Allogeneic Mesenchymal Stem Cell for Graft-Versus-Host Disease Treatment - Full Text View

Sponsor:	Hadassah Medical Organization
Information provided by:	Hadassah Medical Organization
ClinicalTrials.gov Identifier:	NCT00749164

Purpose

Now it is commonly accepted that MSC produce an immune-tolerant environment in different settings. It has been shown (mainly for BM-MSC) that MSC can down-regulate T cells activation. This characteristic of BM derived MSC already has clinical implications and shows their potent effectiveness both in prophylaxis and treatment of resistant GvHD. Ongoing clinical trials of use bone marrow MSC for treatment of steroid resistant GvHD are successfully run on and some bone marrow donor registries included BM-MSC as a material for donation. According to our preclinical studies MSC from cells from marrow, placenta, umbilical cord vessels demonstrate similar pronounced immunosuppressive effect both with autologous and allogeneic lymphocytes. Our preliminary clinical experience shows that BM-MSC is an effective tool for treatment of steroid resistant GVHD. Present study aimed to demonstrate if human UC-MSC has in vivo immunosuppressive effect and can be used for GVHD treatment

Condition	Intervention	Phase
Graft-Versus-Host Disease	Procedure: MSC transplantation	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Allogeneic Mesenchymal Stem Cell Infusion for Treatment Of Steroid Resistant GVHD

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:

GVHD re-staging and/or GVHD mortality ,side effects [ Time Frame: within the first 30 days (plus or minus 3 days) after MSC transplantation ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	September 2009
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Intervention Details:

1-2X10^6 MSC per kg

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

1. Informed consent. 2. Any patient that has undergone allogeneic stem cell transplantation with steroid refractory grades II-IV acute GvHD either occurring post transplant, or induced by donor lymphocyte infusions (DLI) or T-cell add back. A positive biopsy for GvHD is not required if clinical signs and symptoms are characteristic for GvHD and other etiologies are excluded.

3. Patient received best known therapy for GvHD including: i. Patients must receive cyclosporine A (trough level 150-300 ng/ml) or tacrolimus (trough level 5-15 ng/ml).

ii. In addition, steroids must have been given, for instance prednisolone ≥2 mg/kg/day (or equivalent doses of methylprednisolone, etc.) for at least 72h in case of progressive acute GvHD, 5 days non progressive acute GvHD.

iii. Despite this treatment, the patient has unresponsive GvHD after 5 days or progressive acute GvHD after 72 hours. If single organ acute GvHD grade II from gut or liver, either progression from single organ or addition of one or two more organs; e.g., if the patient has grade II acute GvHD of the skin, GvHD is more intense and more widespread, or GvHD also includes liver and/or gut.

iv. Patients with steroid refractory GvHD fulfilling the requirements mentioned in a) - c) may be treated with second line therapy, e.g., MMF, serotherapy, ECP, change of CsA for tacrolimus or vice versa, etc. Failure to respond to additional treatment similar to what is described for steroids in c) is necessary before enrolment in this study.

v. Termination of all GvHD medications other than cyclosporine/tacrolimus/MMF and prednisolone is strongly encouraged.

Exclusion criteria

Patients with poor performance, not expected to survive 5 days.
Patients with a history of hypersensitivity to penicillin and/or gentamycine
Poor compliance.

Donor inclusion criteria:

MSC donor must be HIV, HB-s antigen, anti HBc and anti HCV negative.
First choice original HSC donor HLA-identical sibling donor.
Second choice mismatched related or unrelated donor (for instance MSC frozen and left over from another patient).
Third choice or emergency pre-expanded third party umbilical cord/placenta derived MSC.

Donor exclusion criteria:

Donor more than 65 years of age, or unhealthy.
Donor who is positive for HIV, hepatitis Bs antigen, HB-s, anti-HBc and anti HCV negative.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749164

Contacts

Contact: Prof. Igor B. Resnick, MD, PhD, DSci	972-2-6778353	gashka@hadassah.org.il
Contact: Dr. Polina Stepensky, MD	972-2-6777408	polina@hadassah.org.il

Locations

Israel
Hadassah University Hospital
Jerusalem, Israel, 91120

Sponsors and Collaborators

Hadassah Medical Organization

Investigators

Principal Investigator:

Prof. Igor B Resnick, MD, PhD, DSci

Hadassah University Hospital

More Information

No publications provided

Responsible Party:	Prof. Igor B. Resnick, Hadassah Medical Organization
ClinicalTrials.gov Identifier:	NCT00749164 History of Changes
Other Study ID Numbers:	IBR-0137-08-HMO-CTIL
Study First Received:	July 14, 2008
Last Updated:	August 10, 2009
Health Authority:	Israel: Ministry of Health

Keywords provided by Hadassah Medical Organization:

Mesenchymal stem cells
Umbilical cord
graft-vs-host disease
Steroid resistant

Additional relevant MeSH terms:

Graft vs Host Disease
Immune System Diseases

ClinicalTrials.gov processed this record on February 09, 2012