Megakaryocytic Progenitor Cells for Prophylaxis and Treatment of Thrombocytopenia

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

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).

Study Overview

• Status: Unknown
• Conditions: Thrombocytopenia; Hematological Diseases
• Intervention / Treatment: Biological: MPs; Drug: thrombopoietin (TPO) and interleukin-11

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.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MPs; 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; MPs are generated from cord blood using a combination of cytokines.
Active Comparator: Non-MPs; Patients can receive platelet infusion but can not receive platelet stimulating factors.	Drug: thrombopoietin (TPO) and interleukin-11; Platelet stimulating factors include thrombopoietin (TPO) and interleukin-11 and so on.

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

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Peking University People's Hospital; Sun Yat-sen University; Guangzhou First People's Hospital; Huazhong University of Science and Technology; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Guangdong Provincial People's Hospital; Third Affiliated Hospital, Sun Yat-Sen University; Guangzhou General Hospital of Guangzhou Military Command; Southern Medical University, China; Academy Military Medical Science, China

Publications and helpful links

General Publications

• Xi J, Zhu H, Liu D, Nan X, Zheng W, Liu K, Shi W, Chen L, Lv Y, Yan F, Li Y, Xie X, Wang Y, Yue W, Xu X, Wei X, Zhu J, Huang X, Pei X. Infusion of megakaryocytic progenitor products generated from cord blood hematopoietic stem/progenitor cells: results of the phase 1 study. PLoS One. 2013;8(2):e54941. doi: 10.1371/journal.pone.0054941. Epub 2013 Feb 4.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): September 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: September 13, 2014
• First Submitted That Met QC Criteria: September 15, 2014
• First Posted (Estimate): September 16, 2014

Study Record Updates

• Last Update Posted (Estimate): September 16, 2014
• Last Update Submitted That Met QC Criteria: September 15, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Thrombocytopenia; Hematological Diseases; Megakaryocytic Progenitor Products
• Additional Relevant MeSH Terms: Blood Platelet Disorders; Hematologic Diseases; Thrombocytopenia; Antineoplastic Agents; Oprelvekin
• Other Study ID Numbers: MPs-AL-2014