Lenalidomide Safety/Efficacy in Myelodysplastic Syndromes (MDS) Associated With a Deletion (Del)(5q) Cytogenetic Abnormality

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT00065156
Collaborator
(none)
148
Enrollment
32
Locations
1
Arm
62
Actual Duration (Months)
4.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a multicenter, single-arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion-dependent subjects with low- or intermediate-1-risk Myelodysplastic Syndromes (MDS) associated with a del (5q31-33) cytogenetic abnormality. Screening procedures will take place within 28 days of the first day of lenalidomide treatment. Subjects will receive lenalidomide in 28-day cycles for up to 6 cycles, or until bone marrow disease progression or progression/relapse following erythroid hematologic improvement is documented. Study visits will occur every cycle (every 28 days) and laboratory monitoring to assess hematological parameters will occur every 14 days. Safety and efficacy assessments to be performed during the study are outlined in the Schedule of Study Assessments.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
148 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of Lenalidomide Monotherapy in Red Blood Cell Transfusion-dependent Subjects With Myelodysplastic Syndromes Associated With a Del(5q) Cytogenetic Abnormality.
Actual Study Start Date :
Jun 1, 2003
Actual Primary Completion Date :
Aug 1, 2008
Actual Study Completion Date :
Aug 1, 2008

Arms and Interventions

ArmIntervention/Treatment
Experimental: Lenalidomide

Drug: lenalidomide
10 mg orally once daily for 21 days out of a 28-day cycle (syncopated); subsequently amended (Amendment 1, dated 27 August 2003) to employ a continuous dosage regimen in which 10 mg was taken once daily for 28 day cycles (continuous). Subjects who initially began a syncopated regimen and who did not experience a dose-limiting adverse event were allowed to switch to the continuous regimen.
Other Names:
  • CC-5013
  • Outcome Measures

    Primary Outcome Measures

    1. Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence [Up to 2 years]

      Number of participants who achieved RBC-transfusion independence, which was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (eg, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin.

    Secondary Outcome Measures

    1. Participants With Adverse Experiences [Up to 2 Years]

      Counts of study participants who had adverse events (AEs) during the study. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator. The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE.

    2. Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study [Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)]

      A participant was categorized as having a transfusion reduction response if there was a ≥ 50% decrease from pretreatment transfusion requirements (before the start of the study mediation) compared to any consecutive 56 days during the study (i.e. post treatment).

    3. Time to Transfusion Independence [up to 2 years]

      Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Time to transfusion independence was defined as the day of the first dose of study drug to the first day of the first 56-day RBC transfusion-free period.

    4. Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study [up to 2 years]

      Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Participants who relapsed required a transfusion after the period of transfusion independence. Participants who maintained transfusion independence did not require a transfusion during the remainder of the study.

    5. Kaplan Meier Estimate for Duration of Transfusion Independence Response [up to 2 years]

      Duration of response is measured from the first of the consecutive 56 days during which the participant was free of RBC transfusions to the date of the first RBC transfusion after this period. Duration of response was censored at the date of last visit for participants who maintained transfusion independence.

    6. Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders [Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)]

      The change from baseline in hemoglobin for participants who became RBC-transfusion independent. The maximum hemoglobin value obtained during the response period is used in the calculation of change from baseline.

    7. Participant Counts of Cytogenetic Response [up to 2 years]

      Participants deemed evaluable by the central cytogenetic review had their cytogenetic response categorized as major or minor. A major cytogenetic response was defined as ≥ 20 metaphases recorded at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with no abnormal metaphases observed. A minor cytogenetic response was defined as ≥ 20 metaphases analyzed at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with a ≥ 50% reduction in the proportion of hematopoietic cells with cytogenetic abnormalities compared with baseline.

    8. Participant Counts of Platelet Response [up to 2 years]

      Major platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3 in all values within 56 days of start of treatment, an absolute increase of ≥30,000/mm^3 sustained for ≥56 consecutive days. In platelet transfusion-dependent participants, a major response was stabilization of platelet counts and platelet transfusion independence. Minor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3, a ≥ 50% increase in platelet count with a net increase >10,000/mm^3 for a consecutive 56-day period in the absence of platelet transfusions.

    9. Participant Counts of Absolute Neutrophil Count (ANC) Response [up to 2 years]

      Major neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3 in all values obtained within 56 days of start of treatment, a ≥ 100% increase or an absolute increase of ≥ 500/mm^3, whichever was greater (at least to be ≥ 500/mm^3), sustained for 56 consecutive days. Minor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3, an increase in ANC concentration of ≥ 100% sustained for 56 consecutive days.

    10. Participants With Complete or Partial Bone Marrow Improvement [up to 2 years]

      Bone marrow aspirates were assessed by a central reviewer. A complete bone marrow improvement required a baseline French-American-British (FAB) classification (see Baseline Characteristics) of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) and a during study assessment of no MDS. A partial bone marrow improvement reflected an improved FAB classification compared to baseline (e.g. RARS to RA) but evidence of MDS continued to exist.

    11. Participants With Bone Marrow Progression [up to 2 years]

      Bone marrow aspirate was assessed by a central reviewer. Progression is represented in two categories according to changes from baseline in French-American-British (FAB) classification (see Baseline Characteristics): Baseline classification of refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) to a during treatment (plus 30 days) classification of refractory anemia with excess blasts (RAEB). Any baseline FAB classification to a during treatment (plus 30 days) classification of acute myeloid leukemia (AML).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Must understand and voluntarily sign an informed consent form

    • Age 18 years or older at the time of signing the informed consent

    • Must be able to adhere to the study visit schedule and other protocol requirements.

    • Diagnosis of low or intermediate-1-risk International Prognostic Scoring System (IPSS) Myelodysplastic Syndromes (MDS) without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.

    • Red blood cell (RBC) transfusion-dependent anemia defined as having received greater than or equal to 2 units of RBCs within 8 weeks of the first day of study drug treatment.

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

    • Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug.

    • Sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.

    • WCBP must agree to have pregnancy tests every 4 weeks while on study drug.

    Exclusion Criteria:
    • Pregnant or lactating females

    • Prior therapy with lenalidomide.

    • An abnormality of chromosome 5 involving a deletion between bands q31 and q33.

    • Lab Abnormality: Absolute neutrophil count (ANC) <500 cell/mm3 (0.5*109/L)

    • Lab Abnormality: Platelet count <50,000/mm3 (50*109/L)

    • Lab Abnormality: Serum creatinine >2.5 mg/dL (221 mmol/L)

    • Lab Abnormality: Serum total bilirubin >2.0 mg/dL (34 mmol/L)

    • Prior greater than or equal to grade 3 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) allergic reaction/hypersensitivity to thalidomide.

    • Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding

    • If a marrow aspirate is not evaluable for storage iron, transferrin saturation must be

    20% and serum ferritin not less than 50 ng/mL

    • Use of hematopoietic growth factors within 7 days of the first day of study drug treatment.

    • Prior greater than or equal to grade 3 NCI CTC rash or any desquamation (blistering) while taking thalidomide.

    • Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to >10 mg/day of prednisone) within 28 days of the first day of study drug treatment.

    • Use of experimental or standard drugs (i.e. chemotherapeutic, immunosuppressive, and cytoprotective agents) for the treatment of MDS within 28 days of the first day of study drug treatment.

    • Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for greater than or equal to 3 years.

    • Use of any other experimental therapy within 28 days of the first day of study drug treatment.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Arizona Cancer CenterScottsdaleArizonaUnited States85258
    2Mayo ClinicScottsdaleArizonaUnited States85259
    3Arizona Cancer CenterTucsonArizonaUnited States85724-5024
    4Desert Hematology & Oncology Medical GroupRancho MirageCaliforniaUnited States92270
    5Stanford University Medical CenterStanfordCaliforniaUnited States94305-5750
    6Mayo ClinicJacksonvilleFloridaUnited States32224
    7Cancer & Blood Disease CenterLecantoFloridaUnited States34461
    8University of Miami Sylvester Comp Cancer CenterMiamiFloridaUnited States33136
    9H. Lee Moffitt Cancer Center and Research InstituteTampaFloridaUnited States33612-9497
    10Northwest Georgia Oncology - Wellstar Cancer ResearchMariettaGeorgiaUnited States30060
    11Rush-Presbyterian- St. Luke's Medical CenterChicagoIllinoisUnited States60612
    12University of Chicago Medical CenterChicagoIllinoisUnited States60637-1470
    13Midwest Cancer Research GroupSkokieIllinoisUnited States60077
    14Johns Hopkins Oncology CenterBaltimoreMarylandUnited States21287-8963
    15Dana-Farber Cancer InstituteBostonMassachusettsUnited States02115-6084
    16Wayne State University School of MedicineDetroitMichiganUnited States48201-2097
    17Mayo ClinicRochesterMinnesotaUnited States55905
    18University of Nebraska Medical CenterOmahaNebraskaUnited States68198-7680
    19Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263
    20New York Hospital-CornellNew YorkNew YorkUnited States10021-0034
    21Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10021-6007
    22Mt. Sinai Medical CenterNew YorkNew YorkUnited States10029
    23University of Rochester- James P. Wilmot Cancer CenterRochesterNew YorkUnited States14642
    24Wake Forest University School of MedicineWinston-SalemNorth CarolinaUnited States27157-1082
    25The Cleveland Clinic FoundationClevelandOhioUnited States44195
    26Oregon Health & Science UniversityPortlandOregonUnited States97201
    27Kaiser Permanente Northwest RegionPortlandOregonUnited States97227
    28Western Pennsylvania Cancer InstitutePittsburghPennsylvaniaUnited States15224
    29MD Anderson Cancer CenterHoustonTexasUnited States77030
    30Swedish Cancer InstituteSeattleWashingtonUnited States98104
    31Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98109-4417
    32St. Johannes HospitalDuisburgGermany

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Principal Investigator: Alan F List, MD, H. Lee Moffitt Cancer Center and Research Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00065156
    Other Study ID Numbers:
    • CC-5013-MDS-003
    • NCT00074126
    First Posted:
    Jul 18, 2003
    Last Update Posted:
    Nov 19, 2019
    Last Verified:
    Nov 1, 2019

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Period Title: Overall Study
    STARTED148
    Modified Intent to Treat Population94
    COMPLETED24
    NOT COMPLETED124

    Baseline Characteristics

    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Overall Participants148
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.0
    (10.50)
    Age, Customized (participants) [Number]
    <= 65 years
    48
    32.4%
    >65 years
    100
    67.6%
    Sex: Female, Male (Count of Participants)
    Female
    97
    65.5%
    Male
    51
    34.5%
    Race/Ethnicity, Customized (participants) [Number]
    White
    143
    96.6%
    Hispanic
    3
    2%
    Asian/Pacific Islander
    2
    1.4%
    Region of Enrollment (participants) [Number]
    United States
    112
    75.7%
    Germany
    36
    24.3%
    Duration of Myelodysplastic Syndrome (MDS) (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    3.4
    (3.29)
    Participants with 5q(-) (31-33) Chromosomal Abnormality (participants) [Number]
    Number [participants]
    148
    100%
    International Prognostic Scoring System (IPSS) Score (participants) [Number]
    Low (0)
    49
    33.1%
    Intermediate-1 (0.5 to 1.0)
    69
    46.6%
    Intermediate-2 (1.5 to 2.0)
    7
    4.7%
    High (>=2.5)
    2
    1.4%
    Missing (unable to assign)
    21
    14.2%
    French-American-British (FAB) Classification (participants) [Number]
    Refractory anemia (RA)
    78
    52.7%
    Refractory anemia with ringed sideroblasts (RARS)
    16
    10.8%
    Refractory anemia with excess blasts (RAEB)
    30
    20.3%
    Chronic myelomonocytic leukemia (CMML)
    3
    2%
    Acute leukemia
    1
    0.7%
    Unable to classify
    20
    13.5%
    Cytogenetic Complexity (participants) [Number]
    Isolated 5q
    110
    74.3%
    Intermediate (5q + 1 abnormality)
    25
    16.9%
    Complex
    12
    8.1%
    Unknown
    1
    0.7%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
    0
    59
    39.9%
    1
    75
    50.7%
    2
    14
    9.5%
    3 - 5
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleParticipants Who Achieved Red Blood Cell (RBC) -Transfusion Independence
    DescriptionNumber of participants who achieved RBC-transfusion independence, which was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (eg, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (MITT) diagnosis of low- or int-1-risk MDS associated with a del(5q) cytogenetic abnormality based on central hematologic and cytogenetic reviewers confirmation received ≥2 transfusions in each of the 8-week periods during the 16 week pre-treatment period received ≥1 dose of study drug
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants94
    Number [participants]
    59
    39.9%
    2. Secondary Outcome
    TitleParticipants With Adverse Experiences
    DescriptionCounts of study participants who had adverse events (AEs) during the study. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator. The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE.
    Time FrameUp to 2 Years

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least one dose of study drug.
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants148
    At least one AE
    148
    100%
    At least one AE related to study drug
    143
    96.6%
    At least one NCI CTC grade 3-4 AE
    140
    94.6%
    At least one NCI CTC grade 3-4 AE related to drug
    131
    88.5%
    At least one serious AE
    89
    60.1%
    At least one serious AE related to study drug
    40
    27%
    AE leading to dose reduction or interruption
    131
    88.5%
    AE leading to discontinuation of study drug
    47
    31.8%
    3. Secondary Outcome
    TitleParticipants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study
    DescriptionA participant was categorized as having a transfusion reduction response if there was a ≥ 50% decrease from pretreatment transfusion requirements (before the start of the study mediation) compared to any consecutive 56 days during the study (i.e. post treatment).
    Time FrameBaseline (Day -54 to Day 0), During study (Day 1 up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (MITT) diagnosis of low- or int-1-risk MDS associated with a del(5q) cytogenetic abnormality based on central hematologic and cytogenetic reviewers confirmation received ≥2 transfusions in each of the 8-week periods during the 16 week pre-treatment period received ≥1 dose of study drug
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants94
    Number [participant]
    70
    4. Secondary Outcome
    TitleTime to Transfusion Independence
    DescriptionTransfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Time to transfusion independence was defined as the day of the first dose of study drug to the first day of the first 56-day RBC transfusion-free period.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population who achieved transfusion independence
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants59
    Mean (Standard Deviation) [weeks]
    6.2
    (6.89)
    5. Secondary Outcome
    TitleParticipants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study
    DescriptionTransfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Participants who relapsed required a transfusion after the period of transfusion independence. Participants who maintained transfusion independence did not require a transfusion during the remainder of the study.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population who achieved transfusion independence
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants59
    Relapsed (had a transfusion after response)
    35
    23.6%
    Maintained transfusion independence
    24
    16.2%
    6. Secondary Outcome
    TitleKaplan Meier Estimate for Duration of Transfusion Independence Response
    DescriptionDuration of response is measured from the first of the consecutive 56 days during which the participant was free of RBC transfusions to the date of the first RBC transfusion after this period. Duration of response was censored at the date of last visit for participants who maintained transfusion independence.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population who achieved transfusion independence
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants59
    Median (95% Confidence Interval) [weeks]
    97.0
    7. Secondary Outcome
    TitleChange in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders
    DescriptionThe change from baseline in hemoglobin for participants who became RBC-transfusion independent. The maximum hemoglobin value obtained during the response period is used in the calculation of change from baseline.
    Time FrameBaseline (Day -54 to Day 0), During study (Day 1 up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population who achieved transfusion independence
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants59
    Mean (Standard Deviation) [g/dL]
    6.1
    (1.92)
    8. Secondary Outcome
    TitleParticipant Counts of Cytogenetic Response
    DescriptionParticipants deemed evaluable by the central cytogenetic review had their cytogenetic response categorized as major or minor. A major cytogenetic response was defined as ≥ 20 metaphases recorded at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with no abnormal metaphases observed. A minor cytogenetic response was defined as ≥ 20 metaphases analyzed at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with a ≥ 50% reduction in the proportion of hematopoietic cells with cytogenetic abnormalities compared with baseline.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Evaluable participants from the modified intent to treat population. Evaluable participants had ≥ 20 metaphases analyzed at baseline during the 56-day period immediately preceding the first day of study drug intake and ≥ 20 metaphases analyzed at least once at postbaseline visits.
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants52
    Major
    18
    12.2%
    Minor
    20
    13.5%
    None
    14
    9.5%
    9. Secondary Outcome
    TitleParticipant Counts of Platelet Response
    DescriptionMajor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3 in all values within 56 days of start of treatment, an absolute increase of ≥30,000/mm^3 sustained for ≥56 consecutive days. In platelet transfusion-dependent participants, a major response was stabilization of platelet counts and platelet transfusion independence. Minor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3, a ≥ 50% increase in platelet count with a net increase >10,000/mm^3 for a consecutive 56-day period in the absence of platelet transfusions.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Evaluable participants from the modified intent to treat population. Participants must have a baseline platelet count <100 * 10^9/L to be included in the analysis.
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants15
    Major
    2
    1.4%
    Minor
    0
    0%
    None
    13
    8.8%
    10. Secondary Outcome
    TitleParticipant Counts of Absolute Neutrophil Count (ANC) Response
    DescriptionMajor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3 in all values obtained within 56 days of start of treatment, a ≥ 100% increase or an absolute increase of ≥ 500/mm^3, whichever was greater (at least to be ≥ 500/mm^3), sustained for 56 consecutive days. Minor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3, an increase in ANC concentration of ≥ 100% sustained for 56 consecutive days.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Evaluable participants from the modified intent to treat population. Evaluable participants are required to have a baseline absolute neutrophil count (ANC) <1 * 10^9/L.
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants27
    Major
    9
    Minor
    0
    None
    18
    11. Secondary Outcome
    TitleParticipants With Complete or Partial Bone Marrow Improvement
    DescriptionBone marrow aspirates were assessed by a central reviewer. A complete bone marrow improvement required a baseline French-American-British (FAB) classification (see Baseline Characteristics) of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) and a during study assessment of no MDS. A partial bone marrow improvement reflected an improved FAB classification compared to baseline (e.g. RARS to RA) but evidence of MDS continued to exist.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population of participants with adequate bone marrow aspirate at baseline.
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants94
    Complete bone marrow improvement
    22
    14.9%
    Partial bone marrow improvement
    15
    10.1%
    12. Secondary Outcome
    TitleParticipants With Bone Marrow Progression
    DescriptionBone marrow aspirate was assessed by a central reviewer. Progression is represented in two categories according to changes from baseline in French-American-British (FAB) classification (see Baseline Characteristics): Baseline classification of refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) to a during treatment (plus 30 days) classification of refractory anemia with excess blasts (RAEB). Any baseline FAB classification to a during treatment (plus 30 days) classification of acute myeloid leukemia (AML).
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population of participants with adequate bone marrow aspirate at baseline.
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    Measure Participants94
    RA/RARS to RAEB
    11
    7.4%
    RA/RARS/RAEB/CMML to AML
    6
    4.1%

    Adverse Events

    Time FrameUp to 2 years
    Adverse Event Reporting Description
    Arm/Group TitleLenalidomide
    Arm/Group DescriptionThe protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.
    All Cause Mortality
    Lenalidomide
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    Lenalidomide
    Affected / at Risk (%)# Events
    Total89/148 (60.1%)
    Blood and lymphatic system disorders
    Neutropenia10/148 (6.8%)
    Anaemia NOS8/148 (5.4%)
    Febrile Neutropenia8/148 (5.4%)
    Thrombocytopenia6/148 (4.1%)
    Leukopenia NOS3/148 (2%)
    Pancytopenia3/148 (2%)
    Coagulopathy1/148 (0.7%)
    Cardiac disorders
    Cardiac Failure Congestive6/148 (4.1%)
    Atrial Fibrillation3/148 (2%)
    Cardiac Failure NOS2/148 (1.4%)
    Myocardial Infarction2/148 (1.4%)
    Cardio-Respiratory Arrest1/148 (0.7%)
    Cardiomyopathy NOS1/148 (0.7%)
    Diastolic Dysfunction1/148 (0.7%)
    Pulmonary Oedema NOS1/148 (0.7%)
    Tachyarrhythmia1/148 (0.7%)
    Ear and labyrinth disorders
    Vertigo1/148 (0.7%)
    Gastrointestinal disorders
    Vomiting NOS5/148 (3.4%)
    Abdominal Pain NOS4/148 (2.7%)
    Diarrhoea NOS4/148 (2.7%)
    Gastroenteritis NOS3/148 (2%)
    Nausea3/148 (2%)
    Rectal Haemorrhage2/148 (1.4%)
    Colitis Ischaemic1/148 (0.7%)
    Colonic Polyp1/148 (0.7%)
    Constipation1/148 (0.7%)
    Dysphagia1/148 (0.7%)
    Gastritis NOS1/148 (0.7%)
    Gastrooesophageal Reflux Disease1/148 (0.7%)
    Hiatus Hernia1/148 (0.7%)
    Intestinal Perforation NOS1/148 (0.7%)
    Irritable Bowel Syndrome1/148 (0.7%)
    Oesophageal Perforation1/148 (0.7%)
    Perirectal Abscess1/148 (0.7%)
    General disorders
    Pyrexia4/148 (2.7%)
    Asthenia2/148 (1.4%)
    Fall2/148 (1.4%)
    Fatigue2/148 (1.4%)
    Multi-Organ Failure2/148 (1.4%)
    Chest Pain1/148 (0.7%)
    Intermittent Pyrexia1/148 (0.7%)
    Rigors1/148 (0.7%)
    Sudden Death1/148 (0.7%)
    Hepatobiliary disorders
    Cholecystitis NOS1/148 (0.7%)
    Hyperbilirubinaemia1/148 (0.7%)
    Immune system disorders
    Hypersensitivity NOS1/148 (0.7%)
    Infections and infestations
    Pneumonia Not Otherwise Specified (NOS)15/148 (10.1%)
    Sepsis NOS6/148 (4.1%)
    Bacteraemia2/148 (1.4%)
    Cellulitis2/148 (1.4%)
    Infection NOS2/148 (1.4%)
    Urinary Tract Infection NOS2/148 (1.4%)
    Bronchitis Acute NOS1/148 (0.7%)
    Central Line Infection1/148 (0.7%)
    Clostridial Infection NOS1/148 (0.7%)
    Enterobacter Sepsis1/148 (0.7%)
    Groin Infection1/148 (0.7%)
    Herpes Zoster1/148 (0.7%)
    Influenza1/148 (0.7%)
    Klebsiella Sepsis1/148 (0.7%)
    Lobar Pneumonia NOS1/148 (0.7%)
    Post Procedural Site Wound Infection1/148 (0.7%)
    Sinusitis Acute NOS1/148 (0.7%)
    Sinusitis NOS1/148 (0.7%)
    Vaginosis Fungal NOS1/148 (0.7%)
    Injury, poisoning and procedural complications
    Femoral Neck Fracture2/148 (1.4%)
    Femur Fracture2/148 (1.4%)
    Medical Device Complication2/148 (1.4%)
    Comminuted Fracture1/148 (0.7%)
    Hip Fracture1/148 (0.7%)
    Overdose NOS1/148 (0.7%)
    Spinal Compression Fracture1/148 (0.7%)
    Investigations
    Blood Creatinine Increased1/148 (0.7%)
    Troponin I Increased1/148 (0.7%)
    Metabolism and nutrition disorders
    Dehydration8/148 (5.4%)
    Hypernatraemia1/148 (0.7%)
    Hypoglycaemia NOS1/148 (0.7%)
    Musculoskeletal and connective tissue disorders
    Arthrlagia1/148 (0.7%)
    Back Pain1/148 (0.7%)
    Localised Osteoarthritis1/148 (0.7%)
    Osteolysis1/148 (0.7%)
    Periarthritis1/148 (0.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Leukaemia NOS7/148 (4.7%)
    Acute Myeloid Leukaemia NOS3/148 (2%)
    B-Cell Lymphoma NOS1/148 (0.7%)
    Carcinoid Tumour of the Small Bowel1/148 (0.7%)
    Lung Cancer Metastatic1/148 (0.7%)
    Multiple Myeloma1/148 (0.7%)
    Ovarian Cancer NOS1/148 (0.7%)
    Refractory Anaemia with Excess Blasts in Transformation1/148 (0.7%)
    Thymoma NOS1/148 (0.7%)
    Nervous system disorders
    Dizziness3/148 (2%)
    Cerebrovascular Accident2/148 (1.4%)
    Depressed Level of Consciousness2/148 (1.4%)
    Syncope2/148 (1.4%)
    Transient Ischaemic Attack2/148 (1.4%)
    Aphasia1/148 (0.7%)
    Cerebral Haemorrhage1/148 (0.7%)
    Convulsions NOS1/148 (0.7%)
    Dementia NOS1/148 (0.7%)
    Headache1/148 (0.7%)
    Hypertensive Encephalopathy1/148 (0.7%)
    Migraine NOS1/148 (0.7%)
    Senile Dementia NOS1/148 (0.7%)
    Subarachnoid Haemorrhage NOS1/148 (0.7%)
    Subdural Haematoma1/148 (0.7%)
    Renal and urinary disorders
    Renal Failure NOS2/148 (1.4%)
    Azotaemia1/148 (0.7%)
    Renal Failure Acute1/148 (0.7%)
    Reproductive system and breast disorders
    Cervical Dysplasia1/148 (0.7%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism5/148 (3.4%)
    Dyspnoea NOS2/148 (1.4%)
    Pleural Effusion2/148 (1.4%)
    Pneumonitis NOS2/148 (1.4%)
    Pulmonary Hypertension NOS2/148 (1.4%)
    Asthma NOS1/148 (0.7%)
    Chronic Obstructive Airways Disease Exacerbated1/148 (0.7%)
    Epistaxis1/148 (0.7%)
    Lung Infiltration NOS1/148 (0.7%)
    Respiratory Distress1/148 (0.7%)
    Respiratory Failure1/148 (0.7%)
    Skin and subcutaneous tissue disorders
    Rash NOS2/148 (1.4%)
    Acute Febrile Neutrophilic Dermatosis1/148 (0.7%)
    Dermatitis Medicamentosa1/148 (0.7%)
    Vascular disorders
    Deep Vein Thrombosis5/148 (3.4%)
    Hypotension NOS1/148 (0.7%)
    Peripheral Ischaemia1/148 (0.7%)
    Thrombophlebitis Superficial1/148 (0.7%)
    Other (Not Including Serious) Adverse Events
    Lenalidomide
    Affected / at Risk (%)# Events
    Total148/148 (100%)
    Blood and lymphatic system disorders
    Thrombocytopenia93/148 (62.8%)