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A Study Being Conducted at Multiple Locations to Compare Safety and Efficacy of Three Different Regimens; (1) High-Dose Lenalidomide; (2) Lenalidomide + Azacitidine; or (3) Azacitidine in Subjects ≥ 65 Years With Newly-Diagnosed Acute Myeloid Leukemia

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01358734
Collaborator
(none)
88
Enrollment
30
Locations
3
Arms
72.6
Actual Duration (Months)
2.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study aim is to compare safety and efficacy of high-dose lenalidomide regimen, sequential azacitidine and lenalidomide and an azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia (AML).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

On September 11, 2013, randomization into the continuous 50 mg lenalidomide only arm was temporarily suspended based on review of the data from the first 13 participants and a high rate of discontinuation (11/13 participants). The Data Monitoring Committee assessed the study data on September 20, 2013 and reported no safety concerns. The high rate of early discontinuation is inconsistent with the treatment duration required for testing the study primary endpoint of survival at one year. Consequently, Celgene has decided not to reopen the lenalidomide only arm.

Study Design

Study Type:
Interventional
Actual Enrollment :
88 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Randomized, Open-label, Parallel-group Study of a Lenalidomide (Revlimid®) Regimen or a Sequential Azacitidine (Vidaza®) Plus Lenalidomide (Revlimid®) Regimen Versus an Azacitidine (Vidaza®) Regimen for Therapy of Older Subjects With Newly Diagnosed Acute Myeloid Leukemia
Actual Study Start Date :
Apr 27, 2012
Actual Primary Completion Date :
May 19, 2015
Actual Study Completion Date :
May 15, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lenalidomide in combination with azacitidine

Repeated cycles of azacitidine 75 mg/m^2/day subcutaneous (SC) on Days 1-7 and lenalidomide 50 mg/day by mouth (PO) on Days 8-28 followed by a 14-day break plus best supportive care

Drug: Azacitidine
Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Other Names:
  • Vidaza

    • Drug: Lenalidomide
    Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily
    Other Names:
  • Revlimid®
  • CC-5013

    • Other: Best Supportive Care (BSC)
    The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support
    Experimental: Lenalidomide - single agent

    Lenalidomide 50 mg PO daily for 28 days for the first 2 cycles and lenalidomide 25 mg daily for 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg daily PO plus best supportive care

    Drug: Lenalidomide
    Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily
    Other Names:
  • Revlimid®
  • CC-5013

    • Other: Best Supportive Care (BSC)
    The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support
    Experimental: Azacitidine-single agent

    Repeated cycles of azacitidine 75mg/m^2/day subcutaneous on Days 1-7 followed by a 21-day break plus best supportive care

    Drug: Azacitidine
    Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
    Other Names:
  • Vidaza

    • Other: Best Supportive Care (BSC)
    The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support

    Outcome Measures

    Primary Outcome Measures

    1. Kaplan Meier Estimates for One Year Survival [Up to 24 months]

      One-year survival rate was defined as all deaths within one year from the date of randomization. All others censored at the at year 1 or date of discontinuation

    2. Overall Survival [From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)]

      Overall Survival reported at the end of the study are for those participants who were alive at the end of the study

    Secondary Outcome Measures

    1. Percentage of Participants With a Complete Response or Morphologic Incomplete Response. [Complete Response or Morphologic Incomplete Response data not analyzed.]

      Based on IWG response criteria for AML. Complete remission (CR), morphologic complete remission (CR) was defined as < 5% bone marrow blasts, an absolute neutrophil count ≥ 1 x 10^9/L, platelets ≥100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. Morphologic CR with incomplete blood count recovery (CRi) was defined as a morphologic complete remission but the ANC count may be <1 x 10^9/L and/or the platelet count may be <100 x 10^9/L. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    2. Duration of Remission (DoR) [Duration of Remission (DoR) time frame not analyzed.]

      Duration of remission was defined as the time from the date of CR or CRi until relapse. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    3. Cytogenetic Complete Remission Rate (CRc) [Cytogenetic Complete Remission timeframe was not analyzed.]

      The CRc response category is comprised of the subset of participants who had abnormal cytogenetics at baseline and subsequently achieved CR during treatment in conjunction with a reversion to a normal karyotype. For the primary definition of CRc, a normal karyotype is defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques. Cytogenetic complete remission rate (CRc) 1) CR criteria met AND 2) Abnormal karyotype present at baseline AND 3) Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    4. Percentage of Participants With an Overall Response Rate (CR +CRi+ PR) [Overall response rate time frame was not analyzed.]

      Morphologic complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a one marrow aspirate with spicules and with at least 200 nucleated cells (there should be no blasts with auer rods) and ANC of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, no transfusions for 1 week prior to each assessment. No duration of these findings is required for confirmation of this response. Morphologic complete remission with incomplete blood count recovery was defined as a morphologic complete remission but the ANC may be < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L. Partial remission was defined as an ANC > 1 x 10^9/L and platelet count ≥ 100 x 10^9/L with a > 50% decrease in the percentage of bone marrow blasts to 5% to 25% (a blast count value of ≤ 5% may also be considered a partial remission if auer rods are present). Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    5. Progression-Free Survival (PFS) [Progression-Free survival data and time frame was not analyzed.]

      PFS is defined as the time from randomization to the first observation of documented disease progression or death from any cause whichever occurred first. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    6. Event-Free Survival (EFS) [Event-Free survival time was not analyzed.]

      EFS was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after CR or CRi, or death from any cause, whichever occurred first. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    7. Relapse-Free Survival (RFS) [Relapse-Free survival time frame was not analyzed.]

      RFS is defined only for subjects that achieve CR and CRi and is measured as the interval from that date to the date of disease relapse, death from any cause, whichever occurs first, censoring at the last visit date for subjects alive in continuous CR/CRi. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.

    8. Percentage of Participants With 30-Day Treatment-Related Mortality [30 days]

      30-day mortality rate was defined as death from any cause within 30 days after first dose.

    9. Number of Participants With Treatment Emergent Adverse Events (TEAE) [From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018]

      TEAEs were defined as those events that started on or after the first day of study drug up until 28 days after the last dose of study drug; Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; constitutes an important medical event. Severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); and according to the scale: Grade (Gr) 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death

    10. Number of Participants With a Second Primary Malignancy [From randomization of the last participant up to a minimum of 4 years following discontinuation]

      Second primary malignancies were monitored as events of interest and reported as serious adverse events regardless of the treatment arm the participant was enrolled in.

    Other Outcome Measures

    1. Percentage of Participants Alive at One Year [Up to 12 months]

      Defined as the percentage of participants who survived at one year

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Newly diagnosed acute myeloid leukemia (AML), AML with antecedent hematologic disorder or therapy-related AML

    • Male or female subjects aged ≥ 65

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

    • White blood cell (WBC) count ≤ 10 x 10⁹/L at screening

    Exclusion Criteria:

    • Previous treatment with azacitidine, decitabine, cytarabine or lenalidomide

    • Previous cytotoxic or biologic treatment of any kind for AML or prior use of targeted therapy agents.

    • Suspected or proven acute promyelocytic leukemia

    • Prior bone marrow or stem cell transplantation

    • Candidate for allogeneic bone marrow or stem cell transplantation

    • AML antecedent hematologic disorder such as chronic myelogenous leukemia or myeloproliferative neoplasms

    • Presence of malignant disease within the previous 12 months with exceptions

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 (210) University of Arizona Cancer Center Tucson Arizona United States 85724
    2 (180) University of California, San Diego La Jolla California United States 92093-0960
    3 (240) Cedars-Sinai Medical Center Los Angeles California United States 90048
    4 (215) Hematology Oncology Medical Group Orange California United States 92868
    5 (130) UC Davis Medical Center Sacramento California United States 95857
    6 (200) Coastal Integrative Cancer Care San Luis Obispo California United States 93401
    7 (125) University of Stanford Stanford California United States 94305
    8 (115) University of Colorado Anschultz Cancer Center Aurora Colorado United States 80045
    9 (145) Mount Sinai Comprehensive Cancer Center Miami Beach Florida United States 33140
    10 (140) Rush University Medical Center Chicago Illinois United States 60612
    11 (185) The University of Kansas Cancer Center Westwood Kansas United States 66205
    12 (175) University Lousiville Louisville Kentucky United States 40202
    13 (195) Tulane University Hospital Tulane Cancer Center New Orleans Louisiana United States 70072
    14 (235) University of Minnesota Minneapolis Minnesota United States 55455
    15 (100) Washington University School of Medicine Saint Louis Missouri United States 63110-1093
    16 (150) Billings Clinic Billings Montana United States 59101
    17 (165) Mount Sinai Medical Center New York New York New York United States 10029-65749
    18 (160) The Western Pennsylvania Hospital- Cancer Institute Pittsburgh Pennsylvania United States 15224-1791
    19 (205) Greenville Hospital System Greenville South Carolina United States 29605
    20 (120) Avera Cancer Institute Sioux Falls South Dakota United States 57105
    21 (230) Tennessee Oncology, PLLC Nashville Tennessee United States 37203
    22 (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center Dallas Texas United States 75390-9179
    23 (155) Cancer Care Centers of South Texas San Antonio Texas United States 78229
    24 (135) University of Wisconsin Madison Wisconsin United States 53792
    25 (402) Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    26 (405) University of Alberta Hospital Edmonton Alberta Canada T6G 1Z1
    27 (401) Cancer Care Manitoba Winnipeg Manitoba Canada R3E 0V9
    28 (403) Queen Elizabeth II Health Sciences Centre - VG Site Halifax Nova Scotia Canada B3H 2Y9
    29 (404) The Ottawa Hospital Ottawa Ontario Canada K1H 8L6
    30 (400) Princess Margaret Hospital Toronto Ontario Canada M5G 2M9

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Robert Gale, MD, Celgene

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01358734
    Other Study ID Numbers:
    • CC-5013-AML-001
    First Posted:
    May 24, 2011
    Last Update Posted:
    Jun 25, 2019
    Last Verified:
    Jun 1, 2019
    Keywords provided by Celgene
    AML
    elderly
    acute myelogenous leukemia
    vidaza
    azacitidine
    elderly AML
    revlimid
    lenalidomide
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Lenalidomide
    Azacitidine

    Study Results

    Participant Flow

    Recruitment Details Participants were randomized at 25 sites in North America (Canada and the United States).
    Pre-assignment Detail Participants were centrally randomized 1:1:1 and stratified by the Eastern Cooperative Oncology Group (ECOG) performance score (0 to 1 versus 2) and peripheral blood blast count (<1 versus ≥ 1 x 10^9/L).
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Period Title: Overall Study
    STARTED 15 39 34
    Safety Population 14 38 32
    COMPLETED 0 0 0
    NOT COMPLETED 15 39 34

    Baseline Characteristics

    Arm/Group Title Lenalidomide Azacitidine + Lenalidomide Azacitidine Total
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ daily SC on Days 1 through 7 and lenalidomide 50 mg daily PO on Days 8 through 28 followed by a 14-day rest period plus best supportive care Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC Total of all reporting groups
    Overall Participants 15 39 34 88
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    77.6
    (5.47)
    75.5
    (5.88)
    74.8
    (4.96)
    75.97
    (5.44)
    Sex: Female, Male (Count of Participants)
    Female
    3
    20%
    17
    43.6%
    15
    44.1%
    35
    39.8%
    Male
    12
    80%
    22
    56.4%
    19
    55.9%
    53
    60.2%
    Eastern Cooperative Oncology Group Performance Status (Count of Participants)
    0 = (Fully Active)
    4
    26.7%
    4
    10.3%
    10
    29.4%
    18
    20.5%
    1 = (Restrictive but ambulatory)
    9
    60%
    28
    71.8%
    17
    50%
    54
    61.4%
    (Ambulatory but unable to work)
    2
    13.3%
    7
    17.9%
    6
    17.6%
    15
    17%
    3 = (Limited self care)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4 = (Completely Disabled)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing
    0
    0%
    0
    0%
    1
    2.9%
    1
    1.1%
    Peripheral Blast Blood Count (Count of Participants)
    <1 X 10^9L
    11
    73.3%
    31
    79.5%
    27
    79.4%
    69
    78.4%
    ≥1 X 10^9L
    4
    26.7%
    8
    20.5%
    7
    20.6%
    19
    21.6%

    Outcome Measures

    1. Primary Outcome
    Title Kaplan Meier Estimates for One Year Survival
    Description One-year survival rate was defined as all deaths within one year from the date of randomization. All others censored at the at year 1 or date of discontinuation
    Time Frame Up to 24 months

    Outcome Measure Data

    Analysis Population Description
    ITT included all randomized participants
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 15 39 34
    Median (95% Confidence Interval) [months]
    3.00
    9.61
    13.67
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenalidomide, Azacitidine Plus Lenalidomide
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.119
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.789
    Confidence Interval (2-Sided) 95%
    0.861 to 3.718
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lenalidomide, Azacitidine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 2.659
    Confidence Interval (2-Sided) 95%
    1.214 to 5.822
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azacitidine Plus Lenalidomide, Azacitidine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.356
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.367
    Confidence Interval (2-Sided) 95%
    0.704 to 2.653
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
    Description Based on IWG response criteria for AML. Complete remission (CR), morphologic complete remission (CR) was defined as < 5% bone marrow blasts, an absolute neutrophil count ≥ 1 x 10^9/L, platelets ≥100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. Morphologic CR with incomplete blood count recovery (CRi) was defined as a morphologic complete remission but the ANC count may be <1 x 10^9/L and/or the platelet count may be <100 x 10^9/L. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Complete Response or Morphologic Incomplete Response data not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    3. Secondary Outcome
    Title Duration of Remission (DoR)
    Description Duration of remission was defined as the time from the date of CR or CRi until relapse. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Duration of Remission (DoR) time frame not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    4. Secondary Outcome
    Title Cytogenetic Complete Remission Rate (CRc)
    Description The CRc response category is comprised of the subset of participants who had abnormal cytogenetics at baseline and subsequently achieved CR during treatment in conjunction with a reversion to a normal karyotype. For the primary definition of CRc, a normal karyotype is defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques. Cytogenetic complete remission rate (CRc) 1) CR criteria met AND 2) Abnormal karyotype present at baseline AND 3) Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Cytogenetic Complete Remission timeframe was not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    5. Secondary Outcome
    Title Percentage of Participants With an Overall Response Rate (CR +CRi+ PR)
    Description Morphologic complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a one marrow aspirate with spicules and with at least 200 nucleated cells (there should be no blasts with auer rods) and ANC of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, no transfusions for 1 week prior to each assessment. No duration of these findings is required for confirmation of this response. Morphologic complete remission with incomplete blood count recovery was defined as a morphologic complete remission but the ANC may be < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L. Partial remission was defined as an ANC > 1 x 10^9/L and platelet count ≥ 100 x 10^9/L with a > 50% decrease in the percentage of bone marrow blasts to 5% to 25% (a blast count value of ≤ 5% may also be considered a partial remission if auer rods are present). Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Overall response rate time frame was not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    6. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS is defined as the time from randomization to the first observation of documented disease progression or death from any cause whichever occurred first. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Progression-Free survival data and time frame was not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    7. Secondary Outcome
    Title Event-Free Survival (EFS)
    Description EFS was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after CR or CRi, or death from any cause, whichever occurred first. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Event-Free survival time was not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    8. Secondary Outcome
    Title Relapse-Free Survival (RFS)
    Description RFS is defined only for subjects that achieve CR and CRi and is measured as the interval from that date to the date of disease relapse, death from any cause, whichever occurs first, censoring at the last visit date for subjects alive in continuous CR/CRi. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Time Frame Relapse-Free survival time frame was not analyzed.

    Outcome Measure Data

    Analysis Population Description
    Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 0 0 0
    9. Secondary Outcome
    Title Percentage of Participants With 30-Day Treatment-Related Mortality
    Description 30-day mortality rate was defined as death from any cause within 30 days after first dose.
    Time Frame 30 days

    Outcome Measure Data

    Analysis Population Description
    ITT included all randomized participants.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 15 39 34
    Number [percentage of participants]
    13.3
    88.7%
    17.9
    45.9%
    5.9
    17.4%
    10. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (TEAE)
    Description TEAEs were defined as those events that started on or after the first day of study drug up until 28 days after the last dose of study drug; Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; constitutes an important medical event. Severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); and according to the scale: Grade (Gr) 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
    Time Frame From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018

    Outcome Measure Data

    Analysis Population Description
    Safety population includes all participants who have received at least 1 dose of Investigational Product.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 14 38 32
    Any TEAE
    14
    93.3%
    38
    97.4%
    32
    94.1%
    ≥1 TEAE related to study drug
    13
    86.7%
    35
    89.7%
    30
    88.2%
    ≥1 TEAE CTCAE Grade 3 or 4 TEAE
    14
    93.3%
    34
    87.2%
    29
    85.3%
    ≥1 TEAE CTCAE Gr 3 or 4 TEAE related to study drug
    11
    73.3%
    25
    64.1%
    18
    52.9%
    ≥1 TEAE CTCAE Grade 5
    5
    33.3%
    10
    25.6%
    5
    14.7%
    ≥1 Serious TEAE
    13
    86.7%
    29
    74.4%
    25
    73.5%
    ≥1 Serious TEAE related to study drug
    10
    66.7%
    16
    41%
    7
    20.6%
    ≥1TEAE leading to discontinuation of study drug
    6
    40%
    12
    30.8%
    4
    11.8%
    ≥1TEAE leading to dose reduction of study drug
    0
    0%
    8
    20.5%
    2
    5.9%
    ≥1TEAE leading to dose interruption of study drug
    8
    53.3%
    21
    53.8%
    10
    29.4%
    11. Other Pre-specified Outcome
    Title Percentage of Participants Alive at One Year
    Description Defined as the percentage of participants who survived at one year
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who were randomized.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 15 39 34
    Number (95% Confidence Interval) [Percentage of participants]
    21.4
    142.7%
    43.9
    112.6%
    52.3
    153.8%
    12. Primary Outcome
    Title Overall Survival
    Description Overall Survival reported at the end of the study are for those participants who were alive at the end of the study
    Time Frame From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)

    Outcome Measure Data

    Analysis Population Description
    Participants who were still alive at the end of the study and in safety population.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 1 4 3
    Median (Full Range) [months]
    0.2
    7.1
    4.1
    13. Secondary Outcome
    Title Number of Participants With a Second Primary Malignancy
    Description Second primary malignancies were monitored as events of interest and reported as serious adverse events regardless of the treatment arm the participant was enrolled in.
    Time Frame From randomization of the last participant up to a minimum of 4 years following discontinuation

    Outcome Measure Data

    Analysis Population Description
    Safety population includes all participants who received at least one dose of IP
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    Measure Participants 14 38 32
    Number [Participants]
    0
    0%
    0
    0%
    3
    8.8%

