Allogeneic Mesenchymal Stem Cell for Graft-Versus-Host Disease Treatment

NCT ID: NCT00749164

Last Updated: 2009-08-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2012-08-31

Brief Summary

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

Conditions

Graft-Versus-Host Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

MSC transplantation

1-2X10\^6 MSC per kg

Intervention Type: PROCEDURE

Eligibility 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.

1. MSC donor must be HIV, HB-s antigen, anti HBc and anti HCV negative.

2. First choice original HSC donor HLA-identical sibling donor.

3. Second choice mismatched related or unrelated donor (for instance MSC frozen and left over from another patient).

4. Third choice or emergency pre-expanded third party umbilical cord/placenta derived MSC.

Exclusion Criteria

1. Patients with poor performance, not expected to survive 5 days.

2. Patients with a history of hypersensitivity to penicillin and/or gentamycine

3. Poor compliance.

1. Donor more than 65 years of age, or unhealthy.

2. Donor who is positive for HIV, hepatitis Bs antigen, HB-s, anti-HBc and anti HCV negative.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

Hadassah Medical Organization

Principal Investigators

Prof. Igor B Resnick, MD, PhD, DSci

Role: PRINCIPAL_INVESTIGATOR

Hadassah University Hospital

Locations

Hadassah University Hospital

Jerusalem, , Israel

Countries

Israel

Central Contacts

Prof. Igor B. Resnick, MD, PhD, DSci

Role: CONTACT

gashka@hadassah.org.il

972-2-6778353

Dr. Polina Stepensky, MD

Role: CONTACT

polina@hadassah.org.il

972-2-6777408

Other Identifiers

IBR-0137-08-HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id