Conditions: Thrombocytopenia Hematologic Diseases
Keywords: Isolated thrombocytopenia decitabine rhTPO
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 97
Healthy volunteers: no

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.

Arms:
arm 1: Decitabine in combination with rhTPO. arm 2: Decitabine arm 3: Conventional treatment except decitabine.

Interventions: intervention 1: Decitabine intervention 2: rhTPO intervention 3: Conventional Treatment
Intervention descriptions: intervention 1: Decitabine intervention 2: rhTPO intervention 3: immunoglobulin, glucocorticoid etc

Protocol document:
Prot_SAP_ICF_000.pdf: 
 
 
 
 
 
Study Protocol 
 
 
 
Low-dose decitabine for refractory prolonged isolated 
thrombocytopenia after hematopoietic cell transplantation 
 
Vision 3.0 
 
Aug. 07, 2017 
 
 
 
ClinicalTrials.gov Identifier: NCT02487563 
 
Principal Investigator 
Yue Han, MD, PhD, hanyue@suda.edu.cn; Depei Wu, MD, PhD, 
wudepei@suda.edu.cn. Jiangsu Institute of Hematology, The First Affiliated 
Hospital of Soochow University, Suzhou 215006, China. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
2 
Table of Contents 
Protocol amendments ...................................................................................... 4 
Protocol summary ............................................................................................ 5 
Background ...................................................................................................... 7 
Refractory prolonged isolated thrombocytopenia after allogeneic 
hematopoietic cell transplantation ................................................................ 7 
rhTPO for thrombocytopenia ........................................................................ 8 
Decitabine for thrombocytopenia after HCT ................................................. 8 
Reference ................................................................................................... 10 
Rationale of this study .................................................................................... 12 
Study objectives ............................................................................................. 12 
Primary objective and primary endpoint ..................................................... 12 
Secondary objectives and secondary endpoints: ....................................... 12 
Research design ............................................................................................ 12 
Type of study .............................................................................................. 12 
Experimental diagram ................................................................................. 13 
Subject selection ............................................................................................ 14 
Inclusion criteria .......................................................................................... 14 
Exclusion criteria ......................................................................................... 14 
Treatment allocation ................................................................................... 15 
Procedures for randomization ..................................................................... 15 
Dosage and administration ......................................................................... 15 
Study process ................................................................................................. 16 
Screening phase ......................................................................................... 16 
Treatment period ........................................................................................ 17 
Termination phase ...................................................................................... 17 
Follow-up phase ......................................................................................... 18 
Response evaluation ...................................................................................... 18 
Safety evaluations .......................................................................................... 18 
Safety endpoints ......................................................................................... 19 
Clinical symptoms ....................................................................................... 19 
Laboratory examination .............................................................................. 19 
Adverse event ................................................................................................ 19 
Definition and record of an adverse event .................................................. 19 
Classification of adverse event severity ...................................................... 19 
Relevance ................................................................................................... 20 
Serious adverse event ................................................................................ 20 
Definition of an unexpected adverse event ................................................. 21 
Expected adverse events ........................................................................... 21 
Procedures of all adverse event ................................................................. 21 
Monitoring committee ................................................................................. 22 
Statistical methods ......................................................................................... 22 
Sample size estimation ............................................................................... 23 


Vision 3.0 
 
3 
Statistical analysis ...................................................................................... 23 
Management of product quality complaint ...................................................... 24 
Procedures ................................................................................................. 24 
Study drug information ................................................................................... 24 
Ethical statement ............................................................................................ 25 
Ethical principles ......................................................................................... 25 
Information and informed consent .............................................................. 25 
Withdrawal from the study .......................................................................... 26 
Identity and privacy of patients ................................................................... 26 
Responsibility of independent ethics committee ......................................... 27 
Responsibility of investigator .......................................................................... 28 
Publications .................................................................................................... 29 
Organization and responsibility ...................................................................... 29 
Appendix ........................................................................................................ 30 
Appendix 1. The score of bleeding ............................................................. 31 
Appendix 2. ECOG score ........................................................................... 32 
Appendix 3. Criteria for IBMTR severity index for acute GVHD ................. 33 
Appendix 4. NIH global severity of chronic GVHD ...................................... 34 
Appendix 5. The table of study procedure .................................................. 35 
Appendix 6: Patient consent form for study participation ............................ 36 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
4 
Protocol amendments 
 
Protocol version 
Issue date 
Vision 1.0 
Sep. 01, 2015 
Vision 2.0 
Mar. 21, 2016 
Vision 3.0 
Aug. 07, 2017 
 
Vision 3.0 (Aug. 07, 2017) 
Applicable Section 
Study centers: 
The First Affiliated Hospital of Soochow University, Suzhou 215006, China;  
Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 
Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 
Shanghai 200025, China; 
Peking University People's Hospital, Beijing 100044, China; 
Wuhan Union Hospital, Wuhan 430022, China; 
Qilu Hospital of Shandong University, Jinan 250012, China. 
Description of Changes 
Three other institutions took part in this study: 
Fujian Medical University, Union Hospital, Fuzhou 350001, China; 
Children’s Hospital of Soochow University, Suzhou 215025, China; 
Hebei Yanda Lu Daopei Hospital, Langfang 065201, China. 
 
 
Vision 2.0 (Mar. 21, 2016) 
Applicable Section 
Secondary objectives and secondary endpoints: 
To evaluate the megakaryocyte counts, white blood cell counts, hemoglobin 
level, renal and liver function at week 4. 
Description of Changes 
Secondary objectives and secondary endpoints: 
To evaluate the megakaryocyte counts and survival during a follow-up of 24 
weeks. 
 


Vision 3.0 
 
5 
Protocol Summary 
Study centers 
• The First Affiliated Hospital of Soochow University, Suzhou 215006, 
China;  
• Nanfang Hospital, Southern Medical University, Guangzhou 510515, 
China;  
• Fujian Institute of Hematology, Fuzhou 350001, China;  
• Children’s Hospital of Soochow University, Suzhou 215025, China;  
• Hebei Yanda Lu Daopei Hospital, Langfang 065201, China;  
• Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 
Shanghai 200025, China; 
• Peking University People's Hospital, Beijing 100044, China; 
• Wuhan Union Hospital, Wuhan 430022, China; 
• Qilu Hospital of Shandong University, Jinan 250012, China. 
Principal Investigator 
Yue Han, MD, PhD; Depei Wu, MD, PhD. 
Methodology 
A prospective, open-label, three-arm, multicenter, randomized clinical trial. 
Primary objective 
To assess the efficacy of low-dose decitabine in patients with refractory 
prolonged isolated thrombocytopenia after hematopoietic cell 
transplantation. 
Secondary objectives 
To evaluate the number of megakaryocytes and survival during a follow-up 
of 24 weeks. 
Inclusion criteria 
• Platelet count < 30 × 109/L for more than 60 days post-HCT;  
• Recovered neutrophil and hemoglobin concentrations;  
• Donor chimerism >95% detected by short-tandem repeat-polymerase 
chain reaction;  
• No response to conventional treatments for thrombocytopenia for a 
duration of at least 4 weeks; 
Exclusion criteria 
• Patients with disease relapse;  
• Active infections requiring treatment;  
• Grade Ⅲ-Ⅳ acute GVHD or severe chronic GVHD according to National 
Institute of Health criteria;  
• Severe organ damage (cardiac, renal and/or hepatic dysfunction greater 
than grade 2 according to the Common Terminology Criteria for Adverse 
Events V5.0);  


Vision 3.0 
 
6 
• Thrombosis requiring treatment;  
• Received decitabine following the current transplantation; 
Intervention  
• Arm A: decitabine 15 mg/m2 daily for consecutive 3 days, combined with 
recombinant human thrombopoietin 300 U/kg daily;  
• Arm B: decitabine 15 mg/m2 daily for consecutive 3 days alone;  
• Arm C: conventional therapies; 
Total number of patients: 96 
Total duration of the study: 4 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
7 
Background 
Refractory prolonged isolated thrombocytopenia after allogeneic 
hematopoietic cell transplantation 
Thrombocytopenia is a frequent and worrisome complication after 
hematopoietic cell transplantation (HCT)1-4, described in 5-37% of the 
recipients5-8, which is not only associated with disease relapse or graft 
rejection, but also significantly correlates with increased incidence of 
transplant-related complications and a higher mortality rate1,9. However, it is 
very difficult to decipher the precise etiology of thrombocytopenia during the 
post-transplant period in a clinical setting. Possible pathogenesis includes 
graft-failure, drugs, veno-occlusive disease, cytomegalovirus infection, 
opportunistic infection, recurrence of the primary disease, graft-versus-host 
disease (GVHD), etc4.  
The major causes of thrombocytopenia include accelerated peripheral platelet 
destruction by antiplatelet antibodies and the insufficient production of 
platelets from marrow megakaryocytes (MKs). In previous studies, both 
increased platelet turnover and impaired thrombopoiesis have been reported 
to be involved in the development of thrombocytopenia after HCT6. 
Furthermore, impaired bone marrow (BM) vascular microenvironment also 
contribute to the occurrence of thrombocytopenia after allo-HCT, including 
cellular elements (bone marrow endothelial cells, perivascular cells, etc), and 
MK-active factors (stromal cell-derived factor-1, vascular endothelial growth 
factor, etc)10. 
Previous studies showed thrombocytopenia after HCT was closely associated 
with a poor survival, and any haemorrhagic complications may thus prove to 
be fatal5. Therefore, successful management of thrombocytopenia following 
HCT is essential in order to achieve and maintain a favorable outcome. Some 
patients may respond to conventional practices including recombinant human 


Vision 3.0 
 
8 
thrombopoietin (rhTPO), interleukin-11, immunoglobulin, methylprednisolone. 
However, there is also a proportion of patients without an identified cause who 
are often resistant to these conventional treatments for thrombocytopenia. We 
describe these patients as refractory prolonged isolated thrombocytopenia 
(RPIT). 
rhTPO for thrombocytopenia 
TPO is a hematopoietic growth factor that stimulates the proliferation and 
differentiation 
of 
hematopoietic 
stem 
cells, 
primitive 
progenitors, 
megakaryocytes, and platelets11-13. In vitro and vivo studies, TPO has been 
proven to be the principal physiologic cytokine that stimulates platelet 
production14-15. Both preclinical and clinical studies revealed that rhTPO or TPO 
receptor (TPOR) agonists could promote platelet recovery in thrombocytopenia 
patients16-19. TPOR agonists, such as eltrombopag and romiplostim, have also 
been shown effective in thrombocytopenia patients after HCT19-20, which still 
needs more large-scale, prospective studies to verify.  
Decitabine for thrombocytopenia after HCT 
Decitabine (5-aza-2´-deoxycytidine) is a deoxycytidine analog which acts as a 
hypomethylating agent that is incorporated into DNA and forms irreversible 
covalent adducts with DNA-methyltransferases. Emerging studies showed 
decitabine can increase platelet count and megakaryocyte numbers21-24. 
Decitabine was found to be able to induce mouse megakaryoblastic cell to 
differentiate into a megakaryocyte-like polyploidy cells. Additionally, a 30% 
platelet count increase in mice 12 hours after the injection of decitabine at a 
clinically relevant dose (15 mg/m2) was observed21. In vitro study, dectibine 
can promote megakaryocyte maturation and platelet production and enhance 
TRAIL expression in megakaryocytes of immune thrombocytopenia24. Our 
previous study suggested that low-dose decitabine, could significantly 


Vision 3.0 
 
9 
increase the platelet count by increasing the number of megakaryocytes of 
thrombocytopenia after HCT, but with limited cases22. Herein, a prospective, 
open-label, three-arm, randomized clinical trial will be conducted to validate 
the efficacy and safety of low-dose decitabine in RPIT patients after HCT and 
to preliminarily explore the potential mechanisms of RPIT.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
10
Reference 
1. Kim DH, Sohn SK, Jeon SB, et al. Prognostic significance of platelet 
recovery pattern after allogeneic HLA-identical sibling transplantation and its 
association with severe acute GVHD. Bone Marrow Transplantation 2006; 
37(1): 101-108. 
2. Akpek G, Lee SJ, Flowers ME, et al. Performance of a new clinical grading 
system for chronic graft-versus-host disease: a multicenter study. Blood 2003; 
102(3): 802-809. 
3. First LR, Smith BR, Lipton J, et al. Isolated thrombocytopenia after 
allogeneic bone marrow transplantation: existence of transient and chronic 
thrombocytopenic syndromes. Blood 1985; 65(2): 368-374. 
4. Nash RA, Gooley T, Davis C, et al. The Problem of Thrombocytopenia after 
Hematopoietic Stem Cell Transplantation. Oncologist 1996; 1(6): 371-380. 
5. Ramrez P, Brunstein CG, Miller B, et al. Delayed platelet recovery after 
allogeneic transplantation: a predictor of increased treatment-related mortality 
and poorer survival. Bone Marrow Transplantation 2011; 46(7): 981-986. 
6. Yamazaki R, Kuwana M, Mori T, et al. Prolonged thrombocytopenia after 
allogeneic hematopoietic stem cell transplantation: associations with impaired 
platelet production and increased platelet turnover. Bone Marrow Transplant 
2006; 38(5): 377-384. 
7. Bruno B, Gooley T, Sullivan KM, et al. Secondary failure of platelet 
recovery after hematopoietic stem cell transplantation. Biol Blood Marrow 
Transplant 2001; 7(3): 154-162. 
8. Klumpp TR, Block CC, Caligiuri MA, et al. Immune-mediated cytopenia 
following bone marrow transplantation. Case reports and review of the 
literature. Medicine (Baltimore) 1992; 71(2): 73-83. 
9. Kuzmina Z, Eder S, Bohm A, et al. Significantly worse survival of patients 
with NIH-defined chronic graft-versus-host disease and thrombocytopenia or 
progressive onset type: results of a prospective study. Leukemia 2012; 26(4): 
746-756. 
10. Kong Y, Hu Y, Zhang XH, et al. Association between an impaired bone 
marrow vascular microenvironment and prolonged isolated thrombocytopenia 
after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow 
Transplant 2014; 20(8): 1190-1197. 
11. Kaushansky K. Thrombopoietin: the primary regulator of platelet 
production. Blood 1995; 86(2): 419-431. 
12. Wendling F. Thrombopoietin: its role from early hematopoiesis to platelet 
production. Haematologica 1999; 84(2): 158-166. 


