Graft Versus Host DiseasePhase 2NCT00972660
Safety and Efficacy Study of Allogenic Mesenchymal Stem Cells to Treat Extensive Chronic Graft Versus Host Disease
A Phase 2 study testing Mesenchymal stem cell (MSC) and Prednisone and cyclosporine or primary therapies in people with Graft Versus Host Disease, run by Guangdong Provincial People's Hospital at 1 site in China.
Trial summary
Study Design: Treatment, Randomized, Open Label, Parallel Assignment,Safety/Efficacy Study. The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSC) expanded ex-vivo infusion for the treatment of patients who have developed a newly diagnosed extensive or refractory chronic graft… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Mesenchymal stem cell (MSC) and Prednisone and cyclosporine or primary therapies
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteChina
- Study dates
- Sep 2009to Dec 2017
- Phase
- Phase 2
- 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
- Informed consent obtained from patient and donor.
- Any patient who has undergone allogeneic stem cell transplantation with extensive chronic GVHD.
- Have not received additional agent for cGVHD within 3 months.
- Expected life is more than 90 days.
- Adequate pulmonary function with no evidence of chronic obstructive or severe restrictive pulmonary disease.
- Adequate cardiac function with no evidence of uncontrolled high blood pressure,congestive heart failure, angina pectoris, acute myocardial infarction within 6 months prior to the process.
Who cannot join
- Invasive fungal disease.
- Active cytomegalovirus (CMV)/Epstein-Barr virus(EBV)/varicella disease).
- Patient is with a history of hypersensitivity to bovine products.
- Relapsed malignancy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Ex-Vivo Cultured Allogenic Mesenchymal Stem Cells For the Treatment of Extensive Chronic Graft Versus Host Disease
Study Design: Treatment, Randomized, Open Label, Parallel Assignment,Safety/Efficacy Study.
The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSC) expanded ex-vivo infusion for the treatment of patients who have developed a newly diagnosed extensive or refractory chronic graft versus host disease (chronic GVHD) to the usual therapeutic measures.
Read the detailed description
Chronic graft-versus-host disease (GVHD) is one of the main limitations to successful allogeneic hematopoietic stem cell transplantation (HSCT), and has a substantial impact not only on survival but also on the quality of life of otherwise cancer-free patients. Half of the patients undergoing a HLA-identical allografts who survive beyond 100 days may require long-term immunosuppressive treatment for extensive chronic GVHD, often for more than 2 years. More than one-third of patients with chronic GVHD do not respond to first-line therapy, which often involves combinations of corticosteroids and a calcineurin inhibitor. There is no standard second-line or salvage therapy for these patients and they have a poor outcome.
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells that can differentiate into various lineages and have been used to repair injured tissues. Recently, MSCs have also shown unique immunomodulatory properties ex-vivo, including inhibition of T-cell proliferation after stimulation by allo-antigens and mitogens, and prevention of the activity of cytotoxic T cells.MSCs have been used for the prophylaxis of acute GVHD and for the treatment of patients with steroid-refractory acute GVHD,but rarely have been used for extensive chronic GVHD.
Development of new therapeutic agents and strategies to rescue patients with extensive chronic GVHD would provide a significant benefit in an area of unmet medical need.
In this study, a single center randomized, non blinded Phase II clinical trial is proposed to study the safety and efficacy of mesenchymal stem cells (MSC) in the management of extensive chronic GVHD newly or refractory to the usual therapeutic measures.
Expanded MSC will be infused at a dose of 2 million cells/kg twice a week for 2 weeks and weekly for the following two weeks (six doses totally)in patients based first-line therapy (steroid plus cyclosporin A ) or their primary immunosuppressive therapies.
- Conditions
- Graft Versus Host Disease
- Being tested
- Mesenchymal stem cell (MSC), Prednisone and cyclosporine or primary therapies
- Keywords
- Mesenchymal stem cell, Efficacy, Safety
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stem cell (MSC)Biological
Also called Medrol, Sandimmun Neoral, FK506,prograf, Cellcept
Experimental:Mesenchymal stem cell(MSC). Patients with newly diagnosed extensive cGVHD: prednisone 1mg/kg + cyclosporine or tacrolimus and MSC 2×1,000,000 MSC/kg, IV twice a week for the first two weeks and weekly for the following two weeks(6 doses totally).
