Acute Graft-versus-host DiseasePhase 2/3NCT02241018
MSCs Combined With CD25 Monoclonal Antibody and Calcineurin Inhibitors for Treatment of Steroid-resistant aGVHD
A Phase 2/3 study testing CD25 monoclonal antibody, calcineurin inhibitors and MSCs in people with Acute Graft-versus-host Disease, run by Nanfang Hospital, Southern Medical University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Acute Graft-versus-host Disease
- What is being tested?
- CD25 monoclonal antibody, calcineurin inhibitors and MSCs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- Sep 2014to Dec 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- age of 14-65 years
- steroid-resistant aGVHD
- subjects (or their legally acceptable representatives) must have signed an informed consent document
Who cannot join
- 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 locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematology,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Ren Lin, MD, +86-020-62787883, lansinglinren@hotmail.com
Qifa Liu, MD
About this study
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
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.
Read the 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.
- Conditions
- Acute Graft-versus-host Disease
- Being tested
- CD25 monoclonal antibody, calcineurin inhibitors, MSCs
- Keywords
- Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells, CD25 Monoclonal Antibody, Acute Graft-versus-host disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD25 monoclonal antibodyDrug
calcineurin inhibitorsDrug
MSCsBiological
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal stem cells | Experimental | 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. Receives: Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors; Biological: MSCs |
| CD25 Mc Ab & calcineurin inhibitors | Experimental | 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. Receives: Drug: CD25 monoclonal antibody; Drug: calcineurin inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
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.
Measured: 1 year
Incidence of primary underlying disease relapse
Measured: 1 year
Incidence of chronic GVHD
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionSep 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acute Graft-versus-host DiseaseStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Guangdong Provincial People's Hospital, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou First People's Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Southern Medical University, China, Peking University People's Hospital, Huazhong University of Science and Technology, Sun Yat-sen University, Academy Military Medical Science, China
- Responsible party
- Principal investigator, Qifa Liu, Nanfang Hospital, Southern Medical University
- Investigators
- Qifa Liu, MD, Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02241018
- Sponsor's protocol ID
- NFH-MSC-aGVHD-2014
- Status last verified
- Sep 2014
- First submitted
- 13 Sep 2014
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 15121408Perez-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.
PubMed 21393326Zhao K, Lin R, Fan Z, Li Z, Chen X, Xuan L, Huang F, Xu N, Wu X, Chen S, Sun J, Zhang X, Weng J, Li Y, Li Y, Lin D, Nie D, Wang S, Xu X, Zhang X, Li Y, Xiang AP, Wang Y, Liu Q. Reduced morbidity and mortality of cGVHD in patients who received treatment with mesenchymal stromal cells for steroid-resistant aGVHD: long-term follow-up of a randomized phase 3 trial. Exp Hematol Oncol. 2025 Jul 9;14(1):95. doi: 10.1186/s40164-025-00687-8.
PubMed 40635107Zhao 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.
PubMed 35255929
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02241018
- Acronym / sponsor ID
- NFH-MSC-aGVHD-2014
- Conditions
- Acute Graft-versus-host Disease
- Keywords
- Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells, CD25 Monoclonal Antibody, Acute Graft-versus-host disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Collaborators
- Guangdong Provincial People's Hospital, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou First People's Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Southern Medical University, China, Peking University People's Hospital, Huazhong University of Science and Technology, Sun Yat-sen University, Academy Military Medical Science, China
- Study start
- Sep 2014
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 16 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal stem cells | Experimental | Drug: CD25 monoclonal antibody, Drug: calcineurin inhibitors, Biological: MSCsMSCs 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 | Experimental | Drug: CD25 monoclonal antibody, Drug: calcineurin inhibitorsCD25 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. |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- age of 14-65 years
- steroid-resistant aGVHD
- subjects (or their legally acceptable representatives) must have signed an informed consent document
Key exclusion criteria (2 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD25 monoclonal antibody | Drug | CD25 Mc Ab & calcineurin inhibitors, Mesenchymal stem cells |
| calcineurin inhibitors | Drug | CD25 Mc Ab & calcineurin inhibitors, Mesenchymal stem cells |
| MSCs | Biological | Mesenchymal stem cells |
Primary outcome
The efficacy of treatment for steroid-resistant aGVHD
Time frame: 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.
3 secondary outcomes
Incidence of infections
Time frame: 1 year
Incidence of primary underlying disease relapse
Time frame: 1 year
Incidence of chronic GVHD
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2014.
- Background: PubMed 15121408Le 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.
- Background: PubMed 21393326Perez-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.
- Derived from this study: PubMed 40635107Zhao K, Lin R, Fan Z, Li Z, Chen X, Xuan L, Huang F, Xu N, Wu X, Chen S, Sun J, Zhang X, Weng J, Li Y, Li Y, Lin D, Nie D, Wang S, Xu X, Zhang X, Li Y, Xiang AP, Wang Y, Liu Q. Reduced morbidity and mortality of cGVHD in patients who received treatment with mesenchymal stromal cells for steroid-resistant aGVHD: long-term follow-up of a randomized phase 3 trial. Exp Hematol Oncol. 2025 Jul 9;14(1):95. doi: 10.1186/s40164-025-00687-8.
- Derived from this study: PubMed 35255929Zhao 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Qifa Liu, MD principal investigator
Nanfang Hospital, Southern Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing CD25 monoclonal antibody, calcineurin inhibitors and MSCs in people with Acute Graft-versus-host Disease, run by Nanfang Hospital, Southern Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ren Lin (+86-020-62787883, lansinglinren@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The efficacy of treatment for steroid-resistant aGVHD (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02241018, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2014.