A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

A Phase 2, Prospective, Randomized, Multicenter, Double-blind, Active-control, Parallel-group Study to Determine the Safety of and to Select a Treatment Regimen of CC-4047 (Pomalidomide) Either as Single-agent or in Combination With Prednisone to Study Further in Subjects With Myelofibrosis With Myeloid Metaplasia

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).

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.

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