Phase-3 Double-Blind, Placebo-Controlled Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence Myelofibrosis and RBC-Transfusion-Dependence (RESUME)

• Duration of RBC-transfusion-independence [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
• Time to becoming RBC-transfusion-independent - every 28 days [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Healthcare resource utilization [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
• EQ-5D Health Outcome Assessment [ Time Frame: Day 1, 85, 169 and treatment discontinuation ] [ Designated as safety issue: No ]
• FACT-An Quality of Life (QoL) Assessment [ Time Frame: D1, D84 and every 84 days while on treatment and treatment discontinuation ] [ Designated as safety issue: No ]
• Frequency of AE's [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
• Survival - alive or dead [ Time Frame: 6 months, 2 years and 5 years after the last subject is randomized ] [ Designated as safety issue: Yes ]

• Duration of RBC-transfusion-independence [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
• Time to becoming RBC-transfusion-independent - every 28 days [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Healthcare resource utilization [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
• EQ-5D Health Outcome Assessment [ Time Frame: Day 1, 85, 169 and treatment discontinuation ] [ Designated as safety issue: No ]
• FACT-An Quality of Life (QoL) Assessment [ Time Frame: D1, D84 and every 84 days while on treatment and treatment discontinuation ] [ Designated as safety issue: No ]
• Frequency of AE's [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
• Survival - alive or dead [ Time Frame: 6 months, 2 years and 5 years after the last subject is randomized ] [ Designated as safety issue: Yes ]
  Survival - alive or dead at 6 months, 2 years and 5 years after the last subject is randomized

The objective of this study is to determine whether pomalidomide is safe and effective in reversing red blood cell (RBC)-transfusion-dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. (Global Study) and to describe the frequency of anemia response to pomalidomide in Chinese subjects with MPN-associated myelofibrosis and severe anemia not receiving REC-transfusions (China Extension Study only)

Study sites in China will also participate in a China-specific, single-arm, open label extension of the current study. Subjects will have myeloproliferative neoplasm (MPN)-associated myelofibrosis and severe anemia and not be receiving red blood cell (RBC)-transfusions. Eligible subjects will receive pomalidomide (0.5 mg/day) and will be evaluated on a schedule parallel to that of the global study.

• China Extension Study Description: Multicenter,single-arm, open-label study to describe safety and efficacy of pomalidomide in subjects with MPN-associated myelofibrosis and severe anemia, not receiving RBC-transfusions.
• China Extension Study Primary Outcome: Describe the frequency of anemia response to pomalidomide in Chinese subjects with MPN-associated myelofibrosis and severe anemia, not receiving RBC-transfusions.

• China Extension Study Secondary Outcomes:

  1. Duration of anemia response (hemoglobin increase ≥15 g/L)
  2. Time to anemia response (beginning of a hemoglobin increase ≥15 g/L)
  3. Survival
  4. Frequency of adverse events (AEs)
• China Extension Estimated Enrollment: 50-75 Subjects
• China Extension Enrollment Interval: approximately 9 months to begin after closure of enrollment into the global study.
• China Extension Duration: 5 years after last subject enrolled
• China Extension Analysis: Approximately 6 months after enrollment of the last subject.

• China Extension Inclusion Criteria (Same as for global study except for items 3 and 4 noted below):

  • 3).Severe Anemia: ≥2 hemoglobin levels ≤80 g/L for ≥84 days immediately before the day of enrollment (anticipated first day of treatment). No RBC-transfusion within 6 months prior to enrollment.
  • 4).Hemoglobin ≤80 g/L at enrollment.
• China Extension Exclusion Criteria (Same as for global study)

• Drug: Pomalidomide
  pomalidomide 0.5 mg capsule taken by mouth once daily or one placebo capsule taken by mouth once daily. Subjects may take capsules for at least 168 days unless there are side-effects, progression of MPN-associated myelofibrosis or recurrence of RBC-transfusion-dependence.
  Other Name: Pomalidomide
• Other: Placebo
  Placebo Comparator to active drug

• Experimental: Pomalidomide
  pomalidomide 0.5 mg capsule taken by mouth once daily or one placebo capsule taken by mouth once daily. Subjects may take capsules for at least 168 days unless there are side-effects, progression of MPN-associated myelofibrosis or recurrence of RBC-transfusion-dependence.
  Intervention: Drug: Pomalidomide
• Placebo Comparator: Placebo
  Placebo
  Intervention: Other: Placebo

Inclusion Criteria:

• Age ≥18 years
• Myeloproliferative-neoplasm (MPN)-associated myelofibrosis
• RBC-transfusion-dependence
• Bone marrow biopsy within 6 months
• Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin and androgenic steroids
• Eastern Cooperative Oncology Group (ECOG) performance score ≤2.
• Agree to follow pregnancy precautions as required by the protocol.
• Agree to receive counseling related to teratogenic and other risks of pomalidomide
• Agree not to donate blood or semen

Exclusion Criteria:

• Prior blood cell or bone marrow allotransplant.
• Use of drugs to treat MPN-associated myelofibrosis ≤30 - 42 days before starting study drug.
• Treatment with erythropoietin or androgenic steroids ≤84 days before starting study drug.
• Anemia due to reasons other than MPN-associated myelofibrosis.
• Pregnant or lactating females.
• More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks

• Prior history of malignancies,other than the disease being studied, unless the subject has been free of the malignancy for ≥5 years. Following exceptions:

  • Carcinoma in situ of the cervix
  • Carcinoma in situ of the breast
  • Incidental histologic finding of prostate cancer (T 1a or T 1b using TNM [tumor, nodes, metastasis] clinical staging system)
• Human Immunodeficiency Virus infection (HIV-infection), active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
• Prior treatment with pomalidomide.
• Allergic reaction or rash after treatment with thalidomide or lenalidomide

• Any of the following laboratory abnormalities:

  • Neutrophils <0.5x10e9 /L
  • Platelets <25 x 10e9 /L
  • Estimated glomerular filtration rate (kidney function) <30 mL/min/1.73m^2
  • Aspartate aminotransferase (AST) and Alanine transaminase (ALT) >3.0 x upper limit of normal
  • Total bilirubin ≥4 x Upper Limit of Normal (ULN);
• Uncontrolled hyperthyroidism or hypothyroidism.
• Deep venous thrombosis (DVT) or pulmonary embolus (PE) <6 months before starting study drug
• Clinically-important heart disease within the past 6 months