MSCs Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant aGVHD

Acute Graft-versus-host Disease Clinical Trial

Official title:

Mesenchymal Stem Cells Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02241018
• Other study ID #: NFH-MSC-aGVHD-2014
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: September 13, 2014
• Last updated: September 13, 2014
• Start date: September 2014
• Est. completion date: December 2018

Study information

• Verified date: September 2014
• Source: Nanfang Hospital of Southern Medical University
• Contact: Ren Lin
• Phone: +86-020-62787883
• 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 compare the efficacy of CD25 monoclonal antibody and calcineurin inhibitors with or without mesenchymal stem cells (MSCs) in treating patients with steroid-resistant acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation.

Description:

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for several hematological disorders. Although good progress has been made in the prevention and treatment of side effects associated with transplantation, aGVHDremains a common and life-threatening complication with poor prognosis. Corticosteroids are still acted as the first-line treatments of aGVHD, with a response rate of 50-80. However, those who failed to initial therapy only have 10-30% long-term survival.

Mesenchymal stromal cells (MSCs) are a form of multipotent adult stem cells that can be isolated from many tissues, such as bone marrow (BM), adipose tissue and umbilical cord. Such cells possess the capacity to suppress immunological responses, support hematopoiesis and repair tissues. Clinical applications of human MSCs are evolving rapidly for preventing and treating GVHD. Although the results are still controversy, most prospective and retrospective data suggest that MSCs are effective to aGVHD.

In the present study, the investigators will prospectively evaluate the efficacy and safety of ex-vivo-expanded BM-derived MSCs from third-party donors combined with CD25 monoclonal antibody and calcineurin inhibitors in treating patients with aGVHD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

• age of 14-65 years

• steroid-resistant aGVHD

• 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

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

Related Conditions & MeSH terms

• Acute Graft-versus-host Disease
• Graft vs Host Disease

Intervention

Drug:
• CD25 monoclonal antibody

• calcineurin inhibitors

Biological:
• MSCs

Locations

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

Sponsors (11)

Lead Sponsor

Collaborator

Nanfang Hospital of Southern Medical University

Academy Military Medical Science, China, Guangdong General Hospital, Guangzhou First Municipal People’s Hospital, Guangzhou General Hospital of Guangzhou Military Command, Huazhong University of Science and Technology, 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

Country where clinical trial is conducted

China, 

References & Publications (2)

Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. — View Citation

Pérez-Simon JA, López-Villar O, Andreu EJ, Rifón J, Muntion S, Diez Campelo M, Sánchez-Guijo FM, Martinez C, Valcarcel D, Cañizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011 Jul;96(7):1072-6. doi: 10.3324/haematol.2010.038356. Epub 2011 Mar 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The efficacy of treatment for steroid-resistant aGVHD	The responses to aGVHD are according to the literature criteria, including completely response (CR), partial response (PR) and no response (NR), and CR is defined as resolution of all symptoms of aGVHD; PR is defined as a decrease by at least 1 GVHD stage in any 1 organ system without deterioration in others 24. Overall response (OR) includes CR and PR.	1 year	No
Secondary	Incidence of infections	Infections are mainly focused on cytomegalovirus (CMV) and Epstein-Barr virus ( EBV) infections during study treatments and within one year after study treatments.	1 year	No
Secondary	Incidence of primary underlying disease relapse		1 year	No
Secondary	Incidence of chronic GVHD		1 year	No