A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT00463385
Collaborator
(none)
88
11
4
81
8
0.1

Study Details

Study Description

Brief 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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
88 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Apr 1, 2007
Actual Primary Completion Date :
May 1, 2009
Actual Study Completion Date :
Dec 31, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Prednisone

Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.

Drug: Prednisone
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.

Drug: Placebo to pomalidomide
Matching pomalidomide placebo tablets

Experimental: Pomalidomide

Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of Cycle 12 and upon unblinding, participants 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, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

Drug: Pomalidomide
Other Names:
  • CC-4047
  • Pomalyst
  • Drug: Placebo to prednisone
    Matching prednisone placebo tablets

    Experimental: Pomalidomide 2 mg + Prednisone

    Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants 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, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

    Drug: Pomalidomide
    Other Names:
  • CC-4047
  • Pomalyst
  • Drug: Prednisone
    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.

    Experimental: Pomalidomide 0.5 mg + Prednisone

    Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants 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, were eligible to participate in the extension phase and continue to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

    Drug: Pomalidomide
    Other Names:
  • CC-4047
  • Pomalyst
  • Drug: Prednisone
    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.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment [Up to 168 days]

      A clinical responder was defined as either: 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 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 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.

    Secondary Outcome Measures

    1. Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment [Up to 336 days]

      A clinical responder was defined as either: 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 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 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.

    2. Time to the First Clinical Response [Up to 168 days]

      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: 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 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 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.

    3. Duration of First Clinical Response [Up to 40 months]

      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.

    4. Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores [Baseline and Cycle 6 (168 days).]

      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.

    5. Change From Baseline in Hemoglobin Concentration for Responders [Baseline, Cycle 6 (168 days)]

      Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment.

    6. Change From Baseline in Hemoglobin Concentration for Non-Responders [Baseline, Cycle 6 (168 days)]

      Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment.

    7. Change From Baseline in Likert Abdominal Pain Scale [Baseline and Cycle 6 (168 days)]

      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.

    8. Percentage of Participants With Clinical Response by Baseline JAK2 Assessment [Up to 336 days]

      Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.

    9. Number of Participants With Adverse Events (AEs) [From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).]

      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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA School of Medicine Hematology/Oncology Los Angeles California United States 90095
    2 Mayo Clinic Rochester Minnesota United States 55905
    3 Memorial Sloan-Kettering Cancer Center New York New York United States 10021-6007
    4 New York Presbyterian HospitalWeill Medical College of Cornell University New York New York United States 10021
    5 MD Anderson Cancer Center Leukemia Department Houston Texas United States 77030
    6 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109-4417
    7 Medical University of Vienna, Department of Internal Medicine, Hematology Vienna Austria A-1090
    8 Fondazione IRCCS Policlinico San Matteo Pavia Italy 27100
    9 IRCCS Policlinico S. Matteo Pavia Italy 27100
    10 Hematology DepartmentHospital Clinic Barcelona Spain 08036
    11 Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust Sheffield United Kingdom S10 2JF

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Robert Peter Gale, MD, PhD, Celgene Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00463385
    Other Study ID Numbers:
    • CC-4047-MMM-001
    First Posted:
    Apr 20, 2007
    Last Update Posted:
    Nov 20, 2019
    Last Verified:
    Nov 1, 2019

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Period Title: Overall Study
    STARTED 22 22 22 22
    Treated 22 22 19 22
    COMPLETED 0 0 0 0
    NOT COMPLETED 22 22 22 22

    Baseline Characteristics

    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone Total
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Total of all reporting groups
    Overall Participants 22 22 22 22 88
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    66.0
    68.0
    67.5
    69.5
    67.5
    Sex: Female, Male (Count of Participants)
    Female
    8
    36.4%
    5
    22.7%
    7
    31.8%
    9
    40.9%
    29
    33%
    Male
    14
    63.6%
    17
    77.3%
    15
    68.2%
    13
    59.1%
    59
    67%
    Race/Ethnicity, Customized (participants) [Number]
    White
    21
    95.5%
    22
    100%
    21
    95.5%
    22
    100%
    86
    97.7%
    Black
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    1
    1.1%
    Hispanic
    1
    4.5%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Janus kinase 2 (JAK2) Mutation (participants) [Number]
    Negative
    6
    27.3%
    7
    31.8%
    8
    36.4%
    8
    36.4%
    29
    33%
    Positive
    13
    59.1%
    11
    50%
    10
    45.5%
    9
    40.9%
    43
    48.9%
    Missing
    3
    13.6%
    4
    18.2%
    4
    18.2%
    5
    22.7%
    16
    18.2%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
    Grade 0
    12
    54.5%
    11
    50%
    6
    27.3%
    14
    63.6%
    43
    48.9%
    Grade 1
    8
    36.4%
    9
    40.9%
    10
    45.5%
    6
    27.3%
    33
    37.5%
    Grade 2
    2
    9.1%
    2
    9.1%
    5
    22.7%
    2
    9.1%
    11
    12.5%
    Missing
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    1
    1.1%
    Myelofibrosis with myeloid metaplasia Subtype (participants) [Number]
    Agnogenic Myeloid Metaplasia (AMM)
    16
    72.7%
    16
    72.7%
    16
    72.7%
    13
    59.1%
    61
    69.3%
    Postpolycythemic Myeloid Metaplasia (PPMM)
    3
    13.6%
    4
    18.2%
    4
    18.2%
    2
    9.1%
    13
    14.8%
    Postthromocythemic Myeloid Metaplasia (PTMM)
    3
    13.6%
    2
    9.1%
    2
    9.1%
    7
    31.8%
    14
    15.9%
    Time Since Myelofibrosis Diagnosis (years) [Median (Full Range) ]
    Median (Full Range) [years]
    1.5
    0.6
    1.1
    1.7
    1.1
    Red Blood Cell (RBC) Transfusion Dependence (participants) [Number]
    Yes
    12
    54.5%
    10
    45.5%
    9
    40.9%
    12
    54.5%
    43
    48.9%
    No
    10
    45.5%
    12
    54.5%
    13
    59.1%
    10
    45.5%
    45
    51.1%
    RBC Transfusion Burden (units/28 days) [Median (Full Range) ]
    Median (Full Range) [units/28 days]
    2.0
    1.0
    0.0
    2.0
    1.0

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment
    Description A clinical responder was defined as either: 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 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 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 Frame Up to 168 days

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat (MITT), defined as the patients who had a confirmed diagnosis of Myelofibrosis with myeloid metaplasia (MMM), received at least one dose of study drug, and participated in the study for at least 56 days.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 20 17 19 21
    Number (95% Confidence Interval) [percentage of participants]
    55.0
    250%
    23.5
    106.8%
    21.1
    95.9%
    47.6
    216.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Prednisone, Pomalidomide 2 mg
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.092
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Prednisone, Pomalidomide 2 mg + Prednisone
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.048
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Prednisone, Pomalidomide 0.5 mg + Prednisone
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.758
    Comments
    Method Fisher Exact
    Comments
    2. Secondary Outcome
    Title Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment
    Description A clinical responder was defined as either: 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 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 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 Frame Up to 336 days

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT), defined as as all patients who were randomized, independent of whether they received study treatment or not.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 22 22 22 22
    Number (95% Confidence Interval) [percentage of participants]
    50.0
    227.3%
    18.2
    82.7%
    18.2
    82.7%
    45.5
    206.8%
    3. Secondary Outcome
    Title Time to the First Clinical Response
    Description 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: 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 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 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.
    Time Frame Up to 168 days

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with a clinical response
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 11 4 4 10
    Median (Full Range) [weeks]
    0.3
    8.0
    10.1
    1.2
    4. Secondary Outcome
    Title Duration of First Clinical Response
    Description 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.
    Time Frame Up to 40 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with a clinical response.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 11 4 4 10
    Median (95% Confidence Interval) [months]
    3.7
    NA
    6.0
    10.6
    5. Secondary Outcome
    Title Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores
    Description 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.
    Time Frame Baseline and Cycle 6 (168 days).

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat patients with available data.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 9 7 3 12
    Physical Well-Being subscale
    0.6
    (1.50)
    0.4
    (6.42)
    5.3
    (4.04)
    2.3
    (2.26)
    Social/Family Well-Being subscale
    1.9
    (3.08)
    -1.9
    (2.59)
    1.7
    (3.79)
    0.9
    (6.84)
    Emotional Well-Being subscale
    1.3
    (3.32)
    0.0
    (4.76)
    -0.3
    (0.58)
    1.7
    (3.47)
    Functional Well-Being subscale
    0.9
    (4.14)
    -2.1
    (8.99)
    2.7
    (3.06)
    2.5
    (6.50)
    Anemia subscale
    1.2
    (9.47)
    2.3
    (21.34)
    19.3
    (18.93)
    5.8
    (8.85)
    Total FACT-An score
    2.3
    (12.42)
    1.6
    (36.51)
    27.3
    (25.74)
    11.4
    (13.51)
    6. Secondary Outcome
    Title Change From Baseline in Hemoglobin Concentration for Responders
    Description Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment.
    Time Frame Baseline, Cycle 6 (168 days)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat participants with a clinical response and available hemoglobin values at each time point.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 6 2 0 8
    Median (Full Range) [g/dL]
    1.4
    2.0
    -0.1
    7. Secondary Outcome
    Title Change From Baseline in Hemoglobin Concentration for Non-Responders
    Description Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment.
    Time Frame Baseline, Cycle 6 (168 days)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat participants with no clinical response and available hemoglobin values at each time point.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 3 5 5 6
    Median (Full Range) [g/dL]
    1.2
    0.1
    -0.8
    0.5
    8. Secondary Outcome
    Title Change From Baseline in Likert Abdominal Pain Scale
    Description 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.
    Time Frame Baseline and Cycle 6 (168 days)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat patients with available data.
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 10 7 3 12
    Mean (Standard Deviation) [units on a scale]
    0.3
    (1.83)
    -1.0
    (3.11)
    0.3
    (1.15)
    -0.1
    (1.68)
    9. Secondary Outcome
    Title Percentage of Participants With Clinical Response by Baseline JAK2 Assessment
    Description Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.
    Time Frame Up to 336 days

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population with non-missing JAK2 Baseline assessment results. The number of participants analyzed indicates the number of participants with a positive or negative JAK2 result for each treatment group respectively.
    Arm/Group Title Prednisone, Positive JAK2 Pomalidomide 2 mg, PositiveJAK2 Pomalidomide 2 mg + Prednisone, Positive JAK2 Pomalidomide 0.5 mg + Prednisone, Positive JAK2 Prednisone, Negative JAK2 Pomalidomide 2 mg, Negative JAK2 Pomalidomide 2 mg + Prednisone, Negative JAK2 Pomalidomide 0.5 mg + Prednisone, Negative JAK2
    Arm/Group Description Participants with a positive JAK2 result at Baseline received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants with a positive JAK2 result at Baseline received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants with a positive JAK2 result at Baseline received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants with a positive JAK2 result at Baseline received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants with a negative JAK2 result at Baseline received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants with a negative JAK2 result at Baseline received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants with a negative JAK2 result at Baseline received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants with a negative JAK2 result at Baseline received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 13 11 10 9 6 7 8 8
    Number [percentage of participants]
    46.2
    210%
    27.3
    124.1%
    30.0
    136.4%
    66.7
    303.2%
    50.0
    56.8%
    28.6
    NaN
    12.5
    NaN
    25.0
    NaN
    10. Secondary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description 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).
    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).

    Outcome Measure Data

    Analysis Population Description
    Safety population (all treated patients).
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    Measure Participants 22 22 19 22
    At least one AE
    20
    90.9%
    21
    95.5%
    18
    81.8%
    21
    95.5%
    At least one AE related to pomalidomide
    15
    68.2%
    17
    77.3%
    16
    72.7%
    15
    68.2%
    At least one AE related to prednisone
    10
    45.5%
    10
    45.5%
    11
    50%
    5
    22.7%
    At least one Grade 3-4 AE
    10
    45.5%
    14
    63.6%
    13
    59.1%
    15
    68.2%
    At least one Grade 3-4 AE related to pomalidomide
    6
    27.3%
    7
    31.8%
    11
    50%
    6
    27.3%
    At least one Grade 3-4 AE related to prednisone
    5
    22.7%
    2
    9.1%
    6
    27.3%
    3
    13.6%
    At least one SAE
    6
    27.3%
    10
    45.5%
    11
    50%
    8
    36.4%
    At least one SAE related to pomalidomide
    4
    18.2%
    6
    27.3%
    8
    36.4%
    3
    13.6%
    At least one SAE related to prednisone
    4
    18.2%
    3
    13.6%
    5
    22.7%
    3
    13.6%
    AE leading to discontinuation of pomalidomide
    7
    31.8%
    11
    50%
    5
    22.7%
    6
    27.3%
    AE leading to discontinuation of prednisone
    5
    22.7%
    7
    31.8%
    2
    9.1%
    1
    4.5%
    AE leading to a dose reduction of pomalidomide
    0
    0%
    2
    9.1%
    1
    4.5%
    1
    4.5%
    AE leading to a dose interruption of pomalidomide
    5
    22.7%
    9
    40.9%
    9
    40.9%
    7
    31.8%
    AE leading to a dose interruption of prednisone
    2
    9.1%
    8
    36.4%
    6
    27.3%
    3
    13.6%

