Graft-versus-host-disease Clinical Trial
Official title:
Treatment of Steroid Resistant Grade II to IV GVHD by Infusion MSCof Mesenchymal Stem Cells Expanded With Human Plasma and Platelet Lysate a Phase I/II Study
For numerous malignant diseases allogeneic hematopoietic stem cell transplantation (HSCT) is
the only curative therapy. One of the major complications is the occurrence of acute
graft-versus-host-disease (aGVHD). Thirty to eighty percent of patients after HSCT develop
aGVHD despite the prophylactic application of different immunosuppressive drugs.
The response rates to the conventional first line treatment are only 15-35%4. In case of a
steroid refractory aGVHD different therapeutic strategies have been evaluated, but with no
satisfactory results so far. The mortality of patients suffering from steroid refractory
aGVHD remains at 75-80%. Therefore, it remains important to search for new therapeutical
strategies for the treatment of aGVHD.
For numerous malignant and non-malignant hematological diseases allogeneic hemato¬poietic
stem cell transplantation (HSCT) is the only curative therapy. One of the major
complications is the occurrence of acute graft-versus-host-disease (aGVHD). Thirty to eighty
percent of patients after HSCT develop aGVHD despite the prophylactic application of
different immunosuppressive drugs depending on risk factors such as HLA-match, donor
relation, age etc.1-3.
First line therapy of aGVHD > grade I consists of steroids at a dose of 2 mg/kg. The
response rates to this treatment are only 15-35%4. In case of a steroid refractory aGVHD
different therapeutic strategies have been evaluated, but with no satisfactory results so
far. The mortality of patients suffering from steroid refractory aGVHD remains at 75-80%,
although numerous studies with different treatment strategies have been conducted2-5.
Therefore, it remains important to search for new therapeutical strategies for the treatment
of aGVHD.
The first patient to receive mismatched Mesenchymal Stem Cells was a twenty-year-old woman
with acute myeloid leukemia treated with peripheral blood stem cells combined with MSC from
her haploidentical father. Lazarus et al. reported on 46 patients who received HSCs and
culture-expanded MSCs from HLA-identical siblings. Moderate to severe acute GvHD was
observed in 28% of the patients, and chronic GvHD was seen in 61%. The two-year
progression-free survival was observed in 53% of the patients. MSC infusion caused no acute
or long-term MSC-associated adverse events.
Traditionally, for MSC isolation and expansion, fetal calf serum (FCS) supplemented media
are used. The use of FCS has however several drawbacks and potential problems. We have
therefore established a MSC culture protocol in animal serum free conditions using human
platelet lysate and human plasma instead.
The present phase I/II study is designed to gather further insight into the clinical benefit
in 50 patients (adults and children) with GvHD exerted by MSC expanded with human platelet
lysate and plasma
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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