Mesenchymal Stem Cells Combined With Cord Blood for Treatment of Graft Failure

Hematopoietic Stem Cell Transplantation Clinical Trial

Official title:

Mesenchymal Stem Cells Combined With Cord Blood for Treatment of Graft Failure Following Autologous Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01763099
• Other study ID #: NFH-MSC-auto-HSCT-2013
• Status: Recruiting
• Phase: Phase 2
• First received: January 5, 2013
• Last updated: January 15, 2013
• Start date: January 2013
• Est. completion date: January 2016

Study information

• Verified date: January 2013
• Source: Nanfang Hospital of Southern Medical University
• Contact: Ren Lin, MD
• Phone: +86-020-61641613
• Email: lansinglinren[@]hotmail.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the utility of treating patients experiencing graft failure after autologous hematopoietic stem cell transplantation with ex-vivo-expanded BM-drived mesenchymal stem cells from third-party donors or mesenchymal stem cells combined with cord blood. The first objective of this study was to evaluate the effect of such treatment on graft failure, and second object was to investigate the safety of such treatment.

Description:

Autologous hematopoietic stem cell transplantation (auto-HSCT) are considered the standard of care for many malignancies, such as lymphoma, myeloma and some leukemias, and so on. Graft failure after auto-HSCT is a formidable complication. It occurs in 2-9.5% of patients and is associated with considerable morbidity and mortality related to infections and hemorrhagic complications. There are various options for the management of graft failure. The most common treatment of graft failure is growth factors such as granulocyte colony-stimulating factor (G-CSF)and recombinant erythropoietin,but it usually effective in the short term and no effect on platelet counts.

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 are evolving rapidly with goals of improving hematopoietic engraftment, preventing and treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation and so on.As an important source of hematopoietic stem cell, cord blood has been widely used in clinical practice. It is reported that cord blood combined with MSCs can increase engraftment after allogeneic hematopoietic stem cell transplantation. However, to our knowledge, the report about efficacy of treatment of graft that develops after auto-HSCT using expanded BM-derived MSCs from a third-party donor combined with cord blood is absent.If such treatment could be shown to be effective and safe, BM-derived MSCs could potentially be used as an universal donor material. This would have a major impact because the generation of donor-specific MSCs is time-consuming, costly, and often impractical if the clinical status of a patient is urgent.

In the present study, the investigators will prospectively evaluate the efficacy and safety of ex-vivo-expanded BM-derived MSCs from third-party donors or MSCs combined with cord blood in treating patients with graft failure after auto-HSCT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2016
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

• A patient age of 14-65 years

• Graft failure developing after auto-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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Failure
• Hematologic Diseases
• Hematological Diseases
• Hematopoietic Stem Cell Transplantation
• Mesenchymal Stem Cells
• Umbilical Cord Blood

Intervention

Biological:
• Mesenchymal stem cells
Mesenchymal stem cells will be intravenously infused via a central venous catheter(at a dose of 1×10^6 cells/kg, over 15 min) in day 1 and day 15 of the cycle. If the NEU and PLT levels do not attain the completely response(CR)standards after this cycle, mesenchymal stem cells combined with cord blood will be given. If the NEU and PLT levels attain the completely response(CR)or partly response(PR) standards after this cycle, another cycle with the same strategy will be given.
• Mesenchymal stem cells and cord blood
Mesenchymal stem cells will be given (at a dose of 1×10^6 cells/kg,intravenously infused via a central venous catheter)on day 1.day 15, day 29 and day 43 of the cycle. Cord blood will be given intravenously infused via a central venous catheter on day 2 of the cycle.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (10)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	Guangdong General Hospital, Guangzhou First Municipal People’s Hospital, Guangzhou General Hospital of Guangzhou Military Command, Peking University People's Hospital, Southern Medical University, China, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Sun Yat-sen University, Third Affiliated Hospital, Sun Yat-Sen University, Zhongshan People's Hospital, Guangdong, China

Country where clinical trial is conducted

China, 

References & Publications (2)

Koç ON, Lazarus HM. Mesenchymal stem cells: heading into the clinic. Bone Marrow Transplant. 2001 Feb;27(3):235-9. Review. — View Citation

Smith AR, Wagner JE. Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord blood. Br J Haematol. 2009 Oct;147(2):246-61. doi: 10.1111/j.1365-2141.2009.07828.x. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hematopoietic recovery	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.	1 year	No
Secondary	infections, primary underlying disease relapse and any toxic side effects of MSCs treatment	Infections will be mainly focused within the first 100 days after MSCs treatment. Toxic 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.	1 year	Yes