Mesenchymal Stem Cell Therapy for the Treatment of Severe or Refractory Inflammatory and/or Autoimmune Disorders
Biological: Mesenchymal Stem Cells (MSC)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Mesenchymal Stem Cell Therapy for the Treatment of Severe or Refractory Inflammatory and/or Autoimmune Disorders|
- Clinical Response Rate [ Time Frame: at week 8 ] [ Designated as safety issue: No ]To assess clinical response rate defined by a 100 points decrease in Crohn's Disease Activity Index.
- Clinical Response [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
- Remission [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]Remission, defined by Crohn's Disease Activity Index <150
- Crohn's Disease Activity Index Level [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
- C-reactive Protein levels [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]C-reactive Protein measured in blood.
- Fecal calprotectin levels [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]Fecal calprotectin measured in stool samples
- Immune modulation investigation [ Time Frame: at week 12. ] [ Designated as safety issue: No ]
The following parameters will be taken in account.
- Nucleated cell count and differential on an automated cell counter;
FACS analysis with determination of the % cells (on total WBC) with the markers :
- CD3+, CD4+, CD8+, CD19+, CD45RA+, CD45RO+, CD56+
- CD3+CD4+, CD3+CD8+; CD3+CD56+;
- CD4+CD45RA+, CD4+CD45RO+;
- Regulatory T-cell (Treg) levels;
- Immunoglobulin levels (baseline and week 12);
- Vβ repertoire of T lymphocytes (baseline and week 12);
- TRECs quantification in T lymphocytes (baseline and week 12).
- Incidence of infections [ Time Frame: by week 12 ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Patients with Crohn's disease (refractory or intolerant to conventional therapies) treated with 2 successive injections of 1.5-2.0 x 10E6 allogenic MSC/kg BW at baseline and 4 weeks later.
Biological: Mesenchymal Stem Cells (MSC)
MSC (1.5-2 cells/kg BW) IV injection, twice at 4 weeks apart
- Collection and expansion of MSC Bone marrow collection and MSC expansion cultures will be carried out at the Laboratory of Cell and Gene Therapy (LTCG) at the University of Liège. Bone marrow (50 ml) will be collected from unrelated donors under local anesthesia, mononuclear cells will be isolated, and cultured for a total of about 4 weeks. After a sufficient number of passages, the cells will be harvested, washed and frozen.
- MSC injections MSC will be thawed and diluted at the Laboratory of Cell and Gene Therapy (LTCG), transported to the hospital ward and injected intravenously within 1 hour of thawing through a central catheter (when available) or a good peripheral vein. A dose of 1.5 - 2.0 x 106/kg recipient MSC should be ideally administered at each infusion. MSC will be infused even if the number of post-thaw cells is lower than that. Patients with Crohn's disease will receive two injections of allogenic MSC 4 weeks apart (week 0 and 4).
- Patients Follow up
3.1. Quality controls of MSC products Quality controls of MSC product will include microscopy, nucleated cell count and differential, cell viability testing, microbiology testing (including standard virology, bacterial culture and detection of mycoplasmal enzymes by bioluminescence, endotoxin testing, karyotype and FACS analysis (cells must be positive for :CD90 > 70%,CD105 > 70 %,CD73 > 70 %; and negative for :CD14 < 5%,CD34 < 5%, CD45 < 5%, CD3 < 1%).
3.2. Toxicities of cell infusions: Potential toxicities associated with MSC infusions will be carefully monitored per the institution's standards and documented on the infusion report and/or the SAE report form. No dosage modifications are scheduled. In case of severe reaction to the first MSC infusion, the second infusion will not be performed.
3.3. Clinical data The following parameters will be followed at baseline as well as at week 2, 4, 8 and 12 : CDAI level, CRP levels, fecal calprotectin levels. In addition, duration of hospitalization, infections, any other serious complication, and eath and survival will be recorded.
3.4. Immunologic data: Immune function in the patient will be monitored at baseline and appropriate intervals: nucleated cell count and differential; FACS analysis with determination of the % cells (on total WBC) with the markers :CD3+, CD4+, CD8+, CD19+, CD45RA+, CD45RO+, CD56+, CD3+CD4+, CD3+CD8+; CD3+CD56+; CD4+CD45RA+, CD4+CD45RO+; CD3-CD56+; regulatory T-cell (Treg) levels; immunoglobulin levels, Vβ repertoire of T lymphocytes; TRECs quantification in T lymphocytes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01540292
|Contact: Yves Beguin, MD, PhDfirstname.lastname@example.org|
|Contact: Edouard Louis, MD, PhDemail@example.com|
|University Hospital Liège||Recruiting|
|Liège, Belgium, 4000|
|Study Chair:||Yves Beguin, MD, PhD||CHU-ULg|
|Principal Investigator:||Edouard Louis, MD, PhD||CHU-ULg|