Refractory extensive cGVHD: receive primary treatment (prednisone + cyclosporine or tacrolimus, or plus mycophenolate mofetil, or plus methotrexate ) and MSC2×1,000,000 MSC/kg, IV twice a week for the first two weeks and weekly for the following two weeks(6 doses totally).
Prednisone and cyclosporine or primary therapiesDrug
Also called Medral, Sandimmun Neoral, FK506,Prograf, Cellcept,MMF
Patients with newly diagnosed extensive cGVHD: prednisone 1mg/kg + cyclosporine or tacrolimus
Patients with refractory extensive cGVHD: primary treatment (eg.prednisone 1mg/kg + cyclosporine or tacrolimus,or plus mycophenolate mofetil, or methotrexate.)
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Patients with newly diagnosed extensive cGVHD receive prednisone and cyclosporine or tacrolimus.
Patients with refractory extensive cGVHD receive primary treatment (eg,prednisone and cyclosporine or tacrolimus, or plus mycophenolate mofetil, or methotrexate.) Receives: Drug: Prednisone and cyclosporine or primary therapies |
| Mesenchymal stem cell (MSC) | Experimental | Patients with newly diagnosed extensive cGVHD receive MSC plus prednisone and cyclosporine or tacrolimus.
Patients with refractory extensive cGVHD receive MSC plus their primary immunosuppressive treatment (eg. prednisone + cyclosporine or tacrolimus, or plus mycophenolate mofetil, or plus methotrexate.) Receives: Biological: Mesenchymal stem cell (MSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The total Response rate defined as patients with complete and partial response.
Measured: Within the first 3 months (plus or minus 7 days) after randomization
Secondary outcomes (4)
Overall Survival
Measured: Randomization until death or two years post last subject last treatment visit (or clinical cutoff)
Events Free Survival
Measured: Randomization until death or two years post last subject last treatment visit (or clinical cutoff)
The percentage of patients who can taper or discontinue the immunosuppressive agents
Measured: Randomization untill two years post the last subject last treatment visit (or clinical cutoff)
Serum cytokine levels and lymphocyte subsets in patients with chronic GVHD
Measured: Achieve best response within the first 3 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionDec 2015 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Guangdong Provincial People's HospitalThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Yat-sen University
- Responsible party
- Sponsor
- Investigators
- Xin Du, MD.PhD., Principal investigator, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00972660
- Sponsor's protocol ID
- GDREC.[2009]008
- Status last verified
- May 2010
- First submitted
- 4 Sep 2009
- Last updated
- 26 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Ex-Vivo Cultured Allogenic Mesenchymal Stem Cells For the Treatment of Extensive Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT00972660
- Acronym / sponsor ID
- GDREC.[2009]008
- Conditions
- Graft Versus Host Disease
- Keywords
- Mesenchymal stem cell, Efficacy, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Collaborators
- Sun Yat-sen University
- Study start
- Sep 2009
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 7 Sep 2009 (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.
Study Design: Treatment, Randomized, Open Label, Parallel Assignment,Safety/Efficacy Study.
The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSC) expanded ex-vivo infusion for the treatment of patients who have developed a newly diagnosed extensive or refractory chronic graft versus host disease (chronic GVHD) to the usual therapeutic measures.
Detailed description
Chronic graft-versus-host disease (GVHD) is one of the main limitations to successful allogeneic hematopoietic stem cell transplantation (HSCT), and has a substantial impact not only on survival but also on the quality of life of otherwise cancer-free patients. Half of the patients undergoing a HLA-identical allografts who survive beyond 100 days may require long-term immunosuppressive treatment for extensive chronic GVHD, often for more than 2 years. More than one-third of patients with chronic GVHD do not respond to first-line therapy, which often involves combinations of corticosteroids and a calcineurin inhibitor. There is no standard second-line or salvage therapy for these patients and they have a poor outcome.
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells that can differentiate into various lineages and have been used to repair injured tissues. Recently, MSCs have also shown unique immunomodulatory properties ex-vivo, including inhibition of T-cell proliferation after stimulation by allo-antigens and mitogens, and prevention of the activity of cytotoxic T cells.MSCs have been used for the prophylaxis of acute GVHD and for the treatment of patients with steroid-refractory acute GVHD,but rarely have been used for extensive chronic GVHD.
