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

Phase 2

• Conditions: Acute Graft-versus-host Disease
• Interventions: Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors; Biological: MSCs

• Registration Number: NCT02241018
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief 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.

Detailed 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.

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: 200

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mesenchymal stem cells	MSCs	MSCs will be given at a median dose of 1×10\^6 cells/kg once weekly for 4 dose (as 1 cycle) or until CR. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. Besides, CD25 monoclonal antibody (20mg/kg) will be administered at day 1,4,8,15, 21 and calcineurin inhibitors will also be used.
CD25 Mc Ab & calcineurin inhibitors	CD25 monoclonal antibody	CD25 monoclonal antibody (20mg/kg, day 1,4,8,15,21) will be administered combined with calcineurin inhibitors. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given.
CD25 Mc Ab & calcineurin inhibitors	calcineurin inhibitors	CD25 monoclonal antibody (20mg/kg, day 1,4,8,15,21) will be administered combined with calcineurin inhibitors. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given.
Mesenchymal stem cells	calcineurin inhibitors	MSCs will be given at a median dose of 1×10\^6 cells/kg once weekly for 4 dose (as 1 cycle) or until CR. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. Besides, CD25 monoclonal antibody (20mg/kg) will be administered at day 1,4,8,15, 21 and calcineurin inhibitors will also be used.
Mesenchymal stem cells	CD25 monoclonal antibody	MSCs will be given at a median dose of 1×10\^6 cells/kg once weekly for 4 dose (as 1 cycle) or until CR. The response should be evaluated at 3 and 4 weeks. If symptoms of aGVHD progress at 3 weeks or the patients have NR at 4 weeks, these patients will switch to other therapy. If patients achieved PR at 4 weeks, another cycle will be given. Besides, CD25 monoclonal antibody (20mg/kg) will be administered at day 1,4,8,15, 21 and calcineurin inhibitors will also be used.

Primary Outcome Measures

Name	Time	Method
The efficacy of treatment for steroid-resistant aGVHD	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of infections	1 year	Infections are mainly focused on cytomegalovirus (CMV) and Epstein-Barr virus ( EBV) infections during study treatments and within one year after study treatments.
Incidence of primary underlying disease relapse	1 year
Incidence of chronic GVHD	1 year

Trial Locations

Locations (1)

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