    Adverse Events

    Time Frame From the date of randomization to 28 days after the last dose of study drug. Up to 15 May 2018.
    Adverse Event Reporting Description Between the date of first dose of IP up until and 28 days after the date of last dose of IP or that were present prior to the first day of IP but increased in severity or were assessed as related to IP during the study, including the follow-up 28-day time interval. All-cause mortality includes all deaths that occurred during the entire study.
    Arm/Group Title Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Arm/Group Description Participants received lenalidomide 50 mg daily (QD) by mouth (PO) for 28 days for the first 2 cycles followed by 25 mg QD PO for 28 days for the next 2 cycles followed by continuous 28-day cycles of oral lenalidomide 10 mg daily plus BSC, including antibiotics and transfusions, at the investigator's discretion. Participants received azacitidine 75 mg/m^2/ QD administered subcutaneously (SC) on Days 1 through 7 and lenalidomide 50 mg QD PO on days 8 through 28 followed by a 14-day rest period plus BSC Participants received azacitidine 75mg/m^2 administered SC on days 1 through 7 followed by a 21-day rest period plus BSC
    All Cause Mortality
    Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/14 (50%) 34/38 (89.5%) 29/32 (90.6%)
    Serious Adverse Events
    Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/14 (92.9%) 29/38 (76.3%) 25/32 (78.1%)
    Blood and lymphatic system disorders
    Febrile neutropenia 6/14 (42.9%) 16/38 (42.1%) 8/32 (25%)
    Anaemia 2/14 (14.3%) 2/38 (5.3%) 2/32 (6.3%)
    Thrombocytopenia 2/14 (14.3%) 2/38 (5.3%) 1/32 (3.1%)
    Disseminated intravascular coagulation 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Leukocytosis 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Heparin-induced thrombocytopenia 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Neutropenia 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Pancytopenia 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Cardiac disorders
    Atrial fibrillation 1/14 (7.1%) 3/38 (7.9%) 1/32 (3.1%)
    Angina pectoris 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Angina unstable 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Atrial flutter 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Cardiac arrest 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Cardiac failure 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Cardiac failure congestive 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Cardio-respiratory arrest 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Ear and labyrinth disorders
    Middle ear inflammation 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 0/14 (0%) 2/38 (5.3%) 1/32 (3.1%)
    Constipation 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Diarrhoea 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Small intestinal haemorrhage 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    General disorders
    Fatigue 2/14 (14.3%) 0/38 (0%) 1/32 (3.1%)
    Non-cardiac chest pain 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Pyrexia 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Asthenia 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Malaise 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Oedema peripheral 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Performance status decreased 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Systemic inflammatory response syndrome 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Infections and infestations
    Pneumonia 3/14 (21.4%) 4/38 (10.5%) 7/32 (21.9%)
    Sepsis 2/14 (14.3%) 1/38 (2.6%) 2/32 (6.3%)
    Cellulitis 0/14 (0%) 3/38 (7.9%) 1/32 (3.1%)
    Septic shock 2/14 (14.3%) 1/38 (2.6%) 0/32 (0%)
    Bronchopulmonary aspergillosis 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Clostridium difficile colitis 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Klebsiella bacteraemia 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Subcutaneous abscess 0/14 (0%) 1/38 (2.6%) 1/32 (3.1%)
    Breast abscess 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Clostridium difficile infection 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Enterobacter bacteraemia 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Herpes zoster 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Klebsiella sepsis 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Lobar pneumonia 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Lung infection 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Osteomyelitis 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Pneumonia fungal 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Pneumonia staphylococcal 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Postoperative wound infection 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Pseudomonas infection 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Scrotal abscess 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Soft tissue infection 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Urinary tract infection 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Urinary tract infection enterococcal 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Viral upper respiratory tract infection 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Injury, poisoning and procedural complications
    Fall 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Femoral neck fracture 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Femur fracture 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Head injury 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Subdural haemorrhage 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Investigations
    Blast cell count increased 0/14 (0%) 1/38 (2.6%) 1/32 (3.1%)
