Dose Finding Study of Post-BMT Decitabine Maintenance Treatment in Higher-risk MDS and MDS/AML
Status:
Unknown status
Trial end date:
2015-12-01
Target enrollment:
Participant gender:
Summary
Brief Scientific Rationale:
Decitabine has been shown to be effective for treatment of MDS and associated with very
limited extramedullary toxicity at the lower doses. Furthermore, the hypomethylating effects
of decitabine require an extended period of therapy and are likely to be more beneficial in
the setting of a minimal residual disease after transplantation. The drug might exert a
cytoreductive effect on the MDS clone, but ex vivo expansion strategy using decitabine and
HDAC inhibitor provides a potential to expand the number of hematopoietic stem cells. There
are lots of evidence which showed the the drug have immunostimulatory effects and can be used
to enhance graft-versus leukemia effects. And also, some investigator suggested that
decitabine could induce FOXP3 expression, promoting the conversion of naïve T cells to Tregs
which are known to suppress GVHD while maintaining GVL effect in allo-SCT setting. As such,
decitabine is an ideal agent to be investigated in the post-transplant setting.
The investigators hypothesized that post-transplant maintenance therapy with decitabine may
reduce relapse rate, which may maximize the beneficial effects from reduced TRM of
ATG-containing FB4 or FB2 conditioning regimen in higher-risk MDS or AML evolving from MDS
patients.