Efficacy and Safety of rHuTPO on Platelet Engraftment After Allo-HSCT

Phase 4

• Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Myeloablative; Delayed Platelet Engraftment
• Interventions: Drug: Recombinant Human Thrombopoietin (rHTPO)

• Registration Number: NCT01379391
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

Factors influencing platelet engraftment after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) includes previous chemotherapy courses, conditioning regimen, HLA compatibility, source of stem cell, CD34+ cell count, infection of virus/bacteria/fungal, graft-versus-host disease (GVHD), etc. Large-scaled clinical trials have demonstrated that platelet count below 20G/L on 14 days after transplantation is an predictive factor for delayed platelet engraftment, which lead to increased platelet infusion requirement and high risk of bleeding. Multivariable survival analysis indicated that delayed platelet engraftment in Allo-HSCT is independent predictive factor for transplantation related mortality (TRM). But effective treatment approaches for delayed platelet recovery after Allo-HSCT are still lacking now.

Recombinant human thrombopoietin (rHuTPO) is a fully modified recombinant human thrombopoietin accurately expressed in mammalian cells. The rHuTPO agent manufactured by the 3Bio Pharmaceutical Limited Liability Company (LLC) in Shenyang is approved by the State Food and Drug Administration (SFDA) of China in 2005 and is the first rHuTPO agent available globally. RHuTPO was approved for for immune thrombocytopenia and chemotherapy-related thrombocytopenia in China. Animal experiments showed that TPO-mobilizing stem cell could promote platelet engraftment in Allo-HSCT in mice. As for efficacy and safety of TPO on platelet engraftment after Allo-HSCT, it's marginally addressed in clinical trials.

Based on preliminary research results, investigator designed a phase IV, open-label, prospective, multicenter Study of the efficacy and safety of recombinant human thrombopoietin injection (rHuTPO, TPIAO)on platelet engraftment in Allo-HSCT in China.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2011-06-20
• Study First Submitted QC: 2011-06-21
• Study First Posted: 2011-06-23
• Status Verified: 2015-09
• Primary Completion: 2015-09
• Last Update Submitted: 2015-10-07
• Last Update Posted: 2015-10-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Ages: 18 years to 65 years.
2. Patients received myeloablative allogeneic hematopoietic stem cell transplantation from related or non-related, HLA compatible or incompatible donors. History controls or concurrent controls are used.
3. The platelet count is lower than 20G/L on +14d post-transplant .
4. The informed consent form has been signed.
5. The following exclusion criteria are excluded.

Exclusion Criteria

1. Patients received non-myeloablative hematopoietic stem cell transplantation.
2. Patients with severe cardio-cerebral diseases with over grade III A YHA cardiac function or with past history of coronary heart disease, cerebral thrombosis, cerebral arteriosclerosis, etc.
3. Patients with severe hepatic or renal dysfunction with more than 5 times the upper limit of normal range (ULN) of serum ALT or AST levels, or with more than 5 times the upper limit of normal range (ULN) of serum TBIL level or less than 40% of normal prothrombin time activity (PTA); or with more than 3 times the ULN of serum Cr.
4. Patients with history of deep vein thrombosis within 8 weeks of enrollment.
5. Patients with hepatic obstructive venous disease without recovery within 2 weeks of enrollment.
6. Patients with thrombotic microangiopathy without recovery within 2 weeks of enrollment.
7. Patients with capillary leaking syndrome without recovery within 2 weeks of enrollment.
8. Patients with other conditions considered unsuitable for the study.
9. Patients with hypercoagulopathy condition with two or more of these criteria: INR lower than 0.82, APTT lower than the lower limit of normal values (23 seconds) or PT lower than the lower limit of normal values (10 seconds).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TPO	Recombinant Human Thrombopoietin (rHTPO)	Patients received myeloablative Allo-HSCT with platelet lower than 20G/L on +14d post-transplantation. Patient enrolled in TPO arm will recieved Recombinant Human Thrombopoietin (rHTPO) treatment fro 14 days.

Primary Outcome Measures

Name	Time	Method
Total Response Rate to TPO	4 weeks	Response Rate is selected as primary outcome for measuring efficacy of TPO for patients with delayed platelet engraftment after Allo-HSCT.; Markedly response: Platelet count of more than 50G/L in complete blood count on +28d post-transplantation after finishing 14-day course of TPO intervention, or PLT≥100G/L within the 14-day course.; Response: PLT 20-50G/L on +28 day after completing the 14-day course. No response: PLT \<20G/L on +28 day after completing the 14-day course.

Secondary Outcome Measures

Name	Time	Method
Transplantation Related Mortality (TRM)	1 year	Transplantation related mortality (TRM) in two arms after Allo-HSCT.

Trial Locations

Locations (9)

Guangzhou General Hospital of Guangzhou Military Command; 🇨🇳 Guangzhou, Guangdong, China

Zhongshan People Hospital,Guangdong; 🇨🇳 Zhongshan, Guangdong, China

Guangdong No.2 Provincial People's Hospital; 🇨🇳 Guangzhou, Guangdong, China

Nanfang Hospital; 🇨🇳 Guangzhou, Guangdong, China

Zhujiang Hospital of Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

Guangdong General Hospital; 🇨🇳 Guangzhou, Guangdong, China

First Affiliated Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China

Third Affiliated Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China

Guangzhou Overseas Chinese Hospital,Guangdong; 🇨🇳 Guangzhou, Guangdong, China