Study to Determine the Safety and Efficacy of Ruxolitinib (INCB018424) in Patients With Polycythemia Vera or Essential Thrombocythemia

• Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) [ Time Frame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3 ] [ Designated as safety issue: Yes ]

  For a confirmed response all criteria must have been sustained for at least 2 months.

  CR:

  • Hematocrit < 45% in men and < 42% in women
  • No phlebotomy for 1 month
  • No palpable splenomegaly
  • White blood cells < 10 x 10^9/L with normal differential and platelets < 400 x 10^9/L
  • No sustained leucopenia or thrombocytopenia (>2 weeks)
  • No systemic PV symptoms (pruritus, night sweats, bone pain, fever, weight loss)

  PR:

  • Hematocrit < 45% in men and < 42% in women
  • 50% reduction in phlebotomy requirements from 6 months before treatment started
  • 50% reduction in palpable splenomegaly
  
  
• Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) [ Time Frame: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3. ] [ Designated as safety issue: Yes ]

  For a confirmed response all criteria must have been sustained for at least 2 months.

  Complete Clinical Response:

  • Platelet count < 400 x 10^9/L
  • White blood cell count < 10 x 10^9/L with normal differential and Hematocrit ≤ upper limit of normal
  • Absence of sustained (> 2 weeks) anemia or leucopenia based on institutional normal ranges
  • Absence of systemic ET symptoms (pruritus, bone pain, weakness, night sweats, paresthesias)
  • Absence of palpable splenomegaly

  Partial Clinical Response:

  • Platelet count < 400 x 10^9/L
  • 50% reduction in palpable splenomegaly
  
  

• Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks [ Time Frame: Baseline and Week 12 (Cycle 4, Day 1) ] [ Designated as safety issue: No ]

  The individual components of clinical response included:

  • Hematocrit (Hct) < 45% without phlebotomy
  • Absence of palpable splenomegaly
  • 50% reduction in spleen size
  • Platelet count ≤ 400 x 10^9/L
  • White blood cell (WBC) count ≤ 10 x 10^9/L
  
  
• Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks [ Time Frame: Baseline and Week 24 (Cycle 7, Day 1) ] [ Designated as safety issue: No ]

  The individual components of clinical response included:

  • Hematocrit (Hct) < 45% without phlebotomy
  • Absence of palpable splenomegaly
  • 50% reduction in spleen size
  • Platelet count ≤ 400 x 10^9/L
  • White blood cell (WBC) count ≤ 10 x 10^9/L
  
  
• Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks [ Time Frame: Baseline and Week 36 (Cycle 10, Day 1) ] [ Designated as safety issue: No ]

  The individual components of clinical response included:

  • Hematocrit (Hct) < 45% without phlebotomy
  • Absence of palpable splenomegaly
  • 50% reduction in spleen size
  • Platelet count ≤ 400 x 10^9/L
  • White blood cell (WBC) count ≤ 10 x 10^9/L
  
  
• Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks [ Time Frame: Baseline and 4 weeks (Cycle 2, Day 1) ] [ Designated as safety issue: No ]

  The individual components of clinical response included:

  • Platelet count ≤ 400 x 10^9/L
  • White blood cell (WBC) count ≤ 10 x 10^9/L
  • 50% reduction in spleen size
  • Absence of palpable splenomegaly
  
  
• Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks [ Time Frame: Baseline and 24 weeks (Cycle 7, Day 1) ] [ Designated as safety issue: No ]

  The individual components of clinical response included:

  • Platelet count ≤ 400 x 10^9/L
  • White blood cell (WBC) count ≤ 10 x 10^9/L
  • 50% reduction in spleen size
  • Absence of palpable splenomegaly
  
  
• Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks [ Time Frame: Baseline and 36 weeks (Cycle 10, Day 1) ] [ Designated as safety issue: No ]

  The individual components of clinical response included:

  • Platelet count ≤ 400 x 10^9/L
  • White blood cell (WBC) count ≤ 10 x 10^9/L
  • 50% reduction in spleen size
  • Absence of palpable splenomegaly
  
  
• Change From Baseline to Week 4 in Polycythemia Vera Symptoms [ Time Frame: Baseline and Week 4 (Cycle 2, Day 1) ] [ Designated as safety issue: No ]

  Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms.

  For patients with Polycythemia Vera, queried symptoms included fever, itching/pruritus, bone pain and night sweats.

  
  
• Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms [ Time Frame: Baseline and Week 4 (Cycle 2, Day 1) ] [ Designated as safety issue: No ]

  Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms.

  For patients with essential thrombocythemia, queried symptoms included itching/pruritus, bone pain, night sweats, paresthesias (tingling or numbness), and weakness.

  
  
• Change From Baseline to Week 4 in Health-related Quality of Life [ Time Frame: Baseline and Week 4 (Cycle 2, Day 1) ] [ Designated as safety issue: No ]
  Health-related Quality of Life was assessed using the Global Health Status/Quality of Life Scale of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This scale ranges from 0 to 100, with higher scores indicating higher quality of life.
  
  

The study consisted of a 2-stage design, which included a dose-ranging phase (during which patients received treatment at their randomized dose) and an expansion phase (after adjustment of dose/regimen to achieve an optimal balance of efficacy and safety). During the dose-ranging phase, patients in each disease group (PV or ET) were randomly assigned in a 1:1:1 ratio independent of each other to receive 1 of 3 treatment regimens with Ruxolitinib, 10 mg twice daily (bid), 25 mg bid, or 50 mg once daily (qd). After patients completed 2 cycles of treatment with Ruxolitinib at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis using their discretion in order to achieve an optimal balance of efficacy and safety. During the expansion phase (ie, after optimization of dose), additional patients with PV or ET were enrolled to receive Ruxolitinib at the dose that was selected upon review of data from the dose-ranging phase. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.