Vision 3.0 
 
11
13. Kaushansky K. Thrombopoietin: understanding and manipulating platelet 
production. Annu Rev Med 1997; 48: 1-11. 
14. Kaushansky K, Lok S, Holly RD, et al. Promotion of megakaryocyte 
progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. 
Nature 1994; 369(6481): 568-571. 
15. Alexander WS, Roberts AW, Nicola NA, et al. Deficiencies in progenitor 
cells of multiple hematopoietic lineages and defective megakaryocytopoiesis 
in mice lacking the thrombopoietic receptor c-Mpl. Blood 1996; 87(6): 2162-
2170. 
16. Thachil J, Salter I and George J N. Complete remission of refractory 
immune thrombocytopenia (ITP) with a short course of Romiplostim. Eur J 
Haematol 2013; 91(4): 376-377. 
17. Neunert CE, Grace RF. Thrombopoietin-receptor agonists in children with 
immune thrombocytopenia. Lancet 2015; 386(10004): 1606-1609. 
18. Wang Y, Wang Z, Wu L, et al. Recombinant human thrombopoietin is an 
effective treatment for thrombocytopenia in hemophagocytic 
lymphohistiocytosis. Ann Hematol 2013; 92(12): 1695-1699 
19. Battipaglia G, Ruggeri A, Brissot E, et al. Safety and feasibility of 
romiplostim treatment for patients with persistent thrombocytopenia after 
allogeneic stem cell transplantation. Bone Marrow Transplant 2015; 50(12): 
1574-1577. 
20. Reid R, Bennett JM, Becker M, et al. Use of eltrombopag, a 
thrombopoietin receptor agonist, in post-transplantation thrombocytopenia. 
Am J Hematol 2012; 87(7): 743-745. 
21. Wang J, Yi Z, Wang S, et al. The effect of decitabine on megakaryocyte 
maturation and platelet release. Thrombosis and Haemostasis 2011; 106(2): 
337-343. 
22. Han Y, Tang Y, Chen J, et al. Low-Dose Decitabine for Patients With 
Thrombocytopenia 
Following 
Allogeneic 
Hematopoietic 
Stem 
Cell 
Transplantation: A Pilot Therapeutic Study. JAMA Oncol 2015; 1(2): 249-251. 
23. van den Bosch J, Lübbert M, Verhoef G, et al. The effects of 5-aza-2-
deoxycytidine (Decitabine) on the platelet count in patients with intermediate 
and high-risk myelodysplastic syndromes. Leukemia Research 2004; 28(8): 
785-790. 
24. Zhou H, Hou Y, Liu X et al. Low-dose decitabine promotes megakaryocyte 
maturation and platelet production in healthy controls and immune 
thrombocytopenia. Thromb Haemost 2015; 113(5): 1021-1034. 
 
 


Vision 3.0 
 
12
Rationale of this study 
Ø RPIT, a frequent complication after HCT, is often resistant to conventional 
treatment and leads to a poor prognosis; 
Ø A proportion of patients without an identified cause are often resistant to 
conventional treatments for thrombocytopenia; 
Ø We previously demonstrated low-dose decitabine, a hypomethylating agent, 
could significantly increase the platelet count by increasing the number of 
megakaryocytes; 
Ø This randomized trial will be conducted to validate the efficacy and safety of 
low-dose decitabine in RPIT patients after HCT and to preliminarily explore 
the potential mechanisms. 
Study objectives 
Primary objective and primary endpoint 
Primary objective: 
This study aims to validate the efficacy of low-dose decitabine in HCT-RPIT 
patients. 
Primary endpoint: 
The primary endpoint is the recovery of platelet count of HCT-RPIT patients. 
Secondary objectives and secondary endpoints: 
To evaluate the megakaryocyte counts and survival during a follow-up of 24 
weeks. 
Research design 
Type of study  
This is a prospective, open-label, randomized, three-arm clinical trial. 


Vision 3.0 
 
13
 
Experimental diagram 
The overall design of the study is shown in Figure 1. 
 
Figure 1. The flow chart of the overall study design 
Notes: HCT, hematopoietic cell transplantation; GVHD, graft-versus-host disease; rhTPO, 
recombinant human thrombopoietin.  
 
 
 
 
 


Vision 3.0 
 
14
Subject selection 
Inclusion criteria 
Ø Platelet count < 30 × 109/L for more than 60 days post-HCT;  
Ø Recovered neutrophil and hemoglobin concentrations;  
Ø Donor chimerism >95% detected by short-tandem repeat-polymerase chain 
reaction;  
Ø No response to conventional treatments for thrombocytopenia (rhTPO, 
immunoglobulin, rituximab and glucocorticoid, either alone or in 
combination) for a duration of at least 4 weeks. 
Exclusion criteria 
Ø Patients with disease relapse;  
Ø Active infections requiring treatment;  
Ø Grade Ⅲ-Ⅳ acute GVHD or severe chronic GVHD according to National 
Institute of Health criteria;  
Ø Severe organ damage (cardiac, renal and/or hepatic dysfunction greater 
than grade 2 according to the Common Terminology Criteria for Adverse 
Events V5.0);  
Ø Thrombosis requiring treatment;  
Ø Received decitabine following the current transplantation. 
Note:  
Ø If a subject’s status changes (including laboratory results) and meets the 
exclusion criteria after screening but before the first dose of the study drug 
is given, he/she should be excluded from this study.  
Ø Patients suffered from disease relapse would be excluded from this study 
during the 4-week study period as the relapse evidence of a small number 
of patients is negative during screening procedure, but it turns to be positive 
in the process of disease progression. 


Vision 3.0 
 
15
Treatment Allocation 
Subjects will be randomized after the investigator has verified that all eligibility 
criteria have been met. Subjects will be randomized in a 1:1:1:1 ratio to 
receive decitabine in combination with rhTPO (Arm A), decitabine alone (Arm 
B) or conventional treatment except decitabine (Arm C). 
Procedures for randomization 
Completely randomized block design method was performed to assign the 
patients into the 3 arms. For each study site, we produced the random series 
and corresponding assigning arm A, B, C, in which the block equals to 5 and 
length equals to 6. If the length <= 2 then the group is A, 3-4 is B, and 5-6 is 
C. 
Dosage and administration 
Treatment: 
Arm A: decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 
to day 3), combined with rhTPO 300 U/kg daily subcutaneously beginning on 
day 4 and continuing until the response was achieved or the time of initial 
evaluation (day 28);  
Arm B: decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 
to day 3) alone;  
Arm C: conventional therapies with recommended options including rhTPO, 
eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, 
alone or in combination. 
Note:  
Ø For patients with neutropenia (neutrophils ≤0.5×109/L), the granulocyte 
colony-stimulating factor (G-CSF, 5 ug/kg·d) should be administrated to 
reduce the chance of neutropenia related infections. Prophylactic platelet 
transfusion is required for no-bleeding patients with platelet counts lower 
than 20×109/L and those with bleeding and platelet counts lower than 


Vision 3.0 
 
16
30×109/L. For those with severe anemia (hemoglobin ≤ 60 g/L), washed red 
blood cells should be given. 
Ø There is no need of special treatment for transient fever (except infections 
related fever), muscle soreness, dizziness. 
Ø Decitabine treatment should be suspended when some non-hematologic 
toxicities appear as follows: 
• Serum creatinine ≥ 2.0mg/dL; 
• Serum aminotransferase or total bilirubin higher than 2 fold the upper-limit 
of normal level. 
Concomitant therapy 
Except the study drug, other therapies (including immunosuppressant, 
antibiotics, proton-pump inhibitor, diuretic, nutritional therapy, etc) must be 
recorded in the eCRF for the main study treatment period. 
The concurrent administration of other drugs which are known as 
myelosuppression is not recommended unless absolutely necessary. 
Study process 
Screening phase (3 days) 
Ø Inclusion /Exclusion Criteria 
Ø Demographic data: age, sex, nationality, address, spouse's characteristics, 
contact information. 
Ø General information: past history, allergic history, previous disease and 
status, transplant type, conditioning regimen, number of infused stem cells, 
the time of neutrophils reconstitution after HCT, the time of enrollment after 
HCT, other complications except thrombocytopenia, other 
myelosuppression therapies. 
Ø Physical examination: height, body weight, blood pressure, body 
temperature, heart rate, body surface area, respiratory and cardiovascular 


Vision 3.0 
 
17
system examination, nervous system examination, Eastern Cooperative 
Oncology Group (ECOG) score, etc. 
Ø Laboratory examination: 
• Blood analysis: blood routine test, blood biochemistry, virological testing, T-
lymphocyte subsets, platelet-associated antibody, serum TPO level* 
• BM examination: marrow morphology examination (megakaryocyte 
including: platelet-shedding megakaryocyte, granular megakaryocyte, 
naked megakaryocyte), endothelial progenitor cell*, etc. 
Note: * represents blood or BM needs to be collected and sent to the group 
leader institution for examination, in which blood 2 mL is anticoagulated using 
sodium citrate and BM 8 mL is anticoagulated by ethylene diamine tetraacetic 
acid (EDTA). Both bone marrow and blood should be transported under 4℃.  
Ø Electrocardiogram test. 
Treatment period (28 days) 
Ø Drugs will be given based on the protocol;  
Ø Blood routine test and blood biochemistry are performed once a day and 
once a week, respectively. 
Ø Important vital signs are recorded; 
Ø Adverse events will be recorded and managed according to this protocol. 
Termination phase 
Ø Demographic data: age, sex, nationality, address, spouse's characteristics, 
contact information. 
Ø General information: past history, allergic history, previous disease and 
status, transplant type, conditioning regimen, number of infused stem cells, 
the time of neutrophils reconstitution after HCT, the time of enrollment after 
HCT, other complications except thrombocytopenia, other 
myelosuppression therapies. 


Vision 3.0 
 
18
Ø Physical examination: height, body weight, blood pressure, body 
temperature, heart rate, body surface area, respiratory and cardiovascular 
system examination, nervous system examination, ECOG score, etc. 
Ø Laboratory examination: 
• Blood analysis: blood routine test, blood biochemistry, virological testing, T-
lymphocyte subsets, platelet-associated antibody, serum TPO level* 
• Bone marrow examination: marrow morphology examination 
(megakaryocyte including: platelet-shedding megakaryocyte, granular 
megakaryocyte, naked megakaryocyte), endothelial progenitor cell*, etc. 
Note: * represents blood or BM needs to be collected and sent to the group 
leader institution for examination, in which blood 2 mL is anticoagulated using 
sodium citrate and BM 8 mL is anticoagulated by ethylene diamine tetraacetic 
acid (EDTA). Both bone marrow and blood should be transported under 4℃.  
Ø Electrocardiogram test. 
Follow-up phase (6 months)  
Ø Routine blood examination will be repeated once every 1 month; 
Ø The changes of other complications; 
Ø Survival will be long-term recorded until death.  
Response evaluation 
Ø Response: A sustained increase (stable or increasing level) of at least 
30×109/L independent of transfusion for 3 days. 
Ø No response: The requirements for “response” can not be met.    
Safety evaluations 
Safety and tolerability are assessed throughout the study.  


