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

Allogeneic Hematopoietic Stem Cell Transplantation Clinical Trial

— TPO  

Official title:

A Phase IV, Open-label, Prospective, Multicenter Study of the Efficacy and Safety of Recombinant Human Thrombopoietin Injection (rHuTPO, TPIAO)on Platelet Engraftment in Allogeneic Hematopoietic Stem Cell Transplantation in China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01379391
• Other study ID #: TPO-HSCT-2011
• Status: Recruiting
• Phase: Phase 4
• First received: June 20, 2011
• Last updated: October 7, 2015
• Start date: June 2010

Study information

• Verified date: September 2015
• Source: Nanfang Hospital of Southern Medical University
• Contact: Hongsheng Zhou, PhD MD
• Phone: 86-20-62787883
• Email: hanson2008[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Stem Cell Transplantation
• Delayed Platelet Engraftment
• Myeloablative

Intervention

Drug:
• Recombinant Human Thrombopoietin (rHTPO)
Patients received allogeneic myeloablative hematopoietic stem cell transplantation with platelet count lower than 20G/L on +14 days after Allo-HSCT, met the above enrollment criteria and signed the informed consent forms are eligible subjects. Administration method of rHuTPO: 300U/kg/d by percutaneous injection; Timing: d14 to d28 after Allo-HSCT.

Locations

Country	Name	City	State
China	First Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Guangdong No.2 Provincial People's Hospital	Guangzhou	Guangdong
China	Guangzhou General Hospital of Guangzhou Military Command	Guangzhou	Guangdong
China	Guangzhou Overseas Chinese Hospital,Guangdong	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Zhongshan People Hospital,Guangdong	Zhongshan	Guangdong

Sponsors (9)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	First Affiliated Hospital, Sun Yat-Sen University, Guangdong General Hospital, Guangdong No.2 Provincial People's Hospital, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou Overseas Chinese Hospital,Guangdong, Southern Medical University, China, Third Affiliated Hospital, Sun Yat-Sen University, Zhongshan People's Hospital, Guangdong, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Response Rate to TPO	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.	4 weeks	Yes
Secondary	Transplantation Related Mortality (TRM)	Transplantation related mortality (TRM) in two arms after Allo-HSCT.	1 year	Yes

External Links

•   Website of Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.