Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.
- Conditions
- Myelofibrosis With High Molecular Risk Mutations
- Interventions
- Registration Number
- NCT02598297
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
- 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
- Patients with prior treatment with ruxolitinib or other JAK inhibitors.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ruxolitinib Ruxolitinib Two tablets of ruxolitinib 5 mg were administered orally twice per day. Ruxolitinib Placebo Ruxolitinib Placebo Two tablets of 5mg placebo were administered orally twice per day.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS-1) From randomization till disease progression (estimated to be assessed up 48 months) 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
- Secondary Outcome Measures
Name Time Method Time to Primary Progression (TTP) From randomization till progression (estimated to be assessed up to 48 months) TTP is defined as time from randomization until disease progression as defined for PFS-1 excluding death as an event.
Overall Survival Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months). To evaluate the effect of ruxolitinib on overall survival
Percentage Change in Spleen Volume From Baseline From baseline and assessed on 12 week intervals until end of treatment (EOT) Change in spleen volume (by MRI/CT) from baseline
Percentage Change in Symptoms From Baseline Using MF-7 From Baseline and assessed every 4 weeks until end of treatment 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.
Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D From Baseline and assessed every 4 weeks until end of treatment 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.Plasma Ruxolitinib Concentrations Week 12, Wk 48 Characterize pharmacokinetics (PK)by utilizing a population PK approach.
Progression Free Survival (PFS-2) From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months) 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
Quality-adjusted Life Years From Baseline 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 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 to First Progressive Splenomegaly (TTPS) From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months) Time to first progressive splenomegaly as determined by spleen volume (by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT).
Time to First Symptomatic Progression (TTSP) From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months) Time to first symptomatic progression as determined by Myelofibrosis 7 Item Symptom Scale (MF-7)
Trial Locations
- Locations (1)
Novartis Investigative Site
🇬🇧Manchester, United Kingdom