    Blood bilirubin increased 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Bone marrow myelogram abnormal 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Megakaryocytes decreased 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Decreased appetite 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Fluid overload 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Hyponatraemia 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Tumour lysis syndrome 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Failure to thrive 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Hyperglycaemia 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Hypoglycaemia 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Arthritis 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Back pain 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Haemarthrosis 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Osteoarthritis 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer metastatic 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Leukaemic infiltration extramedullary 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Squamous cell carcinoma of skin 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Vulval cancer stage 0 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Nervous system disorders
    Syncope 1/14 (7.1%) 0/38 (0%) 2/32 (6.3%)
    Central nervous system lesion 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Cerebrovascular accident 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Depressed level of consciousness 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Haemorrhage intracranial 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Status epilepticus 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Subarachnoid haemorrhage 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Transient ischaemic attack 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Renal and urinary disorders
    Renal failure acute 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Renal failure 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Urinary retention 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Pulmonary haemorrhage 2/14 (14.3%) 1/38 (2.6%) 0/32 (0%)
    Acute respiratory distress syndrome 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Acute respiratory failure 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Epistaxis 0/14 (0%) 1/38 (2.6%) 1/32 (3.1%)
    Hypoxia 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Pleural effusion 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Pulmonary embolism 0/14 (0%) 1/38 (2.6%) 1/32 (3.1%)
    Pulmonary infarction 2/14 (14.3%) 0/38 (0%) 0/32 (0%)
    Chronic obstructive pulmonary disease 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Interstitial lung disease 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Pulmonary oedema 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Respiratory failure 0/14 (0%) 0/38 (0%) 1/32 (3.1%)
    Skin and subcutaneous tissue disorders
    Angioedema 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Erythema multiforme 0/14 (0%) 1/38 (2.6%) 0/32 (0%)
    Rash maculo-papular 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Vascular disorders
    Deep vein thrombosis 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Hypotension 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Orthostatic hypotension 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Other (Not Including Serious) Adverse Events
    Lenalidomide Azacitidine Plus Lenalidomide Azacitidine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/14 (100%) 38/38 (100%) 32/32 (100%)
    Blood and lymphatic system disorders
    Anaemia 6/14 (42.9%) 11/38 (28.9%) 10/32 (31.3%)
    Thrombocytopenia 3/14 (21.4%) 11/38 (28.9%) 11/32 (34.4%)
    Neutropenia 4/14 (28.6%) 6/38 (15.8%) 9/32 (28.1%)
    Febrile neutropenia 0/14 (0%) 6/38 (15.8%) 2/32 (6.3%)
    Pancytopenia 2/14 (14.3%) 2/38 (5.3%) 1/32 (3.1%)
    Leukocytosis 2/14 (14.3%) 1/38 (2.6%) 1/32 (3.1%)
    Leukopenia 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Autoimmune haemolytic anaemia 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Spleen disorder 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Splenic lesion 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Cardiac disorders
    Atrial fibrillation 2/14 (14.3%) 5/38 (13.2%) 1/32 (3.1%)
    Tachycardia 1/14 (7.1%) 2/38 (5.3%) 5/32 (15.6%)
    Angina pectoris 1/14 (7.1%) 2/38 (5.3%) 1/32 (3.1%)
    Bradycardia 0/14 (0%) 4/38 (10.5%) 0/32 (0%)
    Sinus tachycardia 0/14 (0%) 2/38 (5.3%) 2/32 (6.3%)
    Atrial flutter 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Cardiac failure congestive 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Cardiac disorder 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Supraventricular tachycardia 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Ear and labyrinth disorders
    Ear congestion 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Ear discomfort 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Hypoacusis 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Eye disorders
    Vision blurred 2/14 (14.3%) 2/38 (5.3%) 1/32 (3.1%)
    Erythema of eyelid 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Eye inflammation 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Lacrimation increased 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Gastrointestinal disorders
    Constipation 7/14 (50%) 24/38 (63.2%) 17/32 (53.1%)
    Nausea 4/14 (28.6%) 19/38 (50%) 22/32 (68.8%)
    Diarrhoea 5/14 (35.7%) 19/38 (50%) 8/32 (25%)
    Vomiting 3/14 (21.4%) 7/38 (18.4%) 12/32 (37.5%)
    Abdominal pain 1/14 (7.1%) 5/38 (13.2%) 6/32 (18.8%)
    Oral disorder 3/14 (21.4%) 3/38 (7.9%) 1/32 (3.1%)
    Stomatitis 0/14 (0%) 4/38 (10.5%) 3/32 (9.4%)
    Dysphagia 0/14 (0%) 5/38 (13.2%) 1/32 (3.1%)
    Haemorrhoids 0/14 (0%) 2/38 (5.3%) 3/32 (9.4%)
    Dry mouth 0/14 (0%) 3/38 (7.9%) 1/32 (3.1%)
    Dyspepsia 0/14 (0%) 2/38 (5.3%) 2/32 (6.3%)
    Gastrooesophageal reflux disease 2/14 (14.3%) 1/38 (2.6%) 1/32 (3.1%)
    Oral pain 1/14 (7.1%) 2/38 (5.3%) 1/32 (3.1%)
    Abdominal distension 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Mouth haemorrhage 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Rectal haemorrhage 0/14 (0%) 1/38 (2.6%) 2/32 (6.3%)
    Tongue ulceration 1/14 (7.1%) 2/38 (5.3%) 0/32 (0%)
    Toothache 1/14 (7.1%) 2/38 (5.3%) 0/32 (0%)
    Faeces discoloured 2/14 (14.3%) 0/38 (0%) 0/32 (0%)
    Flatulence 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Gingival bleeding 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Abdominal tenderness 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Gastrointestinal haemorrhage 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Odynophagia 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Tongue coated 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    General disorders