Development of new therapeutic agents and strategies to rescue patients with extensive chronic GVHD would provide a significant benefit in an area of unmet medical need.
In this study, a single center randomized, non blinded Phase II clinical trial is proposed to study the safety and efficacy of mesenchymal stem cells (MSC) in the management of extensive chronic GVHD newly or refractory to the usual therapeutic measures.
Expanded MSC will be infused at a dose of 2 million cells/kg twice a week for 2 weeks and weekly for the following two weeks (six doses totally)in patients based first-line therapy (steroid plus cyclosporin A ) or their primary immunosuppressive therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: Prednisone and cyclosporine or primary therapiesPatients with newly diagnosed extensive cGVHD receive prednisone and cyclosporine or tacrolimus. Patients with refractory extensive cGVHD receive primary treatment (eg,prednisone and cyclosporine or tacrolimus, or plus mycophenolate mofetil, or methotrexate.) |
| Mesenchymal stem cell (MSC) | Experimental | Biological: Mesenchymal stem cell (MSC)Patients with newly diagnosed extensive cGVHD receive MSC plus prednisone and cyclosporine or tacrolimus. Patients with refractory extensive cGVHD receive MSC plus their primary immunosuppressive treatment (eg. prednisone + cyclosporine or tacrolimus, or plus mycophenolate mofetil, or plus methotrexate.) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Informed consent obtained from patient and donor.
- Any patient who has undergone allogeneic stem cell transplantation with extensive chronic GVHD.
- Have not received additional agent for cGVHD within 3 months.
- Expected life is more than 90 days.
- Adequate pulmonary function with no evidence of chronic obstructive or severe restrictive pulmonary disease.
Key exclusion criteria (4 listed)
- Invasive fungal disease.
- Active cytomegalovirus (CMV)/Epstein-Barr virus(EBV)/varicella disease).
- Patient is with a history of hypersensitivity to bovine products.
- Relapsed malignancy.
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 |
|---|---|---|
| Mesenchymal stem cell (MSC)Also: Medrol, Sandimmun Neoral, FK506,prograf, CellceptExperimental:Mesenchymal stem cell(MSC). Patients with newly diagnosed extensive cGVHD: prednisone 1mg/kg + cyclosporine or tacrolimus and MSC 2×1,000,000 MSC/kg, IV twice a week for the first two weeks and weekly for the following two weeks(6 doses totally). Refractory extensive cGVHD: receive primary treatment (prednisone + cyclosporine or tacrolimus, or plus mycophenolate mofetil, or plus methotrexate ) and MSC2×1,000,000 MSC/kg, IV twice a week for the first two weeks and weekly for the following two weeks(6 doses totally). | Biological | Mesenchymal stem cell (MSC) |
| Prednisone and cyclosporine or primary therapiesAlso: Medral, Sandimmun Neoral, FK506,Prograf, Cellcept,MMFPatients with newly diagnosed extensive cGVHD: prednisone 1mg/kg + cyclosporine or tacrolimus Patients with refractory extensive cGVHD: primary treatment (eg.prednisone 1mg/kg + cyclosporine or tacrolimus,or plus mycophenolate mofetil, or methotrexate.) | Drug | Control group |
Primary outcome
The total Response rate defined as patients with complete and partial response.
Time frame: Within the first 3 months (plus or minus 7 days) after randomization
4 secondary outcomes
Overall Survival
Time frame: Randomization until death or two years post last subject last treatment visit (or clinical cutoff)
Events Free Survival
Time frame: Randomization until death or two years post last subject last treatment visit (or clinical cutoff)
The percentage of patients who can taper or discontinue the immunosuppressive agents
Time frame: Randomization untill two years post the last subject last treatment visit (or clinical cutoff)
Serum cytokine levels and lymphocyte subsets in patients with chronic GVHD
Time frame: Achieve best response within the first 3 months after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2014.
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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.
Xin Du, MD.PhD. principal investigator
Guangdong Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesenchymal stem cell (MSC) and Prednisone and cyclosporine or primary therapies in people with Graft Versus Host Disease, run by Guangdong Provincial People's Hospital 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 6 inclusion and 4 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 26 Aug 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 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The total Response rate defined as patients with complete and partial response. (time frame: Within the first 3 months (plus or minus 7 days) after randomization). 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 26 Aug 2014.