Primary Myelofibrosis (PMF), Post-Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia-Myelofibrosis (PET-MF) MedDRA version: 14.0 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: INCB0118424
Pharmaceutical Form: Tablet
INN or Proposed INN: Proposed INN ruxolitinib
Current Sponsor code: INC3018424
Concentration unit: mg milligram(s)
Conc
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients 18 years of age or older 2. Patients must be diagnosed with PMF, PPV-MF or PET-MF irrespective of JAK2 mutation status, guided by the criteria outlined in the 2008 World Health Organization (WHO) criteria for PMF (Table 2 in Tefferi and Vardiman, 2008, Appendix 1a), and the proposed criteria for PPV-MF and PET-MF outlined by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) (Table 1 in Barosi et al, 2008, Appendix 1b). 3. Patients 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) OR intermediate risk level 1 (1 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 > 10% of the baseline value in the year preceding MF diagnosis, unexplained fever, or excessive night sweats persisting for more than 1 month) • marked anemia (Hgb 25 x109/L) • circulating blasts >= 1% * A hemoglobin value = 75 x 109/L for the first stratum of the trial or PLT counts = 50 x 109/L for the second stratum • coagulation parameters as follows: INR and PTT 0.8 x ULN and D-dimer or fibrinogen degradation products (FDP) within normal limits NOTE: If at the planned day of study treatment initiation the PLT counts are outside the permitted range, for the respective stratum, then an additional PLT count assessment will be conducted in = 1.5 x 109/L at Screening 5. Patients with peripheral blood blast count of =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception (confirmed by a positive hCG laboratory test > 5 mIU/mL) and until the termination of gestation 2. Patients of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid becoming pregnant or fathering a child • Females of non-childbearing potential are defined as women who (a) are >= 55 years of age with history of amenorrhea for 1 year with serum FSH levels > 40 mIU/mL, OR (b) are surgically sterile for at least 12 weeks • For females of childbearing potential, or for males, appropriate precautions (at least two birth control methods) are those that are at least 99% effective in preventing the occurrence of pregnancy. These methods should be communicated to the patients and their understanding confirmed (Appendix III) 3. Patients undergoing treatment with hematopoietic growth factor receptor agonists (i.e. erythropoietin (EPO), granulocyte colony stimulating factor (GCSF), romiplostim, eltrombopag) for at least 30 days prior to receiving the first dose of study drug 4. Patients with any history of PLT counts = 0.5 mg/dL • alanine aminotransferase (ALT) > 2.5 x ULN • MDRD-eGFR < 30 mL/min/1.73m2 or on dialysis (Appendix VI) 9. Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed 10. Patients with known active hepatitis A, B or C at Screening or with known HIV positivity 11. Patients being treated concurrently with a potent systemic inhibitor of CYP3A4 at the time of Screening (ketoconazole, clarithromycin, itraconazole, nefazodone or telithromycin, see Appendix VII) 12. Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) 13. Patients must not currently have the option of stem cell transplantation at the time of the screening assessments, either because they are not a candidate for the procedure, in the investigator’s expert judgment, or because a suitable donor is not available 14. Patients with an active malignancy over the previous 5 years, except treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin, with no evidence for recurrence in the past 3 years 15. Patients with currently rapid or paroxysmal atrial fibrillation, currently uncontrolled or unstable angina, recent (approximately 6 months) myocardia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To establish the Maximum Safe Starting Dose of INC424 in patients with MF and baseline PLT count = 75 x 109/L (first stratum) and PLT count = 50 x 109/L (second stratum);Secondary Objective: • To characterize the safety of INC424 • To characterize the pharmacokinetics of INC424 in this patient population • To characterize the pharmacokinetic-pharmacodynamic relationship of this population • To obtain estimates of efficacy ;Primary end point(s): Incidence rate of Dose Limiting Toxicities (DLT) | — |
Countries
Austria, Netherlands, United Kingdom
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed