Primary Myelofibrosis (PMF), Post-Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia-Myelofibrosis (PET-MF) MedDRA version: 14.1 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive name: INCB018424
Con
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All subjects must meet the following inclusion criteria: 1.Subjects 18 years of age or older. 2.Subjects must be diagnosed with PMF, PPV-MF or PET-MF, according to the 2008 World Health Organization criteria, irrespective of JAK2 mutation status. 3.Subjects with myelofibrosis requiring therapy must be classified as high risk (3 or more prognostic factors) OR intermediate risk level 2 (2 or more prognostic factors). The prognostic factors, defined by the International Working Group (Cervantes et al, 2009) are: •Age > 65 yrs •Presence of constitutional symptoms (weight loss, fever, night sweats) •Marked anemia (Hgb 25 x10 E9/L) •Circulating blasts =1% * A hemoglobin value =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Any of the following are cause for exclusion from the study: 1.Subjects with a life expectancy of less than 6 months. 2.Females who are pregnant or are currently breastfeeding. 3.Subjects of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid fathering a child or becoming pregnant. •Females of non-childbearing potential are defined as postmenopausal if they have a history of amenorrhea for 1 year if over age 55, OR have been surgically sterile for at least 3 months •For subjects of childbearing potential, appropriate precautions are those that are at least 99% effective in preventing the occurrence of pregnancy. These methods should be communicated to the subjects and their understanding confirmed. 4.Subjects with inadequate bone marrow reserve as demonstrated by: a.Absolute neutrophil count (ANC) that is = 1000/µL. b.Platelet count that is 2.0x ULN. b.Alanine aminotransferase (ALT) > 2.5x institutional upper limit of normal (ULN). c.Creatinine >2.0 mg/dL. 7.Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy: a.Subjects with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed b.Patients with known active hepatitis A, B, C or who are HIV-positive. 8.Subjects must not currently have the option of stem cell transplantation, either because they are not a candidate, or because a suitable donor is not available. 9.Subjects with history of malignancy in past 5 years except for treated, early-stage squamous or basal cell carcinoma of the skin. 10.Subjects with cardiac disease which in the Investigator’s opinion may jeopardize the safety of the subject or the compliance with the protocol. 11.Subjects with currently uncontrolled or unstable angina. 12. Subjects under ongoing treatment with another investigational medication or having been treated with an investigational medication within 14 days or 6 half-lives (whichever is longer) prior to enrollment. 13.Subjects for whom the dose or dose-regimen of any therapies used to treat MF has been modified at any time from 2 weeks prior to the start of Screening through the beginning of Baseline evaluations. 14.Subjects who have had splenic irradiation within 12 months prior to Screening. 15.Subjects with currently rapid or paroxysmal atrial fibrillation. 16.Subjects undergoing treatment with hematopoietic growth factor receptor agonists (ie, erythropoietin (Epo), granulocyte colony stimulating factor (GCSF), romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or 4 weeks prior to Baseline. 17.Subjects with recent (approximately 6 months) myocardial infarction or acute coronary syndrome. 18.Resting heart rate > 110 beats per minute. 19.Resting systolic blood pressure > 160 mm Hg. 20.Resting diastolic blood pressure > 100 mm Hg. 21.Subjects who are unable to comprehend or are unwilling to sign an informed consent form (ICF). 22.Subjects with active alco
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy, safety and tolerability of INC424 given twice daily compared to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) and post essential thrombocythemia myelofibrosis (PET-MF). ;Secondary Objective: To evaluate the population pharmacokinetics of INC424.;Primary end point(s): Proportion of subjects achieving 35% reduction in spleen volume from Baseline to Week 48 as measured by MRI (or by CT for subjects unable to undergo MRI).;Timepoint(s) of evaluation of this end point: Week 48 | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma Ag
Outcome results
None listed