A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia
Condition: Myelofibrosis With Myeloid Metaplasia; Myeloid Metaplasia; Myelofibrosis
MeSH terms: Primary Myelofibrosis; Metaplasia
Intervention: Pomalidomide; Prednisone; Placebo to pomalidomide; Placebo to prednisone
Intervention description: Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.; Matching pomalidomide placebo tablets; Matching prednisone placebo tablets
Intervention MeSH terms: Thalidomide; Prednisone; Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Celgene; CC-4047; Myelofibrosis; myelofibrosis with myeloid metaplasia; myeloid metaplasia; JAK2; CC-4047-MMM-001; Prednisone; Phase II; pomalidomide; bone marrow histology; imids; MMM; Ashkenazi Jewish Population; exposure to Thorotrast; exposure to solvents (benzene and toluene); acute megakaryocytic leukemia; history of polycythemia vera

Summary:

      The purpose of this study is to determine the safety of and to select a treatment regimen of
      pomalidomide (CC-4047) either as single-agent or in combination with prednisone to study
      further in patients with myelofibrosis with myeloid metaplasia (MMM).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must sign an informed consent form

          -  Must be >18 years of age

          -  Must be diagnosed with myelofibrosis

          -  Eligibility is based on local pathology review of bone marrow aspirate and biopsy

          -  Screening total hemoglobin level < 10g/dL or transfusion-dependent anemia defined as
             per International Working Group (IWG) criteria.

          -  Must have adequate organ function as demonstrated by the following ≤ 14 days prior to
             starting study drug:

               -  Alanine aminotransferase (ALT; SGPT)/aspartate aminotransferase (AST; SGOT) ≤ 3 x
                  upper limit of normal (ULN), [unless upon judgment of the treating physician, it
                  is believed to be due to extra-medullary hematopoiesis (EMH)].

               -  Total Bilirubin <3x ULN or Direct Bilirubin <2 x ULN

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Absolute neutrophil count ≥ 1,000/μL (≥ 1 x 10^9/L).

               -  Platelet count ≥ 50,000 /μL (≥ 50 x 10^9/L).

          -  Patients must be willing to receive transfusion of blood products

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at
             screening.

          -  Must be able to adhere to the study visit schedule and other protocol requirements.

          -  No active malignancies with the exception of controlled prostate cancer, basal cell or
             squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

          -  Must agree to follow pregnancy precautions as required per the protocol

        Exclusion Criteria:

          -  Known positive status for human immunodeficiency virus (HIV), hepatitis B carrier, or
             active hepatitis C infection.

          -  Previous untoward reaction to corticosteroid (specifically, prednisone) therapy that
             was severe enough, in the opinion of the treating physician, to preclude study
             participation.

          -  The use of any growth factors, cytotoxic chemotherapeutic agents (e.g. hydroxyurea and
             anagrelide), corticosteroids, or experimental drug or therapy within a minimum of 28
             days of starting CC-4047 and/or lack of recovery from all toxicity from previous
             therapy to grade 1 or better (e.g. alpha interferon may require 84 days of longer or
             washout).

          -  Prior therapy with CC-4047 or, lenalidomide or thalidomide for Myelofibrosis with
             myeloid metaplasia (MMM). (Prior prednisone use as a therapy for MMM is allowed, but
             not within 28 days of starting CC-4047).

          -  History of deep vein thrombosis or pulmonary embolism within one year of starting
             study medication.

          -  Any serious medical condition or psychiatric illness that would prevent, (as judged by
             the treating physician) the subject from signing the informed consent form or any
             condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Pregnant or lactating females