    Adverse Events

    Time Frame From the first dose of the study drug through to 30 days after the last dose; up to the data cut-off date of 18 December 2013; up to 81 months
    Adverse Event Reporting Description
    Arm/Group Title Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Arm/Group Description Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.
    All Cause Mortality
    Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/22 (27.3%) 10/22 (45.5%) 11/19 (57.9%) 9/22 (40.9%)
    Blood and lymphatic system disorders
    Anaemia 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 2/22 (9.1%)
    Eosinophilia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Febrile Neutropenia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Haemolytic Anaemia 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Leukocytosis 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Neutropenia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Acquired Von Willebrand Disease 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Cardiac disorders
    Atrial Flutter 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Cardiac Failure 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Myocardial Infarction 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Atrial Fibrillation 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 1/22 (4.5%)
    Bradycardia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Cardiac Failure Acute 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Cardiac Failure Congestive 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Left Ventricular Dysfunction 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Right Ventricular Failure 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Endocrine disorders
    Hyperthyroidism 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Gastrointestinal disorders
    Diarrhoea 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Abdominal Pain 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Ascites 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Colitis 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Constipation 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Gastrointestinal Haemorrhage 0/22 (0%) 2/22 (9.1%) 1/19 (5.3%) 0/22 (0%)
    Lower Gastrointestinal Haemorrhage 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Varices Oesophageal 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    General disorders
    Asthenia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Chills 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Disease Progression 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Non-Cardiac Chest Pain 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Pyrexia 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Infections and infestations
    Pneumonia 1/22 (4.5%) 3/22 (13.6%) 3/19 (15.8%) 2/22 (9.1%)
    Septic Shock 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Bronchitis 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 1/22 (4.5%)
    Cellulitis 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Diverticulitis 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Lobar Pneumonia 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Lung Infection Pseudomonal 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Perirectal Abscess 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Respiratory Tract Infection 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Urinary Tract Infection Enterococcal 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Injury, poisoning and procedural complications
    Thoracic Vertebral Fracture 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Traumatic Brain Injury 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Investigations
    International Normalised Ratio Increased 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Hyperglycaemia 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Hyperuricaemia 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Cachexia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Failure To Thrive 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Fluid Retention 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Nervous system disorders
    Cerebral Haemorrhage 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Cerebrovascular Accident 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Cognitive Disorder 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Hepatic Encephalopathy 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Memory Impairment 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Psychiatric disorders
    Mental Status Changes 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Renal and urinary disorders
    Renal Failure 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Renal Failure Acute 0/22 (0%) 2/22 (9.1%) 1/19 (5.3%) 0/22 (0%)
    Renal Failure Chronic 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Lung Infiltration 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Pleural Effusion 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Pulmonary Embolism 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 0/22 (0%)
    Pulmonary Hypertension 0/22 (0%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Respiratory Failure 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 0/22 (0%)
    Vascular disorders
    Deep Vein Thrombosis 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 0/22 (0%)
    Hypotension 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Other (Not Including Serious) Adverse Events
    Prednisone Pomalidomide 2 mg Pomalidomide 2 mg + Prednisone Pomalidomide 0.5 mg + Prednisone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/22 (90.9%) 20/22 (90.9%) 17/19 (89.5%) 21/22 (95.5%)
    Blood and lymphatic system disorders
    Anaemia 2/22 (9.1%) 4/22 (18.2%) 3/19 (15.8%) 4/22 (18.2%)
    Thrombocytopenia 2/22 (9.1%) 5/22 (22.7%) 3/19 (15.8%) 3/22 (13.6%)
    Neutropenia 1/22 (4.5%) 5/22 (22.7%) 2/19 (10.5%) 3/22 (13.6%)
    Leukopenia 0/22 (0%) 3/22 (13.6%) 0/19 (0%) 2/22 (9.1%)
    Thrombocytosis 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 1/22 (4.5%)
    Cardiac disorders
    Palpitations 1/22 (4.5%) 0/22 (0%) 2/19 (10.5%) 0/22 (0%)
    Arrhythmia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Sinus Bradycardia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Tachycardia 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 1/22 (4.5%)
    Ear and labyrinth disorders
    Ear Congestion 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Tinnitus 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 0/22 (0%)
    Endocrine disorders
    Hypothyroidism 0/22 (0%) 3/22 (13.6%) 0/19 (0%) 0/22 (0%)
    Eye disorders
    Vision Blurred 3/22 (13.6%) 2/22 (9.1%) 4/19 (21.1%) 1/22 (4.5%)
    Eye Irritation 0/22 (0%) 1/22 (4.5%) 2/19 (10.5%) 1/22 (4.5%)
    Lacrimation Increased 0/22 (0%) 0/22 (0%) 2/19 (10.5%) 0/22 (0%)
    Periorbital Oedema 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 1/22 (4.5%)
    Gastrointestinal disorders
    Diarrhoea 5/22 (22.7%) 6/22 (27.3%) 7/19 (36.8%) 1/22 (4.5%)
    Abdominal Pain 4/22 (18.2%) 3/22 (13.6%) 1/19 (5.3%) 5/22 (22.7%)
    Nausea 4/22 (18.2%) 4/22 (18.2%) 3/19 (15.8%) 1/22 (4.5%)
    Abdominal Pain Upper 2/22 (9.1%) 2/22 (9.1%) 1/19 (5.3%) 3/22 (13.6%)
    Constipation 2/22 (9.1%) 2/22 (9.1%) 5/19 (26.3%) 4/22 (18.2%)
    Oral Pain 2/22 (9.1%) 0/22 (0%) 0/19 (0%) 1/22 (4.5%)
    Vomiting 2/22 (9.1%) 3/22 (13.6%) 1/19 (5.3%) 3/22 (13.6%)
    Flatulence 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)
    Gastrooesophageal Reflux Disease 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Abdominal Distension 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 3/22 (13.6%)
    Ascites 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Dyspepsia 0/22 (0%) 2/22 (9.1%) 5/19 (26.3%) 3/22 (13.6%)
    Gingival Bleeding 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Haematochezia 0/22 (0%) 1/22 (4.5%) 2/19 (10.5%) 1/22 (4.5%)
    Tongue Ulceration 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    General disorders
    Fatigue 6/22 (27.3%) 2/22 (9.1%) 6/19 (31.6%) 7/22 (31.8%)
    Oedema Peripheral 6/22 (27.3%) 8/22 (36.4%) 10/19 (52.6%) 10/22 (45.5%)
    Pyrexia 5/22 (22.7%) 7/22 (31.8%) 4/19 (21.1%) 6/22 (27.3%)
    Chills 2/22 (9.1%) 2/22 (9.1%) 1/19 (5.3%) 4/22 (18.2%)
    Asthenia 1/22 (4.5%) 3/22 (13.6%) 1/19 (5.3%) 4/22 (18.2%)
    Feeling Jittery 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Pain 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 2/22 (9.1%)
    Gait Disturbance 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Oedema 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/22 (4.5%) 0/22 (0%) 2/19 (10.5%) 0/22 (0%)
    Immune system disorders
    Seasonal Allergy 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Infections and infestations
    Upper Respiratory Tract Infection 3/22 (13.6%) 2/22 (9.1%) 1/19 (5.3%) 2/22 (9.1%)
    Pneumonia 2/22 (9.1%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Influenza 1/22 (4.5%) 1/22 (4.5%) 2/19 (10.5%) 2/22 (9.1%)
    Cystitis 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 1/22 (4.5%)
    Enterococcal Sepsis 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Eye Infection 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Nasopharyngitis 0/22 (0%) 0/22 (0%) 0/19 (0%) 3/22 (13.6%)
    Respiratory Tract Infection 0/22 (0%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)
    Urinary Tract Infection 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 1/22 (4.5%)
    Injury, poisoning and procedural complications
    Contusion 0/22 (0%) 2/22 (9.1%) 2/19 (10.5%) 1/22 (4.5%)
    Excoriation 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Laceration 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Investigations
    Heart Rate Increased 2/22 (9.1%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Weight Decreased 1/22 (4.5%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)
    Cardiac Murmur 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 2/22 (9.1%)
    Metabolism and nutrition disorders
    Decreased Appetite 1/22 (4.5%) 1/22 (4.5%) 0/19 (0%) 3/22 (13.6%)
    Gout 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 1/22 (4.5%)
    Hyperglycaemia 0/22 (0%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)
    Hyperuricaemia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 3/22 (13.6%)
    Hypokalaemia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 2/22 (9.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/22 (13.6%) 3/22 (13.6%) 1/19 (5.3%) 2/22 (9.1%)
    Muscle Spasms 3/22 (13.6%) 1/22 (4.5%) 6/19 (31.6%) 5/22 (22.7%)
    Pain In Extremity 2/22 (9.1%) 4/22 (18.2%) 2/19 (10.5%) 3/22 (13.6%)
    Back Pain 1/22 (4.5%) 2/22 (9.1%) 2/19 (10.5%) 1/22 (4.5%)
    Bone Pain 1/22 (4.5%) 3/22 (13.6%) 0/19 (0%) 0/22 (0%)
    Myalgia 1/22 (4.5%) 2/22 (9.1%) 1/19 (5.3%) 4/22 (18.2%)
    Muscular Weakness 0/22 (0%) 1/22 (4.5%) 0/19 (0%) 3/22 (13.6%)
    Musculoskeletal Chest Pain 0/22 (0%) 0/22 (0%) 2/19 (10.5%) 0/22 (0%)
    Osteoarthritis 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Nervous system disorders
    Dizziness 4/22 (18.2%) 2/22 (9.1%) 6/19 (31.6%) 8/22 (36.4%)
    Paraesthesia 4/22 (18.2%) 2/22 (9.1%) 3/19 (15.8%) 4/22 (18.2%)
    Burning Sensation 3/22 (13.6%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)
    Headache 2/22 (9.1%) 2/22 (9.1%) 0/19 (0%) 4/22 (18.2%)
    Dysgeusia 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Hypoaesthesia 1/22 (4.5%) 1/22 (4.5%) 1/19 (5.3%) 2/22 (9.1%)
    Memory Impairment 1/22 (4.5%) 1/22 (4.5%) 2/19 (10.5%) 0/22 (0%)
    Aphonia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Balance Disorder 0/22 (0%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)
    Dementia Alzheimer's Type 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Migraine 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Tremor 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Psychiatric disorders
    Insomnia 4/22 (18.2%) 2/22 (9.1%) 2/19 (10.5%) 3/22 (13.6%)
    Depression 1/22 (4.5%) 2/22 (9.1%) 1/19 (5.3%) 0/22 (0%)
    Confusional State 0/22 (0%) 1/22 (4.5%) 2/19 (10.5%) 0/22 (0%)
    Mental Status Changes 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 0/22 (0%)
    Personality Change 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Renal and urinary disorders
    Pollakiuria 1/22 (4.5%) 0/22 (0%) 2/19 (10.5%) 0/22 (0%)
    Haematuria 0/22 (0%) 1/22 (4.5%) 1/19 (5.3%) 0/22 (0%)
    Urinary Incontinence 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 7/22 (31.8%) 7/22 (31.8%) 3/19 (15.8%) 6/22 (27.3%)
    Cough 6/22 (27.3%) 6/22 (27.3%) 4/19 (21.1%) 8/22 (36.4%)
    Nasal Congestion 3/22 (13.6%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Epistaxis 1/22 (4.5%) 2/22 (9.1%) 5/19 (26.3%) 3/22 (13.6%)
    Pulmonary Hypertension 1/22 (4.5%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Dysphonia 0/22 (0%) 1/22 (4.5%) 2/19 (10.5%) 2/22 (9.1%)
    Dyspnoea Exertional 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Oropharyngeal Pain 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 3/22 (13.6%)
    Pleural Effusion 0/22 (0%) 2/22 (9.1%) 1/19 (5.3%) 0/22 (0%)
    Pleuritic Pain 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Skin and subcutaneous tissue disorders
    Increased Tendency To Bruise 2/22 (9.1%) 0/22 (0%) 0/19 (0%) 0/22 (0%)
    Night Sweats 2/22 (9.1%) 2/22 (9.1%) 1/19 (5.3%) 5/22 (22.7%)
    Ecchymosis 1/22 (4.5%) 3/22 (13.6%) 1/19 (5.3%) 1/22 (4.5%)
    Pruritus 1/22 (4.5%) 1/22 (4.5%) 2/19 (10.5%) 3/22 (13.6%)
    Rash 1/22 (4.5%) 8/22 (36.4%) 3/19 (15.8%) 3/22 (13.6%)
    Dry Skin 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Erythema 0/22 (0%) 2/22 (9.1%) 0/19 (0%) 4/22 (18.2%)
    Rash Pruritic 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Skin Odour Abnormal 0/22 (0%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Vascular disorders
    Hypertension 1/22 (4.5%) 0/22 (0%) 1/19 (5.3%) 0/22 (0%)
    Hypotension 1/22 (4.5%) 2/22 (9.1%) 0/19 (0%) 0/22 (0%)
    Haematoma 0/22 (0%) 0/22 (0%) 0/19 (0%) 2/22 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.

    Results Point of Contact

    Name/Title Associate Director, Clinical Trials Disclosure
    Organization Celgene Corporation
    Phone 1-888-260-1599
    Email clinicaltrialdisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00463385
    Other Study ID Numbers:
    • CC-4047-MMM-001
    First Posted:
    Apr 20, 2007
    Last Update Posted:
    Nov 20, 2019
    Last Verified:
    Nov 1, 2019