Safety and Efficacy Study of Allogenic Mesenchymal Stem Cells to Treat Extensive Chronic Graft Versus Host Disease

August 25, 2014 updated by: Guangdong Provincial People's Hospital

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Guangdong General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.)

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Within the first 3 months (plus or minus 7 days) after randomization

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: Randomization until death or two years post last subject last treatment visit (or clinical cutoff)
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)
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)
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
Achieve best response within the first 3 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangdong Provincial People's Hospital

Collaborators

Sun Yat-sen University

Investigators

  • Principal Investigator: Xin Du, MD.PhD., Guangdong Provincial People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

September 4, 2009

First Submitted That Met QC Criteria

September 4, 2009

First Posted (Estimate)

September 7, 2009

Study Record Updates

Last Update Posted (Estimate)

August 26, 2014

Last Update Submitted That Met QC Criteria

August 25, 2014

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GDREC.[2009]008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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