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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Allogeneic Hematopoietic Stem Cell Transplantation, Myeloablative, Delayed Platelet Engraftment

Intervention / Treatment
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* Drug: Recombinant Human Thrombopoietin (rHTPO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages: 18 years to 65 years. 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. The platelet count is lower than 20G/L on +14d post-transplant . The informed consent form has been signed. The following exclusion criteria are excluded. Exclusion Criteria: Patients received non-myeloablative hematopoietic stem cell transplantation. 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. 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. Patients with history of deep vein thrombosis within 8 weeks of enrollment. Patients with hepatic obstructive venous disease without recovery within 2 weeks of enrollment. Patients with thrombotic microangiopathy without recovery within 2 weeks of enrollment. Patients with capillary leaking syndrome without recovery within 2 weeks of enrollment. Patients with other conditions considered unsuitable for the study. 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TPO<br>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. | Drug: Recombinant Human Thrombopoietin (rHTPO)<br>* 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.<br>|
| No Intervention: TPO-Free Arm<br>No TPO intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplantation Related Mortality (TRM) | Transplantation related mortality (TRM) in two arms after Allo-HSCT. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TPO, Allogeneic Hematopoietic Stem Cell Transplantation, Platelet Engraftment