Clinical trial NCT00749164: Allogeneic Mesenchymal Stem Cell for Graft-Versus-Host Disease Treatment
Official title: Allogeneic Mesenchymal Stem Cell Infusion for Treatment Of Steroid Resistant GVHD
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Graft-Versus-Host Disease
Keywords: Mesenchymal stem cells
Umbilical cord
graft-vs-host disease
Steroid resistant
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2008-09-09
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

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.

Donor inclusion criteria:

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.

Donor exclusion criteria:

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.

Primary outcomes:
measure: GVHD re-staging and/or GVHD mortality ,side effects
timeFrame: within the first 30 days (plus or minus 3 days) after MSC transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
Study officials:
affiliation: Hadassah University Hospital
name: Prof. Igor B Resnick, MD, PhD, DSci
role: PRINCIPAL_INVESTIGATOR
References: