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| Name | Class |
|---|---|
| Peking University People's Hospital | OTHER |
| Nanfang Hospital, Southern Medical University | OTHER |
| Ruijin Hospital | OTHER |
| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Group 1 | Experimental | Decitabine in combination with rhTPO. |
|
| Experimental Group 2 | Experimental | Decitabine |
|
| Control Group | Active Comparator | Conventional treatment except decitabine. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine | Drug | Decitabine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Platelet Count Recovery | Platelet response refers to a sustained increase (stable or increasing level) of at least 30×10E9/L independent of transfusion for 3 days. | Up to 4 weeks after the treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Megakaryocyte Count | The total number of megakaryocytes as well as the platelet-shedding megakaryocytes of bone marrow smears (per cm2) was counted and cross-checked by blinded observers. | Up to 4 weeks after the treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Depei Wu, PhD,MD | The First Affiliated Hospital of Soochow University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First affiliated Hospital of SooChow University | Suzhou | Jiangsu | 215000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3881142 | Result | 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. | |
| 21713321 | Result | 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. |
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Two participants from different institutions submitted the applications at the same time when there was only one quota left. Both of them met the inclusion criteria and were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental Group 1 | Decitabine in combination with rhTPO. Decitabine: Decitabine rhTPO: rhTPO |
| FG001 | Experimental Group 2 | Decitabine Decitabine: Decitabine |
| FG002 | Control Group | Conventional treatment except decitabine. Conventional Treatment: immunoglobulin, glucocorticoid etc |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental Group 1 | Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with rhTPO 15000 U daily subcutaneously beginning on day 4 and continuing until the response was achieved or the time of initial evaluation. |
| BG001 | Experimental Group 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Platelet Count Recovery | Platelet response refers to a sustained increase (stable or increasing level) of at least 30×10E9/L independent of transfusion for 3 days. | Posted | Count of Participants | Participants | Up to 4 weeks after the treatment |
|
Study period (4 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental Group 1 | Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with rhTPO 15000 U daily subcutaneously beginning on day 4 and continuing until the response was achieved or the time of initial evaluation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bleeding events | Blood and lymphatic system disorders | Systematic Assessment | Bleeding events (grade ≥3) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypohepatia | Hepatobiliary disorders | Systematic Assessment |
Small number of patients, the diversity of patients, and the heterogeneous treatment options in Arm C.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yaqiong Tang | Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University | +86 18896588075 | tangyaqiong@suda.edu.cn |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Aug 7, 2017 | Apr 9, 2020 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D013921 | Thrombocytopenia |
| D006402 | Hematologic Diseases |
| ID | Term |
|---|---|
| D001791 | Blood Platelet Disorders |
| D006425 | Hemic and Lymphatic Diseases |
| D000095542 | Cytopenia |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D013926 | Thrombopoietin |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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| OTHER |
| Qilu Hospital of Shandong University | OTHER |
| Children's Hospital of Soochow University | OTHER |
| Fujian Medical University Union Hospital | OTHER |
| Hebei Yanda Ludaopei Hospital | OTHER |
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| rhTPO | Drug | rhTPO |
|
|
| Conventional Treatment | Other | immunoglobulin, glucocorticoid etc |
|
| 25566808 | Result | 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. |
| 33646303 | Derived | 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. |
Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3) alone. |
| BG002 | Control Group | Conventional therapies with recommended options including rhTPO, eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, alone or in combination. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Diagnosis | Count of Participants | Participants |
|
| Transplant Donor | Count of Participants | Participants |
|
| ABO compatitibilty | Count of Participants | Participants |
|
| Conditioning | Count of Participants | Participants |
|
| Mononuclear cell infused | Median | Inter-Quartile Range | 10E8/kg |
|
| Neutrophils recovery | Median | Inter-Quartile Range | days |
|
| Enrollment time | Median | Inter-Quartile Range | days |
|
| Platelet counts at enrollment | Median | Inter-Quartile Range | 10E9 platelets/L |
|
| Megakaryocyte counts at enrollment | Median | Inter-Quartile Range | cells/cm^2 |
|
Conventional treatment except decitabine.
Conventional Treatment: immunoglobulin, glucocorticoid etc
|
|
| Secondary | Megakaryocyte Count | The total number of megakaryocytes as well as the platelet-shedding megakaryocytes of bone marrow smears (per cm2) was counted and cross-checked by blinded observers. | Posted | Median | Inter-Quartile Range | cells/cm^2 | Up to 4 weeks after the treatment |
|
|
|
| 1 |
| 30 |
| 4 |
| 30 |
| 8 |
| 30 |
| EG001 | Experimental Group 2 | Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3) alone. | 0 | 30 | 1 | 30 | 5 | 30 |
| EG002 | Control Group | Conventional therapies with recommended options including rhTPO, eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, alone or in combination. | 1 | 31 | 3 | 31 | 7 | 31 |
|
| Infections | Infections and infestations | Systematic Assessment | Infections (Grade >=3) |
|
| Shock | Cardiac disorders | Systematic Assessment |
|
| Chest distress | Cardiac disorders | Systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Fever | Infections and infestations | Systematic Assessment |
|
| Blurred vision | Eye disorders | Systematic Assessment |
|
| Hypeluricemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Erythra | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Bleeding events | Blood and lymphatic system disorders | Systematic Assessment |
|
| Infection | Infections and infestations | Systematic Assessment |
|
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| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| Male |
|
| Acute myeloid leukemia |
|
| Chronic myeloid leukemia |
|
| Myelodyplastic syndrome |
|
| Non-Hodgkin lymphoma |
|
| Matched related donor |
|
| Matched unrelated donor |
|
| ABO mismatched |
|
| Others |
|