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Peripheral Blood Stem Cell Combined With Mesenchymal Stem Cells for Treatment of Poor Graft Function

Phase 2
Conditions
Stem Cell Transplantation, Hematopoietic
Hematological Diseases
Poor Graft Function
Interventions
Biological: PBSC
Biological: MSCs
Registration Number
NCT02083718
Lead Sponsor
Nanfang Hospital, Southern Medical University
Brief Summary

The purpose of this study is to evaluate the utility of treating patients experiencing poor graft function after allogeneic hematopoietic stem cell transplantation with Granulocyte Colony-Stimulating Factor (G-CSF) mobilized peripheral stem cell combined (PBSC) with ex-vivo-expanded BM-drived mesenchymal stem cells from third-party donors. Our first objective was to evaluate the effect of such treatment on poor graft function, and second object was to investigate the safety of such treatment.

Detailed Description

Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the only cure for many hematologic diseases. However, poor graft function (PGF) is an important complication after allo-HSCT that occurs in 5-27% of patients, and is associated with considerable mortality related to infections or hemorrhagic complications. Treatment of PGF usually involves the prescription of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF), or second transplantation, but these methods are associated with 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 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 after allo-HSCT.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
Inclusion Criteria
  • A patient age of 14-65 years
  • Poor graft function developing after allo-HSCT
  • Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
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
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PBSC & MSCsPBSCPBSC 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. The vital signs of all patients will be closely monitored during and for 24h after administration.If the NEU and PLT levels do not attain the completely response(CR)standards within 28d, a second course of the same treatment will be given.
PBSC & MSCsMSCsPBSC 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. The vital signs of all patients will be closely monitored during and for 24h after administration.If the NEU and PLT levels do not attain the completely response(CR)standards within 28d, a second course of the same treatment will be given.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Hematopoietic Recovery1 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
NameTimeMethod
Number of Participants with Serious and Non-Serious Adverse Eventsup to 1 year

Adverse Events include infections, GVHD, primary underlying disease relapse and any other side effects. Infections will be mainly focused within the first 100 days after treatment. Side effects of treatment includes acute toxicity and late side effects. Acute toxicity principally involves the heart,live and kidney. Late toxic side effects involves principally the development of secondary tumors and relapse of the primary disease.

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

🇨🇳

Guangzhou, Guangdong, China

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