Efficacy and Safety of Ruxolitinib in the Treatment of Anemic Myelofibrosis Patients.
Condition: Primary Myelofibrosis; Post-Polycythemia Vera-Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis
MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: ruxolitinib
Intervention description: Ruxolitinib was supplied in 5 mg tablets to be taken orally approximately 12 hours apart (morning and night)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ruxolitinib; anemia; Primary Myelofibrosis; PMF; Post-Polycythemia Vera-Myelofibrosis; PPV-MF; Post-Essential Thrombocythemia Myelofibrosis; PET-MF; adult; INC424

Summary:

      This was a study of treatment with ruxolitinib in patients who presented with transfusion
      dependent or independent anemia. Starting dose was 10 mg BID. This dose was maintained for
      the first 12 weeks of the study and up-titrated thereafter unless the subject met criteria
      for dose hold or dose reduction
    

Eligibility criteria:

        Inclusion Criteria:

        Written informed consent must be obtained prior to any screening procedures.

          1. Male or female patients aged ≥ 18 years of age.

          2. Patients must have been diagnosed with PMF, according to the 2016 revised
             International Standard Criteria, PPV MF or PET-MF, irrespective of JAK2 mutation
             status.

          3. Patients must have had palpable splenomegaly that is equal to or greater than 5 cm
             below the left costal margin.

          4. Patients must have had hemoglobin less than 10 g/dL

          5. Patients must have had a history of transfusions must have a documented transfusion
             record in the previous 12 weeks to baseline.

          6. Patients must have had ECOG performance status of 0, 1, or 2.

          7. Patients must have had a peripheral blood blast percentage count of < 10%.

          8. Patients must have recovered or stabilized sufficiently from any adverse drug
             reactions associated with prior treatments before beginning treatment with
             ruxolitinib.

        Exclusion Criteria:

          1. Patients who had prior treatment with any JAK1 or JAK2 inhibitor.

          2. Patients who had known hypersensitivity to ruxolitinib or other JAK1/JAK2 inhibitors,
             or to their excipients.

          3. Patients who had been eligible for hematopoietic stem cell transplantation (suitable
             candidate and a suitable donor is available).

          4. Patients who had inadequate bone marrow reserve at baseline as demonstrated by at
             least one of the following:

               1. ANC that is ≤ 1,000/µL.

               2. Platelet count that is <50,000/µL without the assistance of growth factors,
                  thrombopoietic factors or platelet transfusions.

               3. Hemoglobin count that is ≤ 6.5 g/dL despite transfusions.

          5. Patients who had severely impaired renal function defined by: Creatinine clearance
             less than 30 mL/min.

          6. Patients who had inadequate liver function defined by any of these:

               1. Total bilirubin ≥ 2.5 x ULN and subsequent determination of direct bilirubin ≥
                  2.5 x ULN;

               2. Alanine aminotransferase (ALT) > 2.5 x ULN;

               3. Aspartate aminotransferase (AST) > 2.5 x ULN.

          7. Patients who were being treated concurrently with a strong (potent) systemic inhibitor
             or inducer of CYP3A4 at the time of Screening.

          8. Presence of active bacterial, fungal, parasitic, or viral infection which requires
             therapy.

          9. Known history of human immunodeficiency virus (HIV) infection or other
             immunodeficiency syndromes such as X-linked agammaglobulinemia and common variable
             immune deficiency.

         10. Acute viral hepatitis or active chronic hepatitis B or C infection. Patients with
             inactive chronic infection (without viral replication) can be enrolled

         11. History of progressive multifocal leuko-encephalopathy.

         12. Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of ruxolitinib .

         13. History or current diagnosis of uncontrolled or significant cardiac disease, including
             any of the following:

               1. Myocardial infarction within last 6 months

               2. Uncontrolled congestive heart failure

               3. Unstable angina within last 6 months

               4. Clinically significant (symptomatic) cardiac arrhythmias (e.g. bradyarrhythmias,
                  sustained ventricular tachycardia, and clinically significant second or third
                  degree AV block without a pacemaker)

         14. Significant concurrent, uncontrolled medical condition which, in the investigator's
             opinion, would have jeopardized the safety of the patient or compliance with the
             protocol.

         15. Patients who were undergoing treatment with another investigational medication or had
             been treated with an investigational medication within 30 days or 5 half-lives
             (whichever is longer) prior to the first dose of study drug.

         16. Patients who had a history of malignancy in the past 3 years, except for treated early
             stage squamous or basal cell carcinoma.

         17. Patients who were unable to comprehend or are unwilling to sign an ICF.

         18. Pregnant or nursing (lactating) women

         19. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they were using highly effective methods of contraception
             throughout the study duration inclusive of 30 day safety follow up.