    Fatigue 8/14 (57.1%) 15/38 (39.5%) 14/32 (43.8%)
    Oedema peripheral 6/14 (42.9%) 7/38 (18.4%) 7/32 (21.9%)
    Pyrexia 3/14 (21.4%) 9/38 (23.7%) 8/32 (25%)
    Asthenia 4/14 (28.6%) 7/38 (18.4%) 3/32 (9.4%)
    Chills 3/14 (21.4%) 5/38 (13.2%) 2/32 (6.3%)
    Injection site erythema 0/14 (0%) 4/38 (10.5%) 6/32 (18.8%)
    Injection site reaction 0/14 (0%) 3/38 (7.9%) 6/32 (18.8%)
    Injection site pain 0/14 (0%) 7/38 (18.4%) 1/32 (3.1%)
    Pain 0/14 (0%) 4/38 (10.5%) 3/32 (9.4%)
    Mucosal inflammation 1/14 (7.1%) 4/38 (10.5%) 1/32 (3.1%)
    Device occlusion 1/14 (7.1%) 1/38 (2.6%) 2/32 (6.3%)
    Injection site bruising 0/14 (0%) 1/38 (2.6%) 3/32 (9.4%)
    Injection site irritation 0/14 (0%) 2/38 (5.3%) 2/32 (6.3%)
    Non-cardiac chest pain 1/14 (7.1%) 1/38 (2.6%) 2/32 (6.3%)
    Catheter site pain 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Face oedema 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Facial pain 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Gait disturbance 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Generalised oedema 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Injection site discomfort 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Localised oedema 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Malaise 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Mucosal haemorrhage 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Oedema 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Feeling abnormal 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Local swelling 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/14 (7.1%) 2/38 (5.3%) 0/32 (0%)
    Infections and infestations
    Pneumonia 3/14 (21.4%) 4/38 (10.5%) 4/32 (12.5%)
    Cellulitis 1/14 (7.1%) 5/38 (13.2%) 4/32 (12.5%)
    Urinary tract infection 1/14 (7.1%) 3/38 (7.9%) 6/32 (18.8%)
    Upper respiratory tract infection 0/14 (0%) 6/38 (15.8%) 3/32 (9.4%)
    Herpes simplex 2/14 (14.3%) 4/38 (10.5%) 1/32 (3.1%)
    Oral candidiasis 2/14 (14.3%) 2/38 (5.3%) 3/32 (9.4%)
    Herpes zoster 1/14 (7.1%) 0/38 (0%) 3/32 (9.4%)
    Nasopharyngitis 0/14 (0%) 2/38 (5.3%) 2/32 (6.3%)
    Respiratory tract infection 0/14 (0%) 4/38 (10.5%) 0/32 (0%)
    Sinusitis 0/14 (0%) 3/38 (7.9%) 1/32 (3.1%)
    Fungal infection 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Furuncle 0/14 (0%) 3/38 (7.9%) 0/32 (0%)
    Hordeolum 0/14 (0%) 2/38 (5.3%) 1/32 (3.1%)
    Oral herpes 0/14 (0%) 1/38 (2.6%) 2/32 (6.3%)
    Rash pustular 1/14 (7.1%) 2/38 (5.3%) 0/32 (0%)
    Tooth abscess 0/14 (0%) 1/38 (2.6%) 2/32 (6.3%)
    Clostridium difficile colitis 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Ear infection 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Mucosal infection 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Osteomyelitis 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Tooth infection 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Body tinea 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Injury, poisoning and procedural complications
    Contusion 1/14 (7.1%) 5/38 (13.2%) 6/32 (18.8%)
    Fall 1/14 (7.1%) 3/38 (7.9%) 1/32 (3.1%)
    Procedural pain 1/14 (7.1%) 1/38 (2.6%) 2/32 (6.3%)
    Scratch 0/14 (0%) 1/38 (2.6%) 2/32 (6.3%)
    Transfusion reaction 1/14 (7.1%) 0/38 (0%) 2/32 (6.3%)
    Wound 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Cartilage injury 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Ligament sprain 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Muscle injury 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Muscle rupture 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Upper limb fracture 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Investigations
    Weight decreased 5/14 (35.7%) 15/38 (39.5%) 10/32 (31.3%)
    Neutrophil count decreased 0/14 (0%) 5/38 (13.2%) 4/32 (12.5%)
    White blood cell count decreased 0/14 (0%) 4/38 (10.5%) 5/32 (15.6%)
    Platelet count decreased 0/14 (0%) 6/38 (15.8%) 2/32 (6.3%)
    Alanine aminotransferase increased 1/14 (7.1%) 5/38 (13.2%) 0/32 (0%)
    Aspartate aminotransferase increased 0/14 (0%) 5/38 (13.2%) 1/32 (3.1%)
    Blood magnesium decreased 1/14 (7.1%) 4/38 (10.5%) 0/32 (0%)
    Blood creatinine increased 1/14 (7.1%) 2/38 (5.3%) 1/32 (3.1%)
    Cardiac murmur 3/14 (21.4%) 1/38 (2.6%) 0/32 (0%)
    International normalised ratio increased 1/14 (7.1%) 3/38 (7.9%) 0/32 (0%)
    Lymphocyte count decreased 1/14 (7.1%) 2/38 (5.3%) 1/32 (3.1%)
    Blood bilirubin increased 0/14 (0%) 2/38 (5.3%) 1/32 (3.1%)
    Transaminases increased 2/14 (14.3%) 1/38 (2.6%) 0/32 (0%)
    Weight increased 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Blood alkaline phosphatase increased 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Oxygen saturation decreased 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Staphylococcus test positive 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Vitamin D decreased 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Activated partial thromboplastin time abnormal 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Clostridium test positive 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Electrocardiogram QT prolonged 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 4/14 (28.6%) 18/38 (47.4%) 10/32 (31.3%)
    Hypokalaemia 7/14 (50%) 12/38 (31.6%) 8/32 (25%)
    Hypomagnesaemia 0/14 (0%) 8/38 (21.1%) 2/32 (6.3%)
    Hyponatraemia 2/14 (14.3%) 5/38 (13.2%) 2/32 (6.3%)
    Hypocalcaemia 2/14 (14.3%) 2/38 (5.3%) 4/32 (12.5%)
    Hypoalbuminaemia 4/14 (28.6%) 3/38 (7.9%) 0/32 (0%)
    Dehydration 1/14 (7.1%) 1/38 (2.6%) 4/32 (12.5%)
    Hypophosphataemia 0/14 (0%) 5/38 (13.2%) 1/32 (3.1%)
    Hyperglycaemia 2/14 (14.3%) 2/38 (5.3%) 1/32 (3.1%)
    Fluid overload 0/14 (0%) 3/38 (7.9%) 0/32 (0%)
    Hypoglycaemia 0/14 (0%) 1/38 (2.6%) 2/32 (6.3%)
    Hypovolaemia 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Failure to thrive 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Glucose tolerance impaired 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Hyperphosphataemia 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Hyperuricaemia 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Vitamin K deficiency 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/14 (21.4%) 8/38 (21.1%) 11/32 (34.4%)
