aGVHDNCT05531266
Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease
A study testing hUC-MSCs and glucocorticoids in people with aGVHD, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial summary
Allogenic haemopoietic stem cell transplantation (allo-HSCT) is the effective treatment for many hematologic malignancies and some non-malignant diseases. In recent years, with the rapid improvement of economy and medical level, the number of cases of hematopoietic stem cell transplantation (HSCT) develops rapidly in… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- aGVHD
- What is being tested?
- hUC-MSCs and glucocorticoids
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2022to 1 Mar 2025
- Phase
- Interventional
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient who has undergone an allogeneic haematopoietic stem cell transplantation (HSCT) and developed acute graft versus host disease (aGVHD)
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
- serum creatinine less than twice the upper limit of normal or creatinine clearance greater 50 ml/min within 28 days.
- Patients had recovered from previous treatments
- Signing written informed consent and agreeing with taking designated umbilical cord blood
Who cannot join
- Patients had severe allergy history
- Patients with unstable angina or whose cardiac function grading III-IV.
- Patients with chronic respiratory disease requiring continuous oxygen supplement
- Patients with active hepatitis B or active hepatitis C or AIDS infection
- Patients with Uncontrolled viral or bacterial infections
- Patients with severe psychiatric or physical illness that would limit compliance with study requirements
Show all 10Show fewer
- Patients who received any other investigational study or treatment within 30 days
- Secondary malignancy
- Allergic to blood products
- Other causes which are not suitable for the trial in investigator's consideration
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300041
Aiming Pang, +86-13820398091, pangaiming@ihcams.ac.cn
Erlie Jiang
About this study
Official title: Clinical Study of Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease
Allogenic haemopoietic stem cell transplantation (allo-HSCT) is the effective treatment for many hematologic malignancies and some non-malignant diseases. In recent years, with the rapid improvement of economy and medical level, the number of cases of hematopoietic stem cell transplantation (HSCT) develops rapidly in China. In 2019, 12,323 cases of HSCT were completed in China, with allo-HSCT accounting for 9600 cases of which.
However, Graft versus host disease (GVHD) is one of the most common and serious complications after Allo-HSCT. The incidence of acute GVHD (aGVHD) is as high as 40%-60% in HLA-matched sibling transplantation, and the incidence is even higher in haplo-hematopoietic stem cell transplantation(haplo-HSCT) and unrelated donor transplantation. By Glucksberg grading standard, the 5-year survival rates of grade III and IV aGVHD are 25% and 5% respectively, indicating severe GVHD directly affects the survival of Allo-HSCT patients.
Read more
The first-line treatment for aGVHD is still glucocorticoid, while the effective rate is only 30%-50%. Moreover, due to immunosuppression and increasing risk of infection, the efficacy of second-line treatments including polyclonal antibodies, monoclonal antibodies, immunosuppressants, immunotoxins, chemotherapy drugs, and light therapy for steroid resistant aGVHD is also poor, with the overall survival rate of 5%-30%.
Mesenchymal stem cells (MSCs) are multipotent cells, which can promote engraftment and hematopoietic reconstruction by secreting a variety of hematopoietic promoting factors, expressing adhesion molecules supporting hematopoietic stem cells, guiding homing of hematopoietic stem cells and providing hematopoietic microenvironment. At the same time, MSCs can modulate immune responses by affecting the proliferation of T cells and the migration of T cells and DC, inducing the expansion of Treg cells, inhibiting the secretion of antibodies by B lymphocytes, and regulating the secretion of soluble factors such as NO and IDO. As a result of these characteristics and the poor immunogenicity, MSCs are a promising alternative treatment for GVHD.
Currently, UK and EU guidelines has recommended MSC as a third-line treatment for grade 2-4 acute GVHD, and the safety and efficacy of umbilical cord derived MSCs in the prevention and treatment of GVHD has also been reported by several transplantation centers in China.However, MSCs have not been used for first-line treatment of aGVHD. Therefore, the investigators designed this study to evaluate the safety and efficacy of UC-derived MSCs as the first line treatment in patients with aGVHD.
Read the detailed description
This prospective, randomized and controlled study is to investigate the efficacy and safety of Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease. Investigators will recruit 182 patients with acute leukemia, with 91 of them entering the hUC-MSCs combined with glucocorticoids group. and receiving hUC-MSCs at a dose of 1×10^6 /kilogram (kg) actual body weight at Screening for twice per week in 1-2 weeks and once a week in 3-4 weeks after being rolled into this study, with the glucocorticoid given at the same time. while the other 91 entering the glucocorticoids group receiving glucocorticoids only. Then primary outcomes including the ORR at day 180 post initiation of therapy, as well the secondary outcomes including cumulative relapse incidence、cumulative incidence of chronic GVHD 、cumulative Incidence of infectious complications and cumulative Incidence of lymphoproliferative disease will be measured during 180 days after the intervention being finished.
- Conditions
- aGVHD
- Being tested
- hUC-MSCs, glucocorticoids
- Keywords
- aGVHD, Umbilical Cord Mesenchymal Stem Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hUC-MSCsOther
Participants will be treated with hUC-MSCs at a dose of 1×10^6 /kilogram (kg) actual body weight at Screening for twice per week in 1-2 weeks and once a week in 3-4 weeks after being rolled into this study. At the same time, patients will be treated with glucocorticoids according to patients' condition.
glucocorticoidsOther
Participants were treated with glucocorticoids only.
| Study group | Role | What they receive |
|---|---|---|
| hUC-MSCs combined with glucocorticoids group. | Experimental | 91 patients will be involved in this group Receives: Other: hUC-MSCs |
| glucocorticoids group | Active comparator | 91 patients will be involved in this group Receives: Other: glucocorticoids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy
ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) according to aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.
Measured: 28 days
Secondary outcomes (4)
Cumulative relapse incidence
Defined as the cumulative incidence of relapse after the day of transplantation.
Measured: 180 days
cumulative incidence of chronic GVHD at one year
chronic graft versus host disease will be diagnosed and graded by National Institute of Health Consensus (NIH Consensus).
Measured: 180 days
Cumulative Incidence of Infectious Complications
Defined as cumulative incidence of viral, fungal and bacterial infections.
Measured: 180 days
Cumulative Incidence of lymphoproliferative disease
Defined as the cumulative incidence of lymphoproliferative disease after the day of transplantation.
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2022
- Study start1 Sep 2022 (estimated)
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for aGVHDStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Erlie Jiang, Principal investigator, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05531266
- Sponsor's protocol ID
- 20220831
- Status last verified
- Aug 2022
- First submitted
- 2 Sep 2022
- Last updated
- 7 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT05531266
- Acronym / sponsor ID
- 20220831
- Conditions
- aGVHD
- Keywords
- aGVHD, Umbilical Cord Mesenchymal Stem Cell
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 182 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 1 Sep 2022 (estimated)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 7 Sep 2022 (actual)
- 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.
Allogenic haemopoietic stem cell transplantation (allo-HSCT) is the effective treatment for many hematologic malignancies and some non-malignant diseases. In recent years, with the rapid improvement of economy and medical level, the number of cases of hematopoietic stem cell transplantation (HSCT) develops rapidly in China. In 2019, 12,323 cases of HSCT were completed in China, with allo-HSCT accounting for 9600 cases of which.
However, Graft versus host disease (GVHD) is one of the most common and serious complications after Allo-HSCT. The incidence of acute GVHD (aGVHD) is as high as 40%-60% in HLA-matched sibling transplantation, and the incidence is even higher in haplo-hematopoietic stem cell transplantation(haplo-HSCT) and unrelated donor transplantation. By Glucksberg grading standard, the 5-year survival rates of grade III and IV aGVHD are 25% and 5% respectively, indicating severe GVHD directly affects the survival of Allo-HSCT patients.
The first-line treatment for aGVHD is still glucocorticoid, while the effective rate is only 30%-50%. Moreover, due to immunosuppression and increasing risk of infection, the efficacy of second-line treatments including polyclonal antibodies, monoclonal antibodies, immunosuppressants, immunotoxins, chemotherapy drugs, and light therapy for steroid resistant aGVHD is also poor, with the overall survival rate of 5%-30%.
Mesenchymal stem cells (MSCs) are multipotent cells, which can promote engraftment and hematopoietic reconstruction by secreting a variety of hematopoietic promoting factors, expressing adhesion molecules supporting hematopoietic stem cells, guiding homing of hematopoietic stem cells and providing hematopoietic microenvironment. At the same time, MSCs can modulate immune responses by affecting the proliferation of T cells and the migration of T cells and DC, inducing the expansion of Treg cells, inhibiting the secretion of antibodies by B lymphocytes, and regulating the secretion of soluble factors such as NO and IDO. As a result of these characteristics and the poor immunogenicity, MSCs are a promising alternative treatment for GVHD.
Currently, UK and EU guidelines has recommended MSC as a third-line treatment for grade 2-4 acute GVHD, and the safety and efficacy of umbilical cord derived MSCs in the prevention and treatment of GVHD has also been reported by several transplantation centers in China.However, MSCs have not been used for first-line treatment of aGVHD. Therefore, the investigators designed this study to evaluate the safety and efficacy of UC-derived MSCs as the first line treatment in patients with aGVHD.
Detailed description
This prospective, randomized and controlled study is to investigate the efficacy and safety of Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease. Investigators will recruit 182 patients with acute leukemia, with 91 of them entering the hUC-MSCs combined with glucocorticoids group. and receiving hUC-MSCs at a dose of 1×10^6 /kilogram (kg) actual body weight at Screening for twice per week in 1-2 weeks and once a week in 3-4 weeks after being rolled into this study, with the glucocorticoid given at the same time. while the other 91 entering the glucocorticoids group receiving glucocorticoids only. Then primary outcomes including the ORR at day 180 post initiation of therapy, as well the secondary outcomes including cumulative relapse incidence、cumulative incidence of chronic GVHD 、cumulative Incidence of infectious complications and cumulative Incidence of lymphoproliferative disease will be measured during 180 days after the intervention being finished.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hUC-MSCs combined with glucocorticoids group. | Experimental | Other: hUC-MSCs91 patients will be involved in this group |
| glucocorticoids group | Active comparator | Other: glucocorticoids91 patients will be involved in this group |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patient who has undergone an allogeneic haematopoietic stem cell transplantation (HSCT) and developed acute graft versus host disease (aGVHD)
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
- serum creatinine less than twice the upper limit of normal or creatinine clearance greater 50 ml/min within 28 days.
- Patients had recovered from previous treatments
- Signing written informed consent and agreeing with taking designated umbilical cord blood
Key exclusion criteria (10 listed)
- Patients had severe allergy history
- Patients with unstable angina or whose cardiac function grading III-IV.
- Patients with chronic respiratory disease requiring continuous oxygen supplement
- Patients with active hepatitis B or active hepatitis C or AIDS infection
- Patients with Uncontrolled viral or bacterial infections
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 |
|---|---|---|
| hUC-MSCsParticipants will be treated with hUC-MSCs at a dose of 1×10^6 /kilogram (kg) actual body weight at Screening for twice per week in 1-2 weeks and once a week in 3-4 weeks after being rolled into this study. At the same time, patients will be treated with glucocorticoids according to patients' condition. | Other | hUC-MSCs combined with glucocorticoids group. |
| glucocorticoidsParticipants were treated with glucocorticoids only. | Other | glucocorticoids group |
Primary outcome
Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy
Time frame: 28 days
ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) according to aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.
4 secondary outcomes
Cumulative relapse incidence
Time frame: 180 days
cumulative incidence of chronic GVHD at one year
Time frame: 180 days
Cumulative Incidence of Infectious Complications
Time frame: 180 days
Cumulative Incidence of lymphoproliferative disease
Time frame: 180 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2022.
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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.
Erlie Jiang principal investigator
Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hUC-MSCs and glucocorticoids in people with aGVHD, run by Institute of Hematology & Blood Diseases Hospital, China 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 5 inclusion and 10 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 7 Sep 2022. 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.
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 Aiming Pang (+86-13820398091, pangaiming@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Sep 2022.