Prospective Study of Patients With Thrombocytopenia Following HSCT

• Sponsor: The First Affiliated Hospital of Soochow University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02487563
• Collaborator: Peking University People's Hospital (Other), Nanfang Hospital of Southern Medical University (Other), Ruijin Hospital (Other), Wuhan Union Hospital, China (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)
• Enrollment: 97
• Location: 1
• Arms: 3
• Duration (Months): 42.3
• Patients Per Site Per Month: 2.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombocytopenia; Hematologic Diseases	Drug: Decitabine; Drug: rhTPO; Other: Conventional Treatment	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Study of Patients With Isolated Thrombocytopenia Following Hematopoietic Stem Cell Transplantation
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Apr 12, 2019
• Actual Study Completion Date: Apr 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Group 1 Decitabine in combination with rhTPO.	Drug: Decitabine; Decitabine; Other Names: 5-Aza-2'-deoxycytidine ; Drug: rhTPO; rhTPO; Other Names: Thrombopoietin
Experimental: Experimental Group 2 Decitabine	Drug: Decitabine; Decitabine; Other Names: 5-Aza-2'-deoxycytidine
Active Comparator: Control Group Conventional treatment except decitabine.	Other: Conventional Treatment; immunoglobulin, glucocorticoid etc

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Platelet Count Recovery [Up to 4 weeks after the treatment]

   Platelet response refers to a sustained increase (stable or increasing level) of at least 30×10E9/L independent of transfusion for 3 days.

Secondary Outcome Measures

1. Megakaryocyte Count [Up to 4 weeks after the treatment]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First affiliated Hospital of SooChow University	Suzhou	Jiangsu	China	215000

Sponsors and Collaborators

• The First Affiliated Hospital of Soochow University
• Peking University People's Hospital
• Nanfang Hospital of Southern Medical University
• Ruijin Hospital
• Wuhan Union Hospital, China
• Qilu Hospital of Shandong University
• Children's Hospital Of Soochow University
• Fujian Medical University Union Hospital
• Hebei Yanda Ludaopei Hospital

Investigators

• Study Chair: Depei Wu, PhD,MD, The First Affiliated Hospital of Soochow University

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Aug 7, 2017

More Information

Publications

None provided.

• Responsible Party: The First Affiliated Hospital of Soochow University
• ClinicalTrials.gov Identifier: NCT02487563
• Other Study ID Numbers: SOOCHOW-HY-2015
• First Posted: Jul 1, 2015
• Last Update Posted: May 6, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by The First Affiliated Hospital of Soochow University: Isolated thrombocytopenia; decitabine; rhTPO
• Additional relevant MeSH terms: Thrombocytopenia; Hematologic Diseases; Decitabine

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Experimental Group 1	Experimental Group 2	Control Group
Arm/Group Description	Decitabine in combination with rhTPO. Decitabine: Decitabine rhTPO: rhTPO	Decitabine Decitabine: Decitabine	Conventional treatment except decitabine. Conventional Treatment: immunoglobulin, glucocorticoid etc
Period Title: Overall Study
STARTED	32	33	32
COMPLETED	30	30	31
NOT COMPLETED	2	3	1

Baseline Characteristics

Arm/Group Title	Experimental Group 1	Experimental Group 2	Control Group	Total
Arm/Group Description	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.	Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3) alone.	Conventional therapies with recommended options including rhTPO, eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, alone or in combination.	Total of all reporting groups
Overall Participants	30	30	31	91
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	30	36	36	31
Sex: Female, Male (Count of Participants)
Female	5 16.7%	12 40%	15 48.4%	32 35.2%
Male	25 83.3%	18 60%	16 51.6%	59 64.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
China	30 100%	30 100%	31 100%	91 100%
Diagnosis (Count of Participants)
Acute lymphocytic leukemia	8 26.7%	10 33.3%	11 35.5%	29 31.9%
Acute myeloid leukemia	15 50%	14 46.7%	12 38.7%	41 45.1%
Chronic myeloid leukemia	0 0%	2 6.7%	1 3.2%	3 3.3%
Myelodyplastic syndrome	5 16.7%	4 13.3%	4 12.9%	13 14.3%
Non-Hodgkin lymphoma	2 6.7%	0 0%	3 9.7%	5 5.5%
Transplant Donor (Count of Participants)
Haploidentical donor	23 76.7%	20 66.7%	21 67.7%	64 70.3%
Matched related donor	5 16.7%	8 26.7%	6 19.4%	19 20.9%
Matched unrelated donor	2 6.7%	2 6.7%	4 12.9%	8 8.8%
ABO compatitibilty (Count of Participants)
ABO matched	15 50%	13 43.3%	18 58.1%	46 50.5%
ABO mismatched	15 50%	17 56.7%	13 41.9%	45 49.5%
Conditioning (Count of Participants)
Busulfan / cyclophosphamide	26 86.7%	27 90%	29 93.5%	82 90.1%
Others	4 13.3%	3 10%	2 6.5%	9 9.9%
Mononuclear cell infused (10E8/kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [10E8/kg]	9.78	10.50	9.40	10.04
Neutrophils recovery (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	12	12	13	12
Enrollment time (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	103	105	79	99
Platelet counts at enrollment (10E9 platelets/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [10E9 platelets/L]	14	12	17	15
Megakaryocyte counts at enrollment (cells/cm^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/cm^2]	2.9	3.2	3.1	3.0

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Platelet Count Recovery
Description	Platelet response refers to a sustained increase (stable or increasing level) of at least 30×10E9/L independent of transfusion for 3 days.
Time Frame	Up to 4 weeks after the treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Group 1	Experimental Group 2	Control Group
Arm/Group Description	Decitabine in combination with rhTPO. Decitabine: Decitabine rhTPO: rhTPO	Decitabine Decitabine: Decitabine	Conventional treatment except decitabine. Conventional Treatment: immunoglobulin, glucocorticoid etc
Measure Participants	30	30	31
Count of Participants [Participants]	20 66.7%	22 73.3%	6 19.4%

2. Secondary Outcome

Title	Megakaryocyte Count
Description	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.
Time Frame	Up to 4 weeks after the treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Group 1	Experimental Group 2	Control Group
Arm/Group Description	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.	Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3) alone.	Conventional therapies with recommended options including rhTPO, eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, alone or in combination.
Measure Participants	30	30	31
Median (Inter-Quartile Range) [cells/cm^2]	6.7	7.5	3.3

Adverse Events

Time Frame	Study period (4 weeks)
Arm/Group Title	Experimental Group 1		Experimental Group 2		Control Group
Arm/Group Description	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.		Decitabine 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3) alone.		Conventional therapies with recommended options including rhTPO, eltrombopag, immunoglobulin, rituximab, interleukin-11 and glucocorticoids, alone or in combination.
All Cause Mortality
	Experimental Group 1		Experimental Group 2		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/30 (0%)		1/31 (3.2%)
Serious Adverse Events
	Experimental Group 1		Experimental Group 2		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/30 (13.3%)		1/30 (3.3%)		3/31 (9.7%)
Blood and lymphatic system disorders
Bleeding events	1/30 (3.3%)		1/30 (3.3%)		0/31 (0%)
Cardiac disorders
Shock	1/30 (3.3%)		0/30 (0%)		1/31 (3.2%)
Infections and infestations
Infections	2/30 (6.7%)		0/30 (0%)		2/31 (6.5%)
Other (Not Including Serious) Adverse Events
	Experimental Group 1		Experimental Group 2		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/30 (26.7%)		5/30 (16.7%)		7/31 (22.6%)
Blood and lymphatic system disorders
Bleeding events	3/30 (10%)		2/30 (6.7%)		3/31 (9.7%)
Cardiac disorders
Chest distress	1/30 (3.3%)		1/30 (3.3%)		0/31 (0%)
Eye disorders
Blurred vision	0/30 (0%)		1/30 (3.3%)		0/31 (0%)
Gastrointestinal disorders
Anorexia	1/30 (3.3%)		0/30 (0%)		0/31 (0%)
Nausea	1/30 (3.3%)		0/30 (0%)		0/31 (0%)
General disorders
Fatigue	2/30 (6.7%)		1/30 (3.3%)		1/31 (3.2%)
Hepatobiliary disorders
Hypohepatia	2/30 (6.7%)		1/30 (3.3%)		1/31 (3.2%)
Infections and infestations
Fever	1/30 (3.3%)		2/30 (6.7%)		1/31 (3.2%)
Infection	0/30 (0%)		0/30 (0%)		1/31 (3.2%)
Metabolism and nutrition disorders
Hypeluricemia	0/30 (0%)		1/30 (3.3%)		0/31 (0%)
Nervous system disorders
Headache	1/30 (3.3%)		0/30 (0%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Erythra	0/30 (0%)		1/30 (3.3%)		1/31 (3.2%)

Limitations/Caveats

Small number of patients, the diversity of patients, and the heterogeneous treatment options in Arm C.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.