The researchers are doing this study to find out whether the combination of ruxolitinib and ulixertinib is a safe and effective treatment for people with myelofibrosis. The researchers will test different doses of ulixertinib to find the highest dose that causes few or mild side effects in participants when given in combination with ruxolitinib.
Patients with a diagnosis of primary myelofibrosis, post-ET myelofibrosis, post-PV myelofibrosis, or post-pre-fibrotic myelofibrosis by WHO 2016 criteria.
Age ≥18 years.
Receiving ruxolitinib monotherapy for at least 3 months with stable dose (10 mg BID to 20mg BID) for at least 4 weeks before first dose of study drug. Note: stable ruxolitinib dosing should be achieved according to strict adherence to dose modification/reduction guidelines detailed in the ruxolitinib package insert, for patients with renal impairment, and/or hepatic impairment.
Must have DIPSS+ intermediate 2 or greater risk disease, or MIPSS70+ intermediate or greater risk disease
Use of experimental drug therapy for MF or any other standard drug with the exception of hydroxyurea or ruxolitinib within 2 weeks of starting combination therapy and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better. Hydroxyurea may be utilized to control leukocytosis for up to 4 weeks during study
Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
Unwilling to receive red blood cell transfusion to treat low hemoglobin.
Participants who are receiving any other investigational agents.
Single group
Ulixertinib
DrugThere are 3 planned dose levels of ulixertinib(450 mg BID, 300 mg BID, or 150 mg BID)
Ruxolitinib
DrugRuxolitinib for 28 day cycles.
Dose Limiting Toxicity evaluable participants
If none of the initial 3 patients in a cohort experience a dose limiting toxicity (DLT), then the next dose level will be studied in another cohort of 3 patients. If 1 of the initial 3 patients at a given dose level experience a DLT, up to 3 additional patients will be treated at that same dose level. Escalation will continue if not more than 1 of the 6 patients experience a DLT.
Response to therapy
as defined by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT working criteria)
Click on the lead sponsor to view all of their trials.
Memorial Sloan Kettering Cancer Center
Lead sponsor
BioMed Valley Discoveries, Inc
Collaborator
Incyte Corporation
Collaborator
