• 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.

  PMID: 28642072 BACKGROUND

• 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.

  PMID: 28484721 BACKGROUND

• Ramirez 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.

  PMID: 20921943 BACKGROUND

• 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.

  PMID: 33646303 BACKGROUND

• Mohyeldin A, Garzon-Muvdi T, Quinones-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.

  PMID: 20682444 BACKGROUND

• 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(7):e722. doi: 10.1038/cddis.2013.253.

  PMID: 23846224 BACKGROUND

• 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.

  PMID: 29396859 BACKGROUND

• 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. No abstract available.

  PMID: 26181032 BACKGROUND

• 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.

  PMID: 25566808 BACKGROUND

MeSH Terms

Conditions

Thrombocytopenia

Interventions

Azacitidine; Acetylcysteine

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Yue Han, PhD,MD

CONTACT

0512-67781856; hanyue@suda.edu.cn

Depei Wu, PhD,MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm1: Control Arm2:AZA+NAC

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: November 18, 2021
• Study Start: December 1, 2021
• Primary Completion: June 30, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: November 18, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)