MSCs With or Without Peripheral Blood Stem Cell for Treatment of Poor Graft Function and Delayed Platelet Engraftment

Phase 2

• Conditions: Stem Cell Transplantation, Hematopoietic; Hematological Diseases; Poor Graft Function; Delayed Platelet Engraftment
• Interventions: Biological: PBSC; Biological: MSCs

• Registration Number: NCT02240992
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

The purpose of this study is to compare the efficacy of mesenchymal stem cells (MSCs) with or without granulocyte colony-stimulating factor (G-CSF) mobilized peripheral stem cells (PBSC) in treating patients experiencing poor graft function or delayed platelet engraftment after allogeneic hematopoietic stem cell transplantation.

Detailed Description

Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the only cure for many hematologic diseases. However, about 5-27% of patients would suffer from poor graft function (PGF) and more recipients might develop delayed platelet engraftment (DPE) after allo-HSCT. These complications are associated with considerable mortality related to infections or hemorrhagic complications. Treatment of PGF and DPE usually involves hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO), or second transplantation, but these methods have dismal effect or even a significant risk of graft-versus-host disease (GVHD).

Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs include improving hematopoietic engraftment, preventing and treating graft-versus-host disease after allo-HSCT and so on. Some studies have shown that MSCs combined with PBSC or cord blood could be useful to improve engraftment after HSCT. Several reports suggested MSCs might be effective in the treatment of PGF.

However, the efficacy of MSCs as single-drug treatment for PGF or DPE is unsatisfactory in our previous study. Therefore, in the present study, G-CSF mobilized PBSC will be used combined with MSCs in the patients with PGF or DPE after allo-HSCT.

Study Timeline

• Status Verified: 2014-09
• Study Start: 2014-09
• Study First Submitted: 2014-09-13
• Study First Submitted QC: 2014-09-13
• Last Update Submitted: 2014-09-13
• Study First Posted: 2014-09-16
• Last Update Posted: 2014-09-16
• Primary Completion: 2018-09
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Age：14-65 years
• PGF or DPE after allo-HSCT
• Subjects (or their legally acceptable representatives) must have signed an informed consent document

Exclusion Criteria

• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSCs&PBSC	MSCs	PBSC will be intravenously infused at a dose of 2×10\^8/kg. MSCs will be intravenously infused at a dose of 1×10\^6 cells/kg once per week or until complete response(CR) . If the patients do not achieve CR or partial remission (PR) within 4 weeks, they will swithed to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.
MSCs	MSCs	MSCs will be intravenously infused at a dose of 1×10\^6 cells/kg once per week or until CR. If the patients have no response (NR) within 4 weeks, they will switch to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.
MSCs&PBSC	PBSC	PBSC will be intravenously infused at a dose of 2×10\^8/kg. MSCs will be intravenously infused at a dose of 1×10\^6 cells/kg once per week or until complete response(CR) . If the patients do not achieve CR or partial remission (PR) within 4 weeks, they will swithed to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Hematopoietic Recovery	1 year	Hematopoietic reconstitution post-transplantation is defined as reconstitution of both neutrophil and platelet numbers. Neutrophil reconstitution is defined as occurring on the first 3 consecutive days with an neutrophil(NEU)\>0.5×10\^9/L, and platelet (PLT) reconstitution is defined as the first \>20×10\^9/L for 3 consecutive days.

Secondary Outcome Measures

Name	Time	Method
Incidence of graft-versus-host disease	1 year	Graft-versus-host disease (GVHD) includes acute GVHD and chronic GVHD.
Incidence of infections	1 year	Infections include bacterial, invasive fungal and viral infections
Incidence of primary underlying disease relapse	1 year
Incidence of acute toxicity	up to 100 days	Acute toxicity mainly involves the heart,live and kidney.

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China