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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Graft-versus-host Disease
• Intervention / Treatment: Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors; Biological: MSCs

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 Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mesenchymal stem cells; 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.	Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors; Biological: MSCs
EXPERIMENTAL: CD25 Mc Ab & 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.	Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Incidence of primary underlying disease relapse		1 year
Incidence of chronic GVHD		1 year

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Peking University People's Hospital; Sun Yat-sen University; Guangzhou First People's Hospital; Huazhong University of Science and Technology; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Guangdong Provincial People's Hospital; Third Affiliated Hospital, Sun Yat-Sen University; Guangzhou General Hospital of Guangzhou Military Command; Southern Medical University, China; Academy Military Medical Science, China

Publications and helpful links

General Publications

• Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.
• Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Diez Campelo M, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo 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.
• Zhao K, Lin R, Fan Z, Chen X, Wang Y, Huang F, Xu N, Zhang X, Zhang X, Xuan L, Wang S, Lin D, Deng L, Nie D, Weng J, Li Y, Zhang X, Li Y, Xiang AP, Liu Q. Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial. J Hematol Oncol. 2022 Mar 7;15(1):22. doi: 10.1186/s13045-022-01240-4.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (ANTICIPATED): September 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: September 13, 2014
• First Submitted That Met QC Criteria: September 13, 2014
• First Posted (ESTIMATE): September 16, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): September 16, 2014
• Last Update Submitted That Met QC Criteria: September 13, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; Hematopoietic Stem Cell Transplantation; Acute Graft-versus-host disease; CD25 Monoclonal Antibody
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Antibodies; Antibodies, Monoclonal; Calcineurin Inhibitors
• Other Study ID Numbers: NFH-MSC-aGVHD-2014