Megakaryocytic Progenitor Cells for Prophylaxis and Treatment of Thrombocytopenia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of ex vivo generated megakaryocytic progenitor cells (MPs) in prophylaxis and treatment of thrombocytopenia caused by chemotherapy in patients with acute leukemia (AL).

Detailed Description
-----------------
Thrombocytopenia is a common and potentially fatal complication of chemotherapy and hematopoietic stem cell transplantation. Owing to the short storage time and increased demand of platelets from unrelated donors, a constant shortage in the supply of platelets has become an important medical and society challenge. Therefore, investigation of alternative sources of platelets would be beneficial. Hematopoietic stem cells (HSCs) can be used to generate functional megakaryocytic progenitors (MPs), megakaryocytes, and platelets on a large scale. Functional MPs and platelets have successfully been produced in vitro from CD34+ hematopoietic cells from bone marrow, cord blood, and peripheral blood. Several studies have reported that transplantation of in vitro auto-producing MPs can promote platelet recovery after high-dose therapy and HSC transplantation. Umbilical cord blood is an abundant source of HSCs. In vitro large scale production of MPs from cord blood could represent an effective platelet substitute. Theoretically, the additional transplantation of ex vivo generated progenitor and post-progenitor cells might lead to the production of sufficient numbers of mature functional cells within a few days after transplantation.

Official Title
-----------------
Megakaryocytic Progenitor Cells for Prophylaxis and Treatment of Thrombocytopenia in Patients With Acute Leukemia Receiving Chemotherapy

Conditions
-----------------
Hematological Diseases, Thrombocytopenia

Intervention / Treatment
-----------------
* Biological: MPs
* Drug: thrombopoietin (TPO) and interleukin-11


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age：14-65 years achieve complete remission of acute leukemia the first course of consolidation chemotherapy ECOG grades 0 or 1 expected survival time ≥ three months Subjects (or their legally acceptable representatives) must have signed an informed consent document. Exclusion Criteria: cardiac dysfunction (particularly congestive heart failure), hepatic abnormalities (bilirubin ≥ 3 mg/dL, aminotransferase> 2 times the upper limit of normal), renal dysfunction (creatinine clearance rate < 30 mL/min) Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Patients with any conditions not suitable for the trial (investigators' decision)

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MPs<br>MPs will be intravenously infused within 48 hours after chemotherapy. During the study period, patients can receive platelet infusion but can not receive platelet stimulating factors. | Biological: MPs<br>* MPs are generated from cord blood using a combination of cytokines.<br>|
| Active Comparator: Non-MPs<br>Patients can receive platelet infusion but can not receive platelet stimulating factors. | Drug: thrombopoietin (TPO) and interleukin-11<br>* Platelet stimulating factors include thrombopoietin (TPO) and interleukin-11 and so on.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet recovery after infusion of MPs | Platelet recovery after infusion of MPs includes the time from infusion to platelet count≥20×10^9/L,50×10^9/L,100×10^9/L. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency of platelet infusion |  | 3 months | 
| incidence of acute toxicity | Acute toxicity mainly involves the heart,live and kidney. | 3 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Megakaryocytic Progenitor Products, Hematological Diseases, Thrombocytopenia