Safety and Efficacy Study of Allogenic Mesenchymal Stem Cells to Treat Extensive Chronic Graft Versus Host Disease
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|ClinicalTrials.gov Identifier: NCT00972660|
Recruitment Status : Unknown
Verified May 2010 by Guangdong General Hospital.
Recruitment status was: Enrolling by invitation
First Posted : September 7, 2009
Last Update Posted : August 26, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease||Biological: Mesenchymal stem cell (MSC) Drug: Prednisone and cyclosporine or primary therapies||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||September 2009|
|Estimated Primary Completion Date :||December 2015|
|Estimated Study Completion Date :||December 2017|
Active Comparator: Control group
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.)
Drug: Prednisone and cyclosporine or primary therapies
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.)
Experimental: 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.)
Biological: Mesenchymal stem cell (MSC)
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).
- 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 ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00972660
|Guangdong General Hospital|
|Guangzhou, Guangdong, China, 510080|
|Principal Investigator:||Xin Du, MD.PhD.||Guangdong General Hospital|