Sympathicomimetic Agonist in Patients With Myeloproliferative Neoplasms With JAK2-mutation
Status:
Completed
Trial end date:
2016-12-01
Target enrollment:
Participant gender:
Summary
The aim of this phase II study is to test a novel concept in the treatment of patients with
myeloproliferative neoplasms (MPN), a disease of the bone marrow. With no current cure
available, MPN are a group of chronic leukemias (blood cancers) in which patients produce too
many blood cells. These increased blood cell numbers cause problems to the patient such as
bleedings or thrombosis and some patients may progress to acute leukemia, a life threatening
condition. Most MPN patients have a gene mutation called JAK2-V617F. The disease is
maintained by mutant MPN stem cells that reside in the bone marrow in specialized locations
called "niches". These niches need connections to the nervous system. New findings show that
these connections are destroyed by the presence of the mutated MPN stem cells. Research teams
found that some drugs (beta3-sympathicomimetics) can restore these damaged niches and at the
same time reduce the MPN disease manifestation in a mouse model of MPN. Such
sympathicomimetic drugs are already being used to treat patients with asthma or hyperactive
bladder. These drugs have shown to have only few side effects. The study tests the effects of
the beta-3-sympathicomimetic drug Mirabegron (Betmiga®) on MPN disease in 39 patients that
carry a JAK2-V617F mutation. The hypothesis is that Mirabegron will have a beneficial effect
on bone marrow niche cells and will thereby improve the disease manifestation in MPN
patients. This study should provide a rapid answer whether targeting the nervous system of
the niche cells could be useful for patients with MPN and warrants to be tested in larger and
more long-term studies.