Clinical trial NCT01379391: Efficacy and Safety of rHuTPO on Platelet Engraftment After Allo-HSCT
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Myeloablative
Delayed Platelet Engraftment
Keywords: Allogeneic Hematopoietic Stem Cell Transplantation
Platelet Engraftment
TPO
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Guangdong Provincial People's Hospital
name: Guangdong No.2 Provincial People's Hospital
name: Guangzhou General Hospital of Guangzhou Military Command
name: Guangzhou Overseas Chinese Hospital,Guangdong
name: Zhongshan People's Hospital, Guangdong, China
name: Southern Medical University, China
First posted: 2011-06-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Total Response Rate to TPO
timeFrame: 4 weeks
Secondary outcomes:
measure: Transplantation Related Mortality (TRM)
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou General Hospital of Guangzhou Military Command
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: First Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong No.2 Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Overseas Chinese Hospital,Guangdong
state: Guangdong
city: Guangzhou
country: China
facility: Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan People Hospital,Guangdong
state: Guangdong
Study officials:
affiliation: Department of Hematology, Nanfang Hospital
name: Jing Sun, MD
role: PRINCIPAL_INVESTIGATOR
References: