Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence
Condition: Primary Myelofibrosis; MPN-associated Myelofibrosis
MeSH terms: Neoplasms; Primary Myelofibrosis; Myeloproliferative Disorders
Intervention: Pomalidomide 0.5 mg; Placebo; Pomalidomide
Intervention description: Pomalidomide 0.5 mg capsule taken by mouth once daily. Immunomodulatory agent with demonstrated efficacy in the treatment of subjects with RBC-transfusion-dependence associated with MNP-associated myelofibrosis.; Placebo Comparator to active drug; Placebo capsule taken by mouth once daily; Pomalidomide 0.5 mg capsule taken by mouth once daily.
Intervention MeSH terms: Thalidomide; Pomalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 267.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelofibrosis; Post-polycythemia vera myelofibrosis; Post-essential thrombocythemia myelofibrosis; RBC-transfusion-dependence; Primary Myelofibrosis

Summary:

      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 in reversing anemia in Chinese
      with MPN-associated myelofibrosis and severe anemia not receiving RBC-transfusions (China
      extension study only)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Myeloproliferative-neoplasm (MPN)-associated myelofibrosis

          -  RBC-transfusion-dependence (global study):

               -  Average RBC-transfusion frequency ≥ 2 units/28 days over at least the 84 days
                  immediately prior to randomization. There must be no interval > 42 days without ≥
                  1 RBC-transfusion.

               -  Only RBC-transfusions given when the hemoglobin ≤ 90 g/L³ are scored in

        determining eligibility.

          -  RBC-transfusions due to bleeding are not scored in determining eligibility.

          -  RBC-transfusions due to chemotherapy-induced anemia are not scored in determining
             eligibility.

               -  Severe anemia (China-specific extension):

          -  ≥ 2 hemoglobin concentrations ≤ 80 g/L for ≥ 84 days immediately before the day of
             enrollment.

          -  No RBC-transfusion within 6 months prior to enrollment.

               -  Hemoglobin ≤ 130 g/L at randomization (global study); ≤ 80 g/L at enrollment in
                  the China-specific extension.

               -  Bone marrow biopsy within 6 months (global study only).

               -  Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin
                  and androgenic steroids

               -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 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 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 with the 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 (HIV) infection, active hepatitis B virus (HBV) or
             hepatitis C virus (HCV) infections.

          -  Prior treatment with pomalidomide.

          -  Allergic reaction or rash after treatment with thalidomide or lenalidomide

          -  Any of the following laboratory abnormalities:

               -  Neutrophils < 0.5x10^9 /L

               -  Platelets < 25 x 10^9 /L

               -  Estimated glomerular filtration rate (kidney function) < 30 mL/min/1.73 m²

               -  Aspartate aminotransferase (AST) and alanine transaminase (ALT) > 3.0 x upper
                  limit of normal (ULN)

               -  Total bilirubin ≥ 4 x 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