Proteasome Inhibition in Acute Promyelocytic Leukemia
Status:
Unknown status
Trial end date:
2018-05-01
Target enrollment:
Participant gender:
Summary
The clinical outcome of relapsed acute promyelocytic leukemia (APL) is poor with current
standard of care approaches. Additionally, standard of care warrants an autologous stem cell
transplant to be done once molecular remission is achieved. Unfortunately, the majority of
our patients cannot afford this procedure. We have previously reported the clinical outcome
of relapsed patients who were managed without a stem cell transplants and showed that the
event free survival at 5 years is less than 35%. Pre-clinical data reported from our
laboratory demonstrates that there is significant synergy between arsenic trioxide (ATO;
which is the accepted standard of care agent for relapsed APL) and Bortezomib (a proteasome
inhibitor). We have evaluated this combination extensively in-vitro and this data was
accepted as an oral presentation at the American Society of Hematology (ASH) meeting in 2011.
More recently we have also reported the potential mechanism for this synergy (Poster at ASH
2012). We also have mouse model data which supports these findings. We plan to move this
combination of ATO based therapy combined with Bortezomib to a Phase II clinical trial to
validate these observations. The anticipated potential is that we will have a combination
therapy that is less expensive, cost effective and safe with comparable clinical outcomes to
those treated with the more expensive standard of care which includes an autologous stem cell
transplant and which the majority of our patients cannot afford.