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

Nanfang Hospital, Southern Medical University

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Acute Graft-versus-host Disease

Treatments: Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors; Biological: MSCs

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02241018

NFH-MSC-aGVHD-2014

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 14 to 65 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Mesenchymal stem cells

Experimental group

Description:

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.

Treatment:

Biological: MSCs

Drug: CD25 monoclonal antibody

Drug: calcineurin inhibitors

CD25 Mc Ab & calcineurin inhibitors

Experimental group

Description:

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.

Treatment:

Drug: CD25 monoclonal antibody

Drug: calcineurin inhibitors