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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 Provincial People's Hospital.
Recruitment status was:  Enrolling by invitation
First Posted : September 7, 2009
Last Update Posted : August 26, 2014
Sponsor:
Collaborator:
Sun Yat-sen University
Information provided by (Responsible Party):
Guangdong Provincial People's Hospital

Tracking Information
First Submitted Date  ICMJE September 4, 2009
First Posted Date  ICMJE September 7, 2009
Last Update Posted Date August 26, 2014
Study Start Date  ICMJE September 2009
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2009)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Allogenic Mesenchymal Stem Cells to Treat Extensive Chronic Graft Versus Host Disease
Official Title  ICMJE 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
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Graft Versus Host Disease
Intervention  ICMJE
  • 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).

    Other Names:
    • Medrol
    • Sandimmun Neoral
    • FK506,prograf
    • Cellcept
    • MTX
  • 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.)

    Other Names:
    • Medral
    • Sandimmun Neoral
    • FK506,Prograf
    • Cellcept,MMF
    • MTX
Study Arms  ICMJE
  • 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.)

    Intervention: Drug: Prednisone and cyclosporine or primary therapies
  • 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.)

    Intervention: Biological: Mesenchymal stem cell (MSC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 4, 2009)
52
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Invasive fungal disease.
  • Active cytomegalovirus (CMV)/Epstein-Barr virus(EBV)/varicella disease).
  • Patient is with a history of hypersensitivity to bovine products.
  • Relapsed malignancy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00972660
Other Study ID Numbers  ICMJE GDREC.[2009]008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guangdong Provincial People's Hospital
Study Sponsor  ICMJE Guangdong Provincial People's Hospital
Collaborators  ICMJE Sun Yat-sen University
Investigators  ICMJE
Principal Investigator: Xin Du, MD.PhD. Guangdong Provincial People's Hospital
PRS Account Guangdong Provincial People's Hospital
Verification Date May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP