Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
Condition: Primary Myelofibrosis (PMF); Post Polycythaemia Myelofibrosis (PPV MF); Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
MeSH terms: Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: INC424
Intervention description: Ruxolitinib was provided in 5 mg tablets, packaged in bottles. 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ruxolitinib; INC424; myelofibrosis; PMF; post polycythemia myelofibrosis; PPV MF; post-essential thrombocythemia myelofibrosis; PET-MF; Primary Myelofibrosis; Polycythemia; Thrombocythemia; Essential Thrombocytosis; myeloproliferative Disorders; Bone Marrow Diseases; Haematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Haemorrhagic Disorders

Summary:

      The primary objective of this study is to evaluate the efficacy of INC424 in patients with
      PMF, PPV MF, or PET-MF using a composite measure of either an objective endpoint (> 50%
      reduction in splenomegaly using palpitation at 48 weeks) and/or a subjective endpoint (>50%
      reduction in total symptom score at 48 weeks).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must not be eligible for another ongoing INC424 clinical trial.

          -  Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised
             World Health Organization criteria irrespective of JAK2 mutation status.

          -  Patients with PMF requiring therapy must be classified as high risk (3 prognostic
             factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate
             risk level 1 (1 prognostic factor, no more) with an enlarged spleen. The prognostic
             factors, defined by the International Working Group are:

               1. Age > 65 years;

               2. Presence of constitutional symptoms (weight loss, fever, night sweats); marked
                  anemia (Hgb < 10g/dL)*;

               3. Leukocytosis (history of WBC > 25 x109/L);

               4. Circulating blasts > 1%. • A hemoglobin value < 10 g/dL must be demonstrated
                  during the Screening Visit for patients who are not transfusion dependent.
                  Patients receiving regular transfusions of packed red blood cells will be
                  considered to have hemoglobin < 10 g/dL for the purpose of evaluation of risk
                  factors.

          -  Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen
             measuring 5 cm or greater from the costal margin to the point of greatest splenic
             protrusion.

          -  Patients must have a peripheral blood blast count of < 10%.

          -  Patients with adequate liver function defined as direct bilirubin ≤ 2.0 x ULN and ALT
             ≤ 2.5 x ULN.

          -  Patients with adequate renal function defined as serum creatinine ≤ 2 x ULN.

          -  Patients with an ECOG performance status of 0, 1, or 2 (Appendix 5).

        Exclusion criteria:

          -  Patients eligible for hematopoietic stem cell transplantation (suitable candidate and
             a suitable donor is available).

          -  Patients with history of malignancy in past 3 years except for treated, early-stage
             squamous or basal cell carcinoma in situ.

          -  Patients undergoing treatment with hematopoietic growth factor receptor agonists
             (i.e., erythropoietin [Epo], granulocyte colony stimulating factor (GCSF [Neupogen;
             Neulasta], romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or
             4 weeks prior to Baseline.

          -  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).

          -  Patients with cardiac disease which in the Investigator's opinion may jeopardize the
             safety of the patient or the compliance with the protocol.

          -  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.

          -  Patients with known active hepatitis A, B, C or who are HIV-positive.

          -  Patients with inadequate bone marrow reserve as demonstrated by:

               1. Absolute neutrophil count (ANC) that is ≤ 1000/µL.

               2. Platelet count that is < 100,000/µL without the assistance of growth factors,
                  thrombopoietic factors or platelet transfusions.

          -  Patients with any history of platelet counts < 50,000/µL or ANC < 500/µL except during
             treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for
             any other reason.

          -  Patients with coagulation parameters (PT, PTT, INR) ≥ 1.5.

          -  Patients with known hypersensitivity to INC424 or other JAK1/2 inhibitors, or to their
             excipients.

          -  Patients under ongoing treatment with another investigational medication or having
             been treated with an investigational medication within 30 days of screening.

          -  Patients with any concurrent condition that, in the Investigator's opinion would
             jeopardize the safety of the patient or compliance with the protocol.

        Other protocol-defined inclusion/exclusion criteria may apply.