Myelofibrosis patients with high molecular risk mutations have an intrinsically aggressive disease with increased risk of leukemic transformation and reduced overall survival. As there are no therapies currently established in the subset of high molecular risk patients with early myelofibrosis, the study aimed to evaluate ruxolitinib in this patient population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
49
5 mg tablet for oral use
5 mg placebo tablet for oral use
Progression Free Survival (PFS-1)
Progression free survival (PFS-1) from date of randomization until the occurrence of any of the criteria for disease progression: * Progressive splenomegaly * Circulating peripheral blast counts \> 10% * Leukemic transformation * Hb \< 10g/dl with absolute decrease of at least 3 g/dl from baseline * White blood cell (WBC) counts \> 25 x 103/ μL * MF-7 score ≥ 30 * Death from any cause
Time frame: From randomization till disease progression (estimated to be assessed up 48 months)
Time to Primary Progression (TTP)
TTP is defined as time from randomization until disease progression as defined for PFS-1 excluding death as an event.
Time frame: From randomization till progression (estimated to be assessed up to 48 months)
Percentage Change in Spleen Volume From Baseline
Change in spleen volume (by MRI/CT) from baseline
Time frame: From baseline and assessed on 12 week intervals until end of treatment (EOT)
Percentage Change in Symptoms From Baseline Using MF-7
Percentage change from Baseline in MF-7 total symptom score and 7 individual symptoms at each visit was summarized with descriptive statistics. For this scale, symptoms range from 0 to 10 for the severity experienced within the past 24 hours, with 0 being for absence of symptoms and 10 for worst imaginable symptoms.
Time frame: From Baseline and assessed every 4 weeks until end of treatment
Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D
EQ-ED5 profiles were summarized at baseline and at each scheduled assessment for each of the 5 dimensions separately (Mobility, self-care, usual activities, pain discomfort, anxiety/depression) Only participants with baseline score and at least one non-missing post-baseline score during the treatment period were included. Percentages were based on all these evaluable participants. The 5 scores for mobility, self-care, usual activities, pain/discomfort and anxiety/depression are all self-explanatory (eg "I have no problems walking" to "I am unable to walk"), except for the following overall health check, where 100 is the best of health, and 0 is the worst health.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Novartis Investigative Site
Concord NSW, New South Wales, Australia
Novartis Investigative Site
Liverpool, New South Wales, Australia
Novartis Investigative Site
Wooloongabba, Queensland, Australia
Novartis Investigative Site
Nedlands, Western Australia, Australia
Novartis Investigative Site
Salzburg, Austria
Novartis Investigative Site
Vienna, Austria
Novartis Investigative Site
Antwerp, Belgium
Novartis Investigative Site
Leuven, Belgium
Novartis Investigative Site
Liège, Belgium
Novartis Investigative Site
São Paulo, São Paulo, Brazil
...and 100 more locations
Time frame: From Baseline and assessed every 4 weeks until end of treatment
Overall Survival
To evaluate the effect of ruxolitinib on overall survival
Time frame: Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months).
Plasma Ruxolitinib Concentrations
Characterize pharmacokinetics (PK)by utilizing a population PK approach.
Time frame: Week 12, Wk 48
Progression Free Survival (PFS-2)
PFS-2 assessed by 25% increase over new baseline of PFS-1 in any of the following: ● Progressive splenomegaly ● 25 % increase in MF-7 score with absolute score ≥ 30
Time frame: From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months)
Quality-adjusted Life Years From Baseline
EQ-5D-5L (EuroQol-5D-5L, is a standardized instrument for measuring health outcomes, is consists of a descriptive system and a visual analogue scale - scores can be summarized into a single index score that provides a simple measure of health for clinical and economic appraisal ) The EQ-5D-5L health states will be converted into index values (utilities) from which the QALY (Quality - adjusted life years) will be calculated. QALY will be summarized descriptively by treatment arm.
Time frame: Change from Baseline compared with scheduled study visits at the following intervals every 4 weeks up to week 24, every 8 weeks up to Week 48, every 12 weeks past Wk 48 until End of treatment and 30 day follow up visit
Time to First Progressive Splenomegaly (TTPS)
Time to first progressive splenomegaly as determined by spleen volume (by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT).
Time frame: From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months)
Time to First Symptomatic Progression (TTSP)
Time to first symptomatic progression as determined by Myelofibrosis 7 Item Symptom Scale (MF-7)
Time frame: From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months)