Vision 3.0 
 
19
Safety endpoints 
White blood cell count, hemoglobin, liver function, renal function. 
Clinical symptoms: 
Newly occurred symptoms during the study period: fever, nausea, cough, 
somnolence, depression, constipation, diarrhea, petechia, edema, pharyngitis, 
pulmonary edema, atrial fibrillation, tachycardia, mycobacterium avium 
complex infectious, hyperglycemia，neutropenia, anemia. 
Laboratory examination 
Blood routine test, blood biochemistry, virological testing, electrocardiogram, 
etc. 
Adverse event 
Definition and record of an adverse event 
Adverse events are defined as any harmful medical manifestations occurring 
in a person who participates in a biomedical research whether this 
manifestation is related to the research or the product used in the research. 
An adverse effect may be any unfavourable or unexpected sign (including 
abnormal laboratory results), any symptom or temporary disorder associated 
with the use of the product, with or without relation to the product. 
The clinically significant abnormality must be reported as an adverse event 
(AE) in the eCRF, and AE is supposed to record the time of occurrence, the 
stage of severity, the duration of time, measures and outcomes.   
Classification of adverse event severity  
Every case report is performed by the grade of severity about drug adverse 
reactions： 
Ø Mild: usually transient symptoms unaffecting the daily life; 


Vision 3.0 
 
20
Ø Moderate: symptoms probably affecting the daily life; 
Ø Severe: symptoms seriously affecting the daily life. 
Relevance  
Ø Definite relevance: The adverse event is clearly related to the 
investigational agent. For example, an event that follows a reasonable 
temporal sequence from administration of the study intervention abides by 
a known or expected response pattern to the suspected intervention, which 
improves by stoppage and reappears through repeated exposures, but is 
unable to be reasonably explained by the known characteristics of the 
subject’s clinical state; 
Ø Possible relevance: An adverse event that follows a reasonable temporal 
sequence from administration of the study intervention abides by a known 
or expected response pattern to the suspected intervention, which can be 
easily induced by various other factors; 
Ø Irrelevance: The adverse event is clearly uncorrelated with the research 
agent or procedure. For example, there exists another plausible cause, 
and/or a clinically plausible temporal sequence is inconsistent with the 
onset of the event and the study intervention and/or a causal relationship is 
considered biologically implausible. 
Serious adverse event: 
A serious adverse event (SAE) event is defined as the event with one of the 
following consequences:  
Ø Death; 
Ø Life-threatening condition;  
Ø Hospitalization or extension of hospitalization; 
Ø Temporary or permanent disability; 
Ø Congenital anomaly or malformation; 


Vision 3.0 
 
21
Ø Important medical events: although the event caused by the drug which 
may endanger the subjects may not be life-threatening and result in death 
or require hospitalization, medical or surgical intervention requires to be 
taken to prevent one of the outcomes based on the appropriate medical 
judgment.  
Definition of an unexpected adverse event: 
An unexpected adverse event of the product is defined as the event with the 
nature, severity or course non-corresponding to the product information 
mentioned in the summary when it is authorized or in the investigator's 
brochure when it is not authorized. 
Expected adverse events: 
Ø Due to myelosuppression 
 Neutropenia related infections, fever; 
Bleeding: ecchymosis, petechial, haematemesis, hemoptysis, melena, 
hematuresis, etc; 
Weary, somnolence, pale, etc (due to anemia); 
Ø Due to other non-hematological toxicity 
Liver dysfunction; 
Renal dysfunction; 
Ø Related to the haematological disease 
   Death 
Relapse of any kind 
Ø Related to drug allergy 
Erythra, edema, pruritus, swelling, etc. 
Procedures of all adverse event 
Investigators must immediately take necessarily measures at once to protect 
subjects’ safety, when serious adverse events occur. Furthermore, all adverse 


Vision 3.0 
 
22
events should be followed up and investigated, and detailed records are 
supposed to be made and signed. 
All serious and non-serious AEs and special situation will be reported from the 
signature to completion of the subject’s last study-related procedure (which 
may include the follow-up contact for safety). SAEs must be reported using 
the Serious Adverse Event Form. The sponsor will evaluate any safety 
information that is spontaneously reported by an investigator beyond the time 
frame specified in the protocol. 
All AEs, regardless of the severity or presumed relationship with the study 
treatment, must be recorded in the source document and eCRF using medical 
terminology. Whenever possible, diagnosis should be made when signs and 
symptoms are caused by the common etiology. Investigators must record 
their opinions on the relationship between AEs and the study treatment in the 
eCRF. All measures required for (serious) AEs must be recorded in the 
source document and reported according to sponsor instructions. 
Monitoring committee 
A safety committee comprised of 3 persons independent of the trial will be 
organized and will meet to check the safety related to the study treatment 
during the study. In terms of the overall mortality of each arm and serious 
adverse events, review will be performed by the independent safety 
committee. The committee is responsible for 
haemovigilance/pharmacovigilance of the study and acts as an additional 
warning sign against haemovigilance/pharmacovigilance of the study. 
Contact 
Yue Han (Email: hanyue@suda.edu.cn), Depei Wu (wudepei@suda.edu.cn), 
The First Affiliated Hospital of Soochow University, Suzhou 215006, China. 
Statistical methods 


Vision 3.0 
 
23
Statistical analysis will be done by the sponsor or under the authority of the 
sponsor. A general description of the statistical methods to be used to analyze 
the efficacy and safety data is outlined below. Baseline for all analyses will be 
the day of randomization unless otherwise specified. 
Sample size estimation 
We used the formula of sample size estimate when comparing the 
independent rates more two groups. According to the previous study, among 
the 3 groups, we suppose the biggest effective rate was 80% (Pmax), and the 
lowest rate was about 35% (Pmin). Under the condition of α=0.05(2-tailed), 
β=0.20(1-tailed), ν=2, so λ=9.63, the theoretical sample size for each group 
can be calculated as follow, 
 
n =
𝜆
2(arcsin
𝑝,-. −arcsin
𝑝,01)3 =
9.63
2(arcsin
0.80 −arcsin
0.35)3
= 21.42 
 
Taking account of the 20% of loss rate of follow up, so the sample size for 
each group at least was 25, and the total sample size should at least be 75. 
Statistical analysis 
Completely randomized block design method was performed to assign 
the patients into the 3 arms. Numerical data was presented as medians with 
interval quartile range (IQR), and categorical data were shown as proportions. 
One-way ANOVA was used to compare the difference for the means among 3 
treatment arms. Since there was no statistical difference in response or 
survival between Arms A and B, these data were combined for subsequent 
comparisons to Arm C. Chi-square test or Wilcoxon rank test was used to 
compare the difference for the proportions among 3 treatment arms. Kaplan-
Meier method was performed to estimate the 1-year survival rate for the 3 
arms respectively and log-rank test to compare their difference for the survival 


Vision 3.0 
 
24
curves. Cox model and logistic model were used to estimate independent 
association for the HR (hazard ratio), OR (odds ratio) and 95% CI (confidence 
interval) among the treatment arms. A significance level was set as a 2-tailed 
P value of < .05. All the analyses used the SPSS 19.0 (SPSS Inc.).   
Management of product quality complaint 
A product quality complaint (PQC) is defined as any suspicion of a product 
defect related to manufacturing, labeling, or packaging, ie, any dissatisfaction 
relative to the identity, quality, durability, or reliability of a product, including its 
labeling or package integrity. PQCs may have an impact on the safety and 
efficacy of the product. Timely, accurate, and complete reporting and analysis 
of PQC information from clinical studies are crucial for the protection of 
subjects, investigators, and the sponsor, and are mandated by regulatory 
agencies worldwide.  
Procedures 
All initial PQCs must be reported to the sponsor by the investigational staff 
within 24 hours after being made aware of the event. 
If the defect is combined with an SAE, the investigational staff must report the 
PQC to the sponsor according to the SAE reporting timelines. A sample of the 
suspected product should be maintained for further investigation if requested 
by the sponsor. 
Study drug information 
Ø Decitabine is a kind of white sterile lyophilized powder, placed in a clear, 
colorless vial. Each 20 mL vial contains 25 mg decitabine.  
Ø rhTPO is a sterile‚ clear‚ colorless liquid. The single-use vial contains 15 
000 U rhTPO when the fill volume is 1.0 mL. 


Vision 3.0 
 
25
Ethical statement 
Ethical principles 
The study should be carried out in accordance with Helsinki declaration 
proposed by World Medical Association and subsequent amendments and 
approved by the Independent Ethics Committee (IEC) before implementation. 
Information and informed consent  
Ø All the patients who agree to participate should be asked to sign the 
informed consent form to prove their approval for participation in this study. 
The informed consent form must be signed and dated personally by the 
patients and investigators. 
Ø Before obtaining the informed consent, the investigators must provide 
sufficient information to the patients who are potential participants in this 
study:  
• The investigators should orally inform the patients of all the relevant 
circumstances of this study;  
• The information provided to patients must be fully and easily understood by 
non-professionals, so that they can make a decision according to their own 
willingness based on their full understanding of this study;  
• Additionally, the patients voluntarily participate in the study, and are free to 
quit from the study at any time, without any reasons. The subsequent 
treatment of patients is not under the influence of unwilling to participate or 
quitting from the study.  
Ø All the patients who agree to participate should be asked to sign the 
Informed Consent Form (ICF) to prove their approval for participation in this 
study. The ICF must be signed and dated personally by the patients and 
the investigators;  


Vision 3.0 
 
26
Ø The signed ICF will be kept in the Data Center and must be safely kept for 
future review at any time throughout the study. 
Withdrawal from the study  
The main withdrawal criteria are as following:  
Ø Relapsed during the first 4 weeks of treatment; 
Ø Changes in the patient’s condition after inclusion, which suggests that the 
study protocol is unsuitable for the patient;  
Ø Severe complications affecting the implementation of the study treatment;  
Ø Patients who are confirmed to require emergency treatment due to other 
diseases after inclusion;  
Ø Treatment unmated with the study protocol;  
Ø Patients who voluntarily quit or discontinue any examination, treatment and 
monitoring required by the study for personal reasons at any stage after 
inclusion in this study. The PI also has the right to withdraw patients from 
the study if he/she feels that the withdrawal is in the best interests of the 
patients. 
Identity and privacy of patients  
Ø After obtaining an ICF, each enrolled patient is assigned a subject number 
(allocation number). This number will represent the identity of the patient 
during the study and for the retrieving of dedicated clinical research 
database;  
Ø Throughout the study, several measures will be taken to minimize any 
breaches of personal information, including:  
• Only the PI and co-investigators will be able to link to the research data of 
the patients to themselves through the identifiable table after authorization;  
• Collection, transmission, handling and storage of the study data must 
comply with the data protection and privacy regulations. 


Vision 3.0 
 
27
Responsibility of independent ethics committee  
The responsibilities of independent ethics committee include: 
Ø Review of this study;  
Ø Evaluate this study to determine if risks to which patients are exposed have 
been duly minimized and whether these risks are reasonable compared to 
expected benefits;  
Ø Check the study protocol and relevant documents (patient information 
sheet, ICF, CRF, etc.) submitted by the Research Committee before 
beginning of the study;  
Ø Provide the written proof of ethical review opinions, the written proof of the 
date of the review meeting, the written proof of the members presenting at 
the meeting and voting members, the written proof of recording of the 
reviewed versions of study protocol, ICF and other related documents, and 
if possible, a copy of the minutes, to the Research Committee. The study 
can begin only after obtaining the written proof of favorable 
opinions/approval of the IEC;  
Ø Supervise the legitimacy of the process of informed consent;  
Ø Ensure the safety of patients during the research process by examining the 
reported safety information. The investigators should report to the IEC on 
any therapeutic complications which may affect the safety of patients. 
When complications that affect the patient safety occur, the IEC should 
inform PI to withdraw patients from the study and use any possible 
treatment to cure patients. If the PI decides not to withdraw patients from 
the study, he should provide a written proof of explanation to the IEC;  
Ø Review the reasonableness of the costs incurred by patients in the course 
of the study through a selective check for hospitalization expenses. When 
the patient has indications for off-label use of drugs, the IEC will receive the 
notice and the description of relevant situation from the investigators. The 
IEC should record the relevant records;  


Vision 3.0 
 
28
Ø Review the revisions of the study protocol, and any changes must be 
approved by the IEC before they are adopted. Unless the change is 
necessary to eliminate an immediate hazard to the patients, in which case 
the IEC should be informed as soon as possible;  
Ø Review the progress of the study annually and the close-out report 
submitted by the Research Committee at the end of the trial. 
Responsibility of investigator 
The responsibilities of investigators are as follows: 
Ø Investigators, participated in the clinical trial, should be obtained certificate 
for assistant practicing doctor, resigned and attended the training of the 
GCP guidelines and the correlation of laws and regulations, possessed 
specialty, qualification and ability in clinical trial. 
Ø Subjects are adequately recruited by the investigator during required time 
according to the clinical trial，and operation capacity and possibility to be 
qualified the item should be evaluated by the previous working experience.  
Ø Investigators are familiar with clinical trial protocols and execute instruction 
strictly according to the protocols and case report form. 
Ø In all adverse events, subjects must be taken appropriate therapies and 
made a contact with the investigator as soon as possible. Investigators will 
take responsibilities of relevant medical decision of clinical trial to ensure 
subjects that is taken adequate medical treatment. 
Ø Any information on the case report form possesses original data, to ensure 
the case history and case report form filled in truly, accurately, completely， 
timely, regularly and legally. 
Ø Subjects will be illustrated the relevant situation where the clinical trial is 
fully consent by Ethics Committee. The informed consent will be acquired 
and, during the process, it must meet the specification. 


Vision 3.0 
 
29
Ø Supervision and inspection will be received by supervisor and inspector 
assigned by sponsor to ensure the quality of clinical trial.  
Ø Any advices and suggestions focused on the study protocols might be 
submit to the principal institution of clinical research, and made a 
discussion with sponsor and coordination institutions to decide whether 
adopting the above advice or suggestions, during the clinical trial executed 
by each institutions.  
Publications 
Ø All the data collected during this study are the property of the study sponsor 
and cannot be communicated in any case to a third party without the written 
agreement of the investigator. 
Ø Any publication or communication (oral or written) will be decided from a 
common agreement between the investigators and will respect the 
international recommendations: "Uniforms Requirements for Manuscripts 
Submitted to Biomedical Journals" 
(http://www.cma.ca/publications/mwc/uniform.htm): notably, an authorship 
will be proposed to each clinical center participating in the study and to 
each member of the steering committee according to his/her actual 
participation. 
Organization and responsibility  
The Research Committee is responsible for developing study protocol, auditing 
patient eligibility and guiding interpretation of informed consent. It is also 
responsible for collection of complication reports, guiding diagnosis and 
treatment of complications and emergency intervention for serious 
complications, as well as approving the content and distribution of all 
publications related to the study. 


Vision 3.0 
 
30
Appendix  
Appendix 1. The score of bleeding 
Appendix 2. ECOG score 
Appendix 3. Criteria for IBMTR severity index for acute GVHD 
Appendix 4. NIH global severity of chronic GVHD 
Appendix 5. The table of study procedure 
Appendix 6. Patient consent form for study participation  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
31
Appendix 1. The score of bleeding* 
 
Grade  
Manifestation 
Score 0 
No bleeding. 
Score 1 
Occult bleeding in secretion, including mild petechia or minimal 
vaginal bleeding.  
Score 2 
Minor bleeding without the requirement of RBC transfusion, such 
as ecchymosis, epistaxis, line oozing, vaginal bleeding, skin 
bleeding, mild hematemesis, melena, mild hematuria. 
Score 3 
Bleeding that can cause a rapid fall of hematocrit and needs one 
or more units of RBC transfusion per day over the expected rate 
of an individual, or fail to obtain a post-transfusion increment at 
active bleeding. 
Score 4 
Life-threatening bleeding, defined as either massive bleeding 
causing severe hemodynamic compromise or bleeding into a 
vital organ, such as intracranial hemorrhage, pericardial 
hemorrhage, diffuse alveolar hemorrhage.  
Notes: RBC=red blood cell; *Nevo S, Enger C, Hartley E, et al. Acute bleeding and 
thrombocytopenia after bone marrow transplantation. Bone Marrow Transplant. 
2001;27(1):65-72. 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
32
Appendix 2. ECOG score* 
Grade 
Performance status 
0 
Fully active, able to carry on all pre-disease performance without 
restriction. 
1 
Able to move freely and take mild physical activity, such as 
housework and office work, but restricted in severe physical activity.  
2 
Able to move freely and take care of himself, but loss of work 
capability; doing activities for more than half of the waking hours. 
3 
Capable of taking care of himself partially, confined to the bed or chair 
for more than half of the waking hours.  
4 
Completely disabled, unable to take care of himself and totally 
confined to the bed or chair. 
5 
Dead 
 
Notes: ECOG=Eastern Cooperative Oncology Group; * Oken M, Creech R, Tormey D, et al. 
Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin 
Oncol. 1982;5:649-655. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
33
Appendix 3. Criteria for IBMTR severity index for acute GVHD* 
 
Skin involvement 
 
Liver involvement 
 
Gastrointestinal involvement 
Index 
Stage 
(max.) 
Rash 
range 
Stage 
(max.) 
Total bilirubin 
(μmol/L) 
 
Stage 
(max.) 
Volume of diarrhea 
(ml/d) 
A 
1 
<25% 
 
0 
<34 
 
0 
<500 
B 
2 
25%- 50% 
or 
1-2 
34-102 
or 
1-2 
550-1 500 
C 
3 
>50% 
or 
3 
103-255 
or 
3 
>1 500 
D 
4 
Bullae 
or 
4 
>255 
or 
4 
Severe pain and 
ileus 
 
Notes: GVHD=graft-versus-host disease; *Rowlings PA, Przepiorka D, Klein JP, et al. IBMTR 
Severity Index for grading acute graft-versus-host disease: retrospective comparison with 
Glucksberg grade. Br J Haematol. 1997;97(4):855-64. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
34
Appendix 4. Criteria of chronic GVHD* 
 
Severity  
Manifestation 
Mild 
1 or 2 Organs involved with no more than score 1 plus 
Lung score 0. 
Moderate 
3 or More organs involved with no more than score 1 
OR 
At least 1 organ (not lung) with a score of 2 
OR 
Lung score 1  
Severe 
At least 1 organ with a score of 3 
OR 
Lung score of 2 or 3  
Notes: GVHD=graft-versus-host disease; In skin: higher of the 2 scores to be used for 
calculating global severity. In lung: FEV1 is used instead of clinical score for calculating global 
severity. If the entire abnormality in an organ is noted to be unequivocally explained by a non-
GVHD documented cause, that organ is not included for calculation of the global severity. If 
the abnormality in an organ is attributed to multifactorial causes (GVHD plus other causes) 
the scored organ will be used for calculation of the global severity regardless of the 
contributing causes (no downgrading of organ severity score). * Jagasia MH, Greinix HT, 
Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for 
Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging 
Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Vision 3.0 
 
35
Appendix 5. The table of study procedure 
 


Vision 3.0 
 
36
 
Appendix 6: Patient consent form for study participation 
Title: Low-dose decitabine for refractory prolonged isolated 
thrombocytopenia after hematopoietic cell transplantation 
Investigator OR 
institution Name 
 
Study Site  
Patient Name 
 
Please tick each box below o if you have known the corresponding 
statement.    
                                    (to be completed by the patient) 
o What you should know about a research study  
Someone will explain this research study to you.  
Ø 
A research study is something you volunteer for.  
Ø 
Presence or absence of participation in the research study is up to you.  
Ø 
You can choose not to take part in the research study.  
Ø 
You can agree to take part now and later change your mind.  
Ø 
Whatever you decide it will not be held against you.  
Ø 
You can feel free to ask all the questions that you want before you decide . 
o What is the purpose of this study?  
Refractory prolonged isolated thrombocytopenia (RPIT), a frequent 
complication after hematopoietic stem cell transplantation (HCT), is 
associated with significantly adverse outcomes. It is urgent to explore 
effective agents that can promote the platelet recovery and prevent 
potentially fatal bleeding complications. We previously reported a pilot study 
which described the effectiveness of low-dose decitabine for increasing 
platelet counts in transplant recipients with RPIT by increasing the number 
of marrow megakaryocyte.  
To further validate the efficacy and safety of low-dose decitabine for RPIT and 
to preliminarily explore the potential mechanisms, this prospective, open-
label, three-arm, randomized clinical trial is conducted. 
o Why have I been chosen? 
We are inviting patients who 
Ø 
Platelet count < 30 × 109/L for more than 60 days post-HCT;  


Vision 3.0 
 
37
Ø 
Recovered neutrophil and hemoglobin concentrations;  
Ø 
Donor chimerism >95% detected by short-tandem repeat-polymerase 
chain reaction;  
Ø 
No response to conventional treatments for thrombocytopenia (rhTPO, 
immunoglobulin, rituximab and glucocorticoid, either alone or in 
combination) for a duration of at least 4 weeks. 
o Do I have to take part?  
Ø 
Participation in the study is entirely voluntary.  
Ø 
You will be given sufficient time to consider whether you want to participate 
in the study.  
Ø 
Non-participation in the study will not affect your future care that you will 
receive from your medical and nursing team in our hospital. 
Ø 
If you decide to join the study, you will be asked to sign an informed 
consent form.  
Ø 
You are free to withdraw from this research at any time and without giving 
a reason. Any of your current medical care and future treatment in our 
hospital will not be affected. 
o What will happen to me if I take part?  
All patients who agree to take part and provide a written informed consent form 
will be included into this study.  
If you are included in this research, you will be randomly assigned into the one of 
three treatment group. Randomization means that neither you nor your doctor will 
be able to select which treatment you will receive. We will use a computer to 
allocate you to one of this three groups with equal chances of each treatment 
approach being the one you will receive. This procedure will ensure that the 
number of patients in each of the three treatment groups is similar.  
Ø If you are assigned in the group A:  
You will be treated with decitabine (15 mg/m2 daily intravenously for 
consecutive 3 days (day 1 - day 3)) plus recombinant human thrombopoietin 
(300 U/kg.d from day 4 to day 28);  
Ø If you are assigned in the group B:  
You will be treated with decitabine alone (15 mg/m2 daily intravenously for 
consecutive 3 days); 
Ø If you are assigned in the group C: 
You will be treated with conventional treatments as usual. 


Vision 3.0 
 
38
Your doctors will introduce the detailed treatment procedures to you. You are 
free to ask any question about the treatments you may have. 
o How long will I be in the study 
If you participate in this study, you will receive  1  therapy for 4 weeks. 
Follow up will continue indefinitely, for as long as  6  months or longer. 
You can stop participating at any time. However, if you decide to stop 
participating in the study, we encourage you to talk to the researcher and 
your regular doctor first.  
o What are the risks of the study? 
Ø 
Potential adverse event of decitabine includes:  
• Myelosuppression: 
Neutropenia related infections, fever; 
Bleeding: ecchymosis, petechial, haematemesis, hemoptysis, melena, 
hematuresis, etc; 
Weary, somnolence, pale, etc (due to anemia); 
• Other non-hematological toxicity: 
Liver dysfunction; 
Renal dysfunction; 
• Drug allergy 
Erythra, edema, pruritus, swelling, etc 
Ø 
Potential adverse event of rhTPO includes:  
Thrombosis, injection site reaction (subcutaneous scleroma, fat atrophy, 
ache, etc), drug allergy. 
Ø 
Others: 
There also may be other unexpected complications or discomforts that we 
cannot predict.  
Your doctors will do their best to prevent complications and to treat them if 
occur. You will receive the best medical care available during and after the 
study and in the unlikely event of an injury arising from taking part in this 
study, you will be provided with the necessary care. 
oAre there benefits you to taking part in the study? 
You’ll get free treatment of rhTPO (Group A) and free test of blood and bone 
marrow (all participants). Another possible benefit you may experience from this 


Vision 3.0 
 
39
research includes recovery of your platelet level and prolongation of survival 
time. However, there is no guarantee that each patient will benefit from the 
treatment in this research.  
Furthermore, the results obtained from this study may be useful in guiding the 
treatment for patients with such disease in the future. 
o What are my responsibilities in this study?  
If you choose to take part in this study, you will need to:  
Ø 
Keep your study appointments.  
Ø 
Tell your doctor about:  
• All medications and supplements you are taking;  
• Any discomforts or complications you suspect;  
• Any doctors’ visits or hospital stays outside of this study;  
• Whether you have been or are currently in another research study.  
o How will my privacy be protected?  
Your health information, such as your response to cancer treatment, results of 
study tests, and medicines you took, will be kept by the data center of this 
research. This information is strictly confidential. However, your name and 
contact information will not be put in the database. If information from this study 
is published or presented at scientific meetings, there will be no personally 
identifiable information.  
o What happens if I change my mind during the study?  
We would certainly recommend that you continue the study, however, 
participation in the study is voluntary and you may stop the participation at any 
time that you wish without losing any of your rights as a patient here. Your 
treatment at our hospital will not be affected in any way. The PI of this study 
also has the right to withdraw patients from the study if he feels that the 
withdrawal is in your best interests. Your follow-up information will still be kept 
by doctor after you have stopped participating in the research. 
o Who is organizing the research?  
The study is organized by the The First Affiliated Hospital of Soochow 
University, Suzhou 215006, China. There are five other participating institutes 
including  Nanfang Hospital, Southern Medical University, Guangzhou 510515, 
China, Fujian Institute of Hematology, Fuzhou 350001, China, Children’s 
Hospital of Soochow University, Suzhou 215025, China, Hebei Yanda Lu 


Vision 3.0 
 
40
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Daopei Hospital, Langfang 065201, China and Rui Jin Hospital, Shanghai Jiao 
Tong University School of Medicine, Shanghai 200025, China. 
oWhom do I call if I have questions or problems? 
For information about your disease and research-related injury, you may 
contact:  
Name (institution) :                         Telephone Number:          
For information about this study, you may contact:  
Name (institution) :                         Telephone Number:          
For information about your rights as a research subject, you may contact:  
Name (institution) :                         Telephone Number:          


Vision 3.0 
 
41
Signature page 
 
 
 
I have read all the above, asked questions, and received answers 
concerning areas I did not understand. I have had the opportunity to take 
this consent form home for review or discussion.  
I willingly give my consent to participate in this program. Upon signing this 
form I will receive a copy. I may also request a copy of the protocol (full 
study plan).  
 
Patient 
signature  
 
Name 
(print) 
 
Date 
signed 
 
 
Investigator (institution) Statement and Signature  
to be completed by the person taking consent 
 
I have discussed this clinical research study with the patient and/or his or 
her authorized representative using a language that is understandable and 
appropriate. I believe that I have fully informed the participant of the nature 
of this study and the possible benefits and risks of taking part. I believe the 
participant has understood this explanation.  
 
Investigator OR 
institution signature 
 
Name 
(print) 
 
Date 
signed