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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Sun Yat-sen University
Information provided by (Responsible Party):
Guangdong General Hospital
ClinicalTrials.gov Identifier:
NCT00972660
First received: September 4, 2009
Last updated: August 25, 2014
Last verified: May 2010
  Purpose

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 Intervention Phase
Graft Versus Host Disease
Biological: Mesenchymal stem cell (MSC)
Drug: Prednisone and cyclosporine or primary therapies
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Guangdong General Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Randomization until death or two years post last subject last treatment visit (or clinical cutoff) ] [ Designated as safety issue: No ]
  • Events Free Survival [ Time Frame: Randomization until death or two years post last subject last treatment visit (or clinical cutoff) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Serum cytokine levels and lymphocyte subsets in patients with chronic GVHD [ Time Frame: Achieve best response within the first 3 months after randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: September 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Medral
  • Sandimmun Neoral
  • FK506,Prograf
  • Cellcept,MMF
  • MTX
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:
  • Medrol
  • Sandimmun Neoral
  • FK506,prograf
  • Cellcept
  • MTX

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00972660

Locations
China, Guangdong
Guangdong General Hospital
Guangzhou, Guangdong, China, 510080
Sponsors and Collaborators
Guangdong General Hospital
Sun Yat-sen University
Investigators
Principal Investigator: Xin Du, MD.PhD. Guangdong General Hospital
  More Information

No publications provided

Responsible Party: Guangdong General Hospital
ClinicalTrials.gov Identifier: NCT00972660     History of Changes
Other Study ID Numbers: GDREC.[2009]008
Study First Received: September 4, 2009
Last Updated: August 25, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Guangdong General Hospital:
Mesenchymal stem cell
Efficacy
Safety

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Cyclosporine
Cyclosporins
Methotrexate
Mycophenolate mofetil
Mycophenolic Acid
Prednisone
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2014