    Back pain 1/14 (7.1%) 3/38 (7.9%) 9/32 (28.1%)
    Pain in extremity 1/14 (7.1%) 7/38 (18.4%) 3/32 (9.4%)
    Muscular weakness 1/14 (7.1%) 7/38 (18.4%) 0/32 (0%)
    Muscle spasms 1/14 (7.1%) 3/38 (7.9%) 2/32 (6.3%)
    Neck pain 0/14 (0%) 2/38 (5.3%) 4/32 (12.5%)
    Arthritis 1/14 (7.1%) 3/38 (7.9%) 0/32 (0%)
    Musculoskeletal pain 0/14 (0%) 1/38 (2.6%) 3/32 (9.4%)
    Myalgia 0/14 (0%) 3/38 (7.9%) 1/32 (3.1%)
    Joint swelling 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Arthropathy 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Bursitis 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Osteoarthritis 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal neoplasm 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Nervous system disorders
    Dizziness 3/14 (21.4%) 12/38 (31.6%) 6/32 (18.8%)
    Headache 1/14 (7.1%) 9/38 (23.7%) 4/32 (12.5%)
    Dysgeusia 1/14 (7.1%) 6/38 (15.8%) 3/32 (9.4%)
    Syncope 2/14 (14.3%) 2/38 (5.3%) 3/32 (9.4%)
    Tremor 0/14 (0%) 4/38 (10.5%) 0/32 (0%)
    Neuropathy peripheral 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Balance disorder 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Hypoaesthesia 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Paraesthesia 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Presyncope 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Psychiatric disorders
    Insomnia 4/14 (28.6%) 8/38 (21.1%) 2/32 (6.3%)
    Anxiety 0/14 (0%) 10/38 (26.3%) 3/32 (9.4%)
    Depression 1/14 (7.1%) 4/38 (10.5%) 4/32 (12.5%)
    Confusional state 1/14 (7.1%) 4/38 (10.5%) 2/32 (6.3%)
    Agitation 1/14 (7.1%) 2/38 (5.3%) 2/32 (6.3%)
    Mental status changes 1/14 (7.1%) 2/38 (5.3%) 2/32 (6.3%)
    Delirium 0/14 (0%) 3/38 (7.9%) 0/32 (0%)
    Renal and urinary disorders
    Dysuria 0/14 (0%) 3/38 (7.9%) 4/32 (12.5%)
    Haematuria 0/14 (0%) 5/38 (13.2%) 0/32 (0%)
    Renal failure acute 0/14 (0%) 2/38 (5.3%) 2/32 (6.3%)
    Urinary retention 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Pollakiuria 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Renal cyst 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Renal failure 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Azotaemia 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Renal disorder 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Renal tubular necrosis 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/14 (35.7%) 12/38 (31.6%) 8/32 (25%)
    Dyspnoea 3/14 (21.4%) 16/38 (42.1%) 4/32 (12.5%)
    Epistaxis 2/14 (14.3%) 6/38 (15.8%) 6/32 (18.8%)
    Oropharyngeal pain 1/14 (7.1%) 7/38 (18.4%) 2/32 (6.3%)
    Pleural effusion 1/14 (7.1%) 2/38 (5.3%) 5/32 (15.6%)
    Productive cough 0/14 (0%) 3/38 (7.9%) 3/32 (9.4%)
    Rhinorrhoea 1/14 (7.1%) 4/38 (10.5%) 1/32 (3.1%)
    Haemoptysis 1/14 (7.1%) 2/38 (5.3%) 2/32 (6.3%)
    Hypoxia 1/14 (7.1%) 4/38 (10.5%) 0/32 (0%)
    Pulmonary oedema 1/14 (7.1%) 4/38 (10.5%) 0/32 (0%)
    Chronic obstructive pulmonary disease 0/14 (0%) 3/38 (7.9%) 1/32 (3.1%)
    Dyspnoea exertional 0/14 (0%) 1/38 (2.6%) 3/32 (9.4%)
    Acute respiratory failure 0/14 (0%) 3/38 (7.9%) 0/32 (0%)
    Dysphonia 0/14 (0%) 3/38 (7.9%) 0/32 (0%)
    Pleuritic pain 1/14 (7.1%) 2/38 (5.3%) 0/32 (0%)
    Pulmonary mass 0/14 (0%) 2/38 (5.3%) 1/32 (3.1%)
    Tachypnoea 1/14 (7.1%) 0/38 (0%) 2/32 (6.3%)
    Wheezing 0/14 (0%) 2/38 (5.3%) 1/32 (3.1%)
    Laryngeal inflammation 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Lung infiltration 2/14 (14.3%) 0/38 (0%) 0/32 (0%)
    Pneumonitis 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Rales 2/14 (14.3%) 0/38 (0%) 0/32 (0%)
    Sinus congestion 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Lung disorder 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Pulmonary hypertension 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Respiratory distress 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus 3/14 (21.4%) 14/38 (36.8%) 2/32 (6.3%)
    Rash 3/14 (21.4%) 10/38 (26.3%) 6/32 (18.8%)
    Erythema 0/14 (0%) 7/38 (18.4%) 2/32 (6.3%)
    Petechiae 3/14 (21.4%) 4/38 (10.5%) 1/32 (3.1%)
    Rash generalised 2/14 (14.3%) 4/38 (10.5%) 2/32 (6.3%)
    Rash maculo-papular 0/14 (0%) 4/38 (10.5%) 2/32 (6.3%)
    Night sweats 0/14 (0%) 3/38 (7.9%) 1/32 (3.1%)
    Decubitus ulcer 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Hyperhidrosis 1/14 (7.1%) 1/38 (2.6%) 1/32 (3.1%)
    Pruritus generalised 0/14 (0%) 2/38 (5.3%) 1/32 (3.1%)
    Rash erythematous 1/14 (7.1%) 2/38 (5.3%) 0/32 (0%)
    Blister 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Ecchymosis 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Rash macular 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Skin discolouration 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Skin exfoliation 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Skin lesion 0/14 (0%) 0/38 (0%) 2/32 (6.3%)
    Skin ulcer 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Urticaria 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Dermal cyst 1/14 (7.1%) 0/38 (0%) 0/32 (0%)
    Vascular disorders
    Hypotension 4/14 (28.6%) 6/38 (15.8%) 1/32 (3.1%)
    Hypertension 1/14 (7.1%) 3/38 (7.9%) 2/32 (6.3%)
    Deep vein thrombosis 1/14 (7.1%) 1/38 (2.6%) 2/32 (6.3%)
    Orthostatic hypotension 0/14 (0%) 2/38 (5.3%) 0/32 (0%)
    Thrombophlebitis superficial 1/14 (7.1%) 0/38 (0%) 1/32 (3.1%)
    Venous thrombosis limb 1/14 (7.1%) 1/38 (2.6%) 0/32 (0%)
    Phlebitis 1/14 (7.1%) 0/38 (0%) 0/32 (0%)

    Limitations/Caveats

    Accrual to the lenalidomide arm was stopped before ending accrual to the 2 other arms because of poor tolerability and no comparison of outcomes was planned.

    More Information

    Certain Agreements

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

    Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications

    Results Point of Contact

    Name/Title Anne McClain, Senior Manager, Clinical Trial Disclosure
    Organization Celgene Corporation
    Phone 888-260-1599
    Email ClinicalTrialDisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01358734
    Other Study ID Numbers:
    • CC-5013-AML-001
    First Posted:
    May 24, 2011
    Last Update Posted:
    Jun 25, 2019
    Last Verified:
    Jun 1, 2019