Clinical trial NCT02487563: Prospective Study of Patients With Thrombocytopenia Following HSCT
Official title: A Prospective Study of Patients With Isolated Thrombocytopenia Following Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thrombocytopenia
Hematologic Diseases
Keywords: Isolated thrombocytopenia
decitabine
rhTPO
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: Nanfang Hospital, Southern Medical University
name: Ruijin Hospital
name: Wuhan Union Hospital, China
name: Qilu Hospital of Shandong University
name: Children's Hospital of Soochow University
name: Fujian Medical University Union Hospital
name: Hebei Yanda Ludaopei Hospital
First posted: 2015-07-01
Enrollment: 97
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Isolated thrombocytopenia is a common and severe complication of HSCT, which often leads to an increased risk of life-threatening hemorrhage, frequent requirement of platelet transfusions and extended hospital stays, representing a challenging clinical problem. Current treatments for thrombocytopenia after HSCT are frequently unsatisfactory in platelet recovery and for preventing potentially fatal bleeding complications. Therefore, it is urgent to explore an effective therapy to improve the outcomes of thrombocytopenia after HSCT. Previous studies have demonstrated that decitabine, a hypomethylating agent, may reduce platelet transfusions in myelodysplastic syndrome (MDS) patients. The investigators conducted an prospective clinical trial to evaluate the safety and efficiency of rhTPO and decitabine in the treatment of thrombocytopenia following HSCT.

Detailed description: Isolated thrombocytopenia is a frequent and severe complication of hematopoietic stem cell transplantation (HSCT). It often leads to an increased risk of life-threatening hemorrhage, frequent requirement of platelet transfusions and extended hospital stays, representing a challenging clinical problem. Current treatments for thrombocytopenia after HSCT, including thrombopoietin, interleukin-11, immunoglobulin, methylprednisolone and rituximab, are frequently unsatisfactory in platelet recovery. Therefore, it is urgent to explore an effective therapy to improve the outcomes of thrombocytopenia after HSCT. Thrombopoietin (TPO) is a cytokine that drives thrombopoiesis by stimulating the differentiation of stem cells into megakaryocytes and promoting megakaryocyte proliferation and polyploidization. Decitabine was approved for the treatment of myelodysplastic syndrome (MDS) as a DNA methylation inhibitors. Studies in vitro show that decitabine enhances platelet release and megakaryocyte maturation. Here, the investigators performed a prospective clinical trial, in order to investigate the safety and efficiency of rhTPO and decitabine in the treatment of thrombocytopenia following HSCT.

Eligibility criteria: Inclusion Criteria:

1. Platelet count ≤ 30 × 109/L persistently at day 60 post-HSCT or later;
2. Neutrophil and hemoglobin were well recovered;
3. Full donor chimerism was achieved;
4. No response to conventional treatments (e.g. thrombopoietin, immunoglobulin, glucocorticoid alone or in combination) for a duration of at least 4 weeks;

Exclusion Criteria:

1. Patients with malignancy relapse;
2. Active infections;
3. Grade Ⅲ-Ⅳ acute GVHD or severe chronic GVHD according to National Institute of Health criteria;
4. Severe organ damage;
5. Thrombosis requiring treatment;
6. Received decitabine following the current transplantation.

Primary outcomes:
measure: Number of Participants With Platelet Count Recovery
timeFrame: Up to 4 weeks after the treatment
Secondary outcomes:
measure: Megakaryocyte Count
timeFrame: Up to 4 weeks after the treatment
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First affiliated Hospital of SooChow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, PhD,MD
role: STUDY_CHAIR
References:
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.
citation: Wang J, Yi Z, Wang S, Li Z. The effect of decitabine on megakaryocyte maturation and platelet release. Thromb Haemost. 2011 Aug;106(2):337-43. doi: 10.1160/TH10-11-0744. Epub 2011 Jun 28.
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.
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.