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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Nanfang Hospital of Southern Medical University
Sponsor:
Collaborators:
First Affiliated Hospital, Sun Yat-Sen University
Third 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
Guangdong Provincial People's Hospital
Southern Medical University, China
Information provided by (Responsible Party):
Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier:
NCT01379391
First received: June 20, 2011
Last updated: October 29, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Myeloablative
Delayed Platelet Engraftment
Drug: Recombinant Human Thrombopoietin

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
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

Further study details as provided by Nanfang Hospital of Southern Medical University:

Primary Outcome Measures:
  • Total Response Rate to TPO [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

    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. Non response: PLT <20G/L on +28 day after completing the 14-day course.



Secondary Outcome Measures:
  • Proportion of Adverse Events related to TPO [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Number and Proportion of Participants with Adverse Events or Severe Adverse Events related to TPO,are selected for measuring safety of TPO intervention on patients with delayed platelet engraftment after Allo-HSCT.


Biospecimen Retention:   Samples Without DNA

Peripheral blood and bone marrow samples for CFU-MK culture, FACS analysis.


Estimated Enrollment: 60
Study Start Date: June 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Delayed Platelet Engraftment, Allo-HSCT
Patients received myeloablative Allo-HSCT with platelet lower than 20G/L on +14d post-transplantation.
Drug: Recombinant Human Thrombopoietin

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.


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients received myeloablative allogeneic hematopoietic stem cell transplantation and the platelet count is lower than 20G/L +14d post-transplant.

Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01379391

Contacts
Contact: Hongsheng Zhou, PhD MD 86-20-62787883 hanson2008@gmail.com

Locations
China, Guangdong
Guangzhou Overseas Chinese Hospital,Guangdong Recruiting
Guangzhou, Guangdong, China, 510630
Contact: Kanger Zhu, MD       tzhuker@jnu.edu.cn   
Principal Investigator: Kanger Zhu, MD         
Guangdong General Hospital Recruiting
Guangzhou, Guangdong, China, 510030
Contact: Suijin Wu, MD       songwu55555@163.com   
Principal Investigator: Suijin Wu, MD         
Guangdong No.2 Provincial People's Hospital Recruiting
Guangzhou, Guangdong, China, 510317
Contact: Qing Zhang, MD       zhqing@vip.163.com   
Principal Investigator: Qing Zhang, MD         
Guangzhou General Hospital of Guangzhou Military Command Recruiting
Guangzhou, Guangdong, China, 510010
Contact: Yang Xiao, MD       jdxiao111@163.com   
Principal Investigator: Yang Xiao, MD         
Zhujiang Hospital of Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510282
Contact: Yuhua Li, MD PhD       li_yuhua@yahoo.com   
Principal Investigator: Yuhua Li, MD PhD         
Nanfang Hospital Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Hongsheng Zhou, MD PhD    86-20-62787883    hanson2008@gmail.com   
Sub-Investigator: Hongsheng Zhou, MD PhD         
Sub-Investigator: Qifa Liu, MD         
Sub-Investigator: Guopan Yu, MD         
Sub-Investigator: Xian Zhang, MD         
Sub-Investigator: Feng Huang, MD         
Sub-Investigator: Mo Yang, PhD MD         
Sub-Investigator: Fanyi Meng, MD         
Third Affiliated Hospital, Sun Yat-Sen University Recruiting
Guangzhou, Guangdong, China, 510630
Contact: Dongjun Lin, MD       lindongjun0168@163.com   
Principal Investigator: Dongjun Lin, MD         
First Affiliated Hospital, Sun Yat-Sen University Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Duorong Xu, MD       xudr@hotmail.com   
Principal Investigator: Duorong Xu, MD         
Zhongshan People Hospital,Guangdong Recruiting
Zhongshan, Guangdong, China, 528403
Contact: Xiaojun Xu, MD       doctorxu@163.com   
Principal Investigator: Xiaojun Xu, MD         
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
First Affiliated Hospital, Sun Yat-Sen University
Third 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
Guangdong Provincial People's Hospital
Southern Medical University, China
Investigators
Principal Investigator: Jing Sun, MD Department of Hematology, Nanfang Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT01379391     History of Changes
Other Study ID Numbers: TPO-HSCT-2011
Study First Received: June 20, 2011
Last Updated: October 29, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Nanfang Hospital of Southern Medical University:
Allogeneic Hematopoietic Stem Cell Transplantation
Platelet Engraftment
TPO

ClinicalTrials.gov processed this record on October 23, 2014