Myelofibrosis
Conditions
Interventions
Part 1 Arm 1: Ruxolitinib + Siremadlin
Dose escalation of siremadlin added to existing stable dose of ruxolitinib
Drug: Ruxolitinib
5 mg tablets for oral use
Other Name: INC424, Jakavi
Drug: Siremadl
Sponsors
Yamauchi Kyosuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subjects have diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-essential thrombocythemia (ET) (PET-MF) or post-polycythemia vera (PV) myelofibrosis (PPV-MF) according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) 2007 criteria - Palpable spleen of at least 5 cm from the left costal margin (LCM) to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (a MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted). - Have been treated with ruxolitinib for at least 24 weeks prior to first dose of study treatment - Are stable (no dose adjustments) on the prescribed ruxolitinib dose (between 5 and 25 mg twice a day (BID)) for >=8 weeks prior to first dose of study treatment
Exclusion criteria
Exclusion criteria: - Not able to understand and to comply with study instructions and requirements. - Received any investigational agent for the treatment of MF (except ruxolitinib) within 30 days of first dose of study treatment or within 5 half-lives of the study treatment, whichever is greater - Peripheral blood blasts count of > 10%. - Received a monoclonal antibody (Ab) or immunoglobulin-based agent within 1 year of screening, or has documented severe hypersensitivity reactions/immunogenicity (IG) to a prior biologic - Splenic irradiation within 6 months prior to the first dose of study drug - Received blood platelet transfusion within 28 days prior to first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicities within the first 2 cycles [ Time Frame: Baseline to the end of Cycle 2 (6 or 8 weeks) ] Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study Response rate at the end of cycle 6 or cycle 8 [ Time Frame: Baseline to the end of Cycle 6 or 8 (24 weeks) ] Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite have to be fulfilled | — |
Countries
Australia, Belgium, Canada, Denmark, Germany, Hungary, Italy, Japan, Netherlands, Russian Federation, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactKyosuke Yamauchi
Novartis Pharma. K.K.
Outcome results
None listed