A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

• Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment [ Time Frame: Up to 168 days ] [ Designated as safety issue: No ]

  A clinical responder was defined as either:

  1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or
  2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or
  3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable.

  Participants who discontinued the study early without achieving clinical response were counted as non-responders.

  
  

• Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment [ Time Frame: Up to 336 days ] [ Designated as safety issue: No ]

  A clinical responder was defined as either:

  1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or
  2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or
  3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable.

  Participants who discontinued the study early without achieving clinical response were counted as non-responders.

  
  
• Time to the First Clinical Response [ Time Frame: Up to 168 days ] [ Designated as safety issue: No ]

  The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as:

  Start date of the first clinical response - the first study drug date +1.

  A clinical responder was defined as either:

  1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or
  2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or
  3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable.
  
  
• Duration of First Clinical Response [ Time Frame: Up to 40 months ] [ Designated as safety issue: No ]

  For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administrated at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment.

  For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the earlier of the date of a hemoglobin increase of < 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement.

  Kaplan-Meier methodology was used.

  
  
• Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores [ Time Frame: Baseline and Cycle 6 (168 days). ] [ Designated as safety issue: No ]

  The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life.

  • Physical Well-being consists of 7 questions, the subscale score ranges from 0-28;
  • Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28;
  • Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24;
  • Functional Well-Being consists of 7 questions, the subscale score ranges from 0-28;
  • Anemia subscale consists of 20 questions, the subscale score ranges from 0-80;
  • Total FACT-An score ranges from 0-188.
  
  
• Change From Baseline in Hemoglobin Concentration for Responders [ Time Frame: Baseline, Cycle 6 (168 days) ] [ Designated as safety issue: No ]
  Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment.
  
  
• Change From Baseline in Hemoglobin Concentration for Non-Responders [ Time Frame: Baseline, Cycle 6 (168 days) ] [ Designated as safety issue: No ]
  Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment.
  
  
• Change From Baseline in Likert Abdominal Pain Scale [ Time Frame: Baseline and Cycle 6 (168 days) ] [ Designated as safety issue: No ]
  Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable.
  
  
• Percentage of Participants With Clinical Response by Baseline JAK2 Assessment [ Time Frame: Up to 336 days ] [ Designated as safety issue: No ]
  Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.
  
  
• Number of Participants With Adverse Events (AEs) [ Time Frame: From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months). ] [ Designated as safety issue: Yes ]

  A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above).

  The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale:

  Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death.

  The Investigator determined the relationship between study drug and the occurrence of an AE as "Not Related" or "Related" (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa).

  
  

Participants received study treatment in the Double Blind Treatment Phase for up to 12 cycles (336 days; 12 cycles of 28 days each). Participants who completed the Double-Blind Treatment Phase were unblinded and, if receiving pomalidomide and determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, could have continued on their current dose of pomalidomide until disease progression. Participants receiving placebo were discontinued from the study.