INC424 for Patients With Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.
Condition: Myelofibrosis
MeSH terms: Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: INC424
Intervention description: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2233.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelofibrosis; Primary myelofibrosis; PMF; Post polycythemia myelofibrosis; PPV MF; Post-essential thrombocythemia myelofibrosis; PET-MF; INC424; Ruxolitinib

Summary:

      The primary objective of this study was to collect additional safety of INC424 in patients
      with Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia
      Myelofibrosis, who either received prior treatment with commercially available agents or who
      have never received treatment.
    

Eligibility criteria:

        Main Inclusion Criteria:

          1. Patients must not be eligible for another ongoing INC424 clinical trial.

          2. Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised
             International Standard Criteria, irrespective of JAK2 mutation status..

          3. 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 (assessment to
             occur at the Screening Visit).

             The prognostic factors, defined by the International Working Group are:

               -  Age > 65 years;

               -  Presence of constitutional symptoms (weight loss, fever, night sweats);

               -  Marked anemia (Hgb < 10g/dL)*;

               -  Leukocytosis (history of white blood cell (WBC) > 25 x109/L);

               -  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.

          4. 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.

          5. Patients must have a peripheral blood blast count of < 10%.

          6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1,
             or 2.

          7. Fedratinib pretreated patients with documented complete physical examination including
             full neurologic examination and cardiology assessment, thiamine level testing, and MRI
             of the brain if indicated based on signs or symptoms. Patients pretreated with
             fedratinib should have completed or be receiving thiamine supplementation according to
             the investigator's instructions.

        Main Exclusion Criteria:

          1. Patients eligible for hematopoietic stem cell transplantation (suitable candidate and
             a suitable donor is available).

          2. Patients with history of malignancy in past 3 years except for treated, early-stage
             squamous or basal cell carcinoma in situ.

          3. 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).

          4. Patients with cardiac disease which in the Investigator's opinion may jeopardize the
             safety of the patient or the compliance with the protocol.

          5. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal atrial
             fibrillation or recent (approximately 6 months) myocardial infarction or acute
             coronary syndrome.

          6. 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.

          7. Patients with known active hepatitis A, B, C or who are HIV-positive.

          8. Patients with inadequate bone marrow reserve at the Baseline visit as demonstrated by:

               -  Absolute neutrophil count (ANC) ≤ 1000/µL.

               -  Platelet count < 50,000/µL without the assistance of growth factors,
                  thrombopoietic factors or platelet transfusions.

          9. 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.

         10. In the case of ruxolitinib pretreated patients, ruxolitinib primary resistant patients
             defined as:

             • No spleen reduction within the first 12 weeks after front line therapy with
             ruxolitinib.

             AND

             • No reduction in symptoms within the first 12 weeks after first-line treatment with
             ruxolitinib.

         11. In the case of ruxolitinib pretreated patients, patients discontinuing ruxolitinib due
             to a Grade 4 Adverse event (AE) related or suspected to be related to ruxolitinib.