Multicenter Clinical Trial for the Evaluation of Mesenchymal Stem Cells From Adipose Tissue in Patients With Chronic Graft Versus Host Disease. (CMM/EICH/2008)

Multicenter Clinical Trial Phase I/II Randomized, Controlled, for the Evaluation of Safety and Feasibility of Therapy With Two Different Doses of Allogenic Mesenchymal Stem Cells From Adipose Tissue in Patients With Chronic Graft Versus Host Disease.

The main purpose of this trial is to assess the safety and feasibility of treatment with two-dose infusion of allogeneic mesenchymal stem cells from adipose tissue expanded in vitro in patients undergoing haematopoietic stem cell transplantation (HSCT, who have developed chronic and extensive graft versus host disease (GVHD).

Mesenchymal stem cells (MSCs) express low levels of HLA class I molecules, and do not express class II molecules neither CD40, CD80 and CD86, being unable to induce proliferation of allogeneic lymphocytes. In addition, MSCs inhibit lymphocyte proliferation by inhibiting cell division and maintaining these cells in a quiescent state. This supports the hypothesis that MSCs are universal suppressors.

Study Overview

• Status: Completed
• Conditions: Immune System Diseases; Graft Versus Host Disease; Chronic and Expanded Graft Versus Host Disease
• Intervention / Treatment: Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.; Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Granada., Spain, 18014.
    • Hospital Universitario Virgen de Las Nieves
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio de Sevilla
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
  • Cádiz.
    • Jerez de la Frontera, Cádiz., Spain, 11407
      • Hospital de Jerez de la Frontera.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients who develop chronic extensive GVHD as determined by the National Institute of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD (Biol Blood Marrow Transplant 2005; 11: 945-955), and which meet the following criteria:

1. They have never received therapy for chronic GVHD.
2. They have de novo or quiescent chronic extended GVHD.

Exclusion Criteria:

1. Concomitant severe systemic infection.
2. Oncologic or hematological condition relapse.
3. Pregnancy.
4. Estimated life expectancy less than 1 week.
5. Patients who do not give their informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional treatment plus high dose: 3x10e6 cells / Kg.; Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.	Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.; Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. Low dose: 1 x10e6 / Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.; Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.; Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. High dose: 3 x10e6/Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.
Experimental: Conventional treatment plus low dose: 1x10e6 cells / Kg; Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.	Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.; Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. Low dose: 1 x10e6 / Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.; Other: Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue.; Conventional treatment plus intravenous infusion of allogenic mesenchymal stem cells from adipose tissue. High dose: 3 x10e6/Kg. Conventional treatment:Gradually descending dosage of prednisone and cyclosporin or tacrolimus for at least 46 weeks. Starting dose: 1 mg/Kg/24 h prednisone and 3 mg/Kg/12 h cyclosporin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients in each group that may potentially reduce corticosteroids at week 7, 20 and 42, started immunosuppressive treatment and percentage of patients at week 56 have been suspended on full immunosuppressive treatment	12 months
Overall survival and disease-free survival.	12 months
Changes in lymphocyte subsets and levels of inflammatory and antiinflammatory cytokines in each of the groups.	12 months

Collaborators and Investigators

• Sponsor: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Collaborators: Iniciativa Andaluza en Terapias Avanzadas
• Investigators: Study Chair: Manuel Jurado Chacón, MD, Haematology Department, Hospital Universitario Virgen de las Nieves de Granada. Spain.; Principal Investigator: Ildefonso Espigado, MD, Haematology Department, Hospital Universitario Virgen del Rocío de Sevilla, Spain.; Principal Investigator: Carlos Solano Vercet, MD, Haematology and Oncology Department. Hospital Clínico Universitario de Valencia, Spain.; Principal Investigator: Sebastián Garzón López., MD, Hospital de Jerez de la Frontera, Cádiz. Spain.

Publications and helpful links

Helpful Links

• Andalusian Initiative for Advanced Therapies

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: October 14, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Immune System Diseases; Mesenchymal stem cell; Mesenchymal Stem Cells; Graft versus host disease; Allogeneic mesenchymal stem cell; Adipose tissue; Allotransplant; Allogenic; Chronic; Expanded
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: EudraCT: 2008-004014-27

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No