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Trial record 1 of 1 for:    CINC424A2353
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Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.

This study has been terminated.
(Unresolvable inability to recruit the patients.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02598297
First received: October 27, 2015
Last updated: May 26, 2017
Last verified: May 2017
  Purpose
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 aims to evaluate ruxolitinib in this patient population.

Condition Intervention Phase
Early Myelofibrosis With High Molecular Risk Mutations Drug: Ruxolitinib Drug: Ruxolitinib Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-controlled, Multicenter, Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Progression free survival (PFS-1) [ Time Frame: From date of randomization until the earliest time for one of the following events in treatment period 1 (estimated to be assessed up 48 months) ]

    Progression free survival (PFS-1) in Treatment Period 1: Disease progression criteria:

    • 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:
  • Time to primary progression (TTP) [ Time Frame: From date of randomization until confirmation of disease progression (estimated to be assessed up to 48 months) ]
    Time to primary progression until disease progression as defined as PFS-1 (excluding death)

  • Time to first progressive splenomegaly (TTPS) [ Time Frame: From randomization until earliest time to progressive splenomegaly (estimated to be assesed 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) [ Time Frame: From randomization until symptomatic progression (MF-7)(estimated to be assesed up to 48 months) ]
    Time to first symptomatic progression as determined by Myelofibrosis 7 Item Symptom Scale (MF-7)

  • Overall survival [ Time Frame: From randomization to date of death due to any cause, if patient is not know to die, censored at last date patient known to be alive (estimated to be assessed up to 48 months). ]
    To evaluate the effect of ruxolitinib on overall survival

  • Plasma ruxolitinib concentrations [ Time Frame: Week 12, Wk 24 (Treatment Period 1) ]
    Compare characteristics of HMR positive early MF patients with patients from previous MF studies (population analysis)

  • Progression free survival (PFS-2) [ Time Frame: From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months) ]

    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 [ Time Frame: Change from Baseline compared with schduled 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.


  • Change in spleen volume from baseline [ Time Frame: Change from Screening compared with schduled study visits at 12 week intervals until End of Treatment ]
    by MRI/CT

  • Changes in symptoms from baseline [ Time Frame: Change from Screening, Baseline compared with schduled study visits at the following intervals, every 4 weeks up to Week 24, every 8 weeks up to Week 48, and every 12 weeks post Wk 48 until End of Treatment and 30 day follow up visit ]
    MF-7

  • change in symptoms from baseline [ Time Frame: Change from Screening, Baseline compared with schduled study visits at the following intervals, every 4 weeks up to Week 24, every 8 weeks up to Week 48, and every 12 weeks post Wk 48 until End of Treatment and 30 day follow up visit ]
    Changes in symptoms using EuroQol-5D-5L (EQ-5D)


Enrollment: 53
Actual Study Start Date: February 3, 2016
Estimated Study Completion Date: March 24, 2021
Estimated Primary Completion Date: October 15, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ruxolitinib
Ruxolitinib 10 mg BID (Blinded)
Drug: Ruxolitinib
Tablet for oral use
Other Name: INC424
Placebo Comparator: Ruxolitinib Placebo
Placebo 10 mg BID (Blinded)
Drug: Ruxolitinib Placebo
Matching placebo tablet for oral use

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Exclusion Criteria:

● Patients with prior treatment with ruxolitinib or other JAK inhibitors.

Other protocol-defined inclusion/exclusion may apply. -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02598297

  Show 93 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02598297     History of Changes
Other Study ID Numbers: CINC424A2353
2014-004928-21 ( EudraCT Number )
Study First Received: October 27, 2015
Last Updated: May 26, 2017
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Ruxolitinib
INC424
early myelofibrosis
High molecular risk mutations
HMR

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on June 23, 2017