Early Myelofibrosis patients with high molecular risk mutations
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Confirmed diagnosis of MF with bone marrow fibrosis of at least Grade 1; irrespective of JAK2 mutational status Patients with at least one mutation in one of the five HMR genes (ASXL1, EZH2, SRSF2 and IDH1/2) Patients with non-palpable spleen or spleen palpable ? 5 cm from the left costal margin to the point of greatest splenic protrusion Patients with MF-7 score of ? 15, with each individual symptom score of ? 3 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 128 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 192
Exclusion criteria
Exclusion criteria: Patients with prior treatment with ruxolitinib or other JAK inhibitors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate time to disease progression of MF with or without ruxolitinib. To evaluate the changes in spleen volume with or without ruxolitinib. To assess the changes in symptoms using MF-7, EuroQol-5D-5L (EQ-5D). To assess the safety and tolerability of ruxolitinib. To evaluate the effect of ruxolitinib on overall survival. To assess the pharmacokinetics of ruxolitinib. To evaluate the efficacy of ruxolitinib post progression;Primary end point(s): Progression free survival (PFS-1) from date of randomization until the occurrence of any of the criteria for disease progression (See Section 10.4.1 for details on criteria and required confirmation): - Progressive splenomegaly - Circulating peripheral blast counts > 10% - Leukemic transformation - Hb 25 x 103/ ?L - MF-7 score ? 30 - Death from any cause;Timepoint(s) of evaluation of this end point: Primary endpoint evaluated after 90 PFS-1 events are documented.;Main Objective: To evaluate the effect of ruxolitinib in delaying progression of MF from early disease to more advanced disease stages. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to primary progression Time to first progressive splenomegaly as determined by spleen volume (by MRI/CT) Change in spleen volume (by MRI/CT) from baseline Time to first symptomatic progression as determined by MF-7 Quality-adjusted life years using EQ-5D Changes in symptoms using MF-7 and EQ-5D from baseline Monitoring the frequency, duration, and severity of adverse events including abnormalities in vital signs, laboratory parameters and ECG data Overall survival Plasma ruxolitinib concentrations. Characterize PK by utilizing a Population PK approach Progression free survival (PFS-2) assessed by 25% increase over new baseline of PFS-1 in any of the following (See Section 10.5.1 of the protocol for details): - Progressive splenomegaly - 25 % increase in MF-7 score with absolute score ? 30;Timepoint(s) of evaluation of this end point: Secondary endpoint evaluated after 90 PFS-1 events are documented. | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, China, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Norway, Poland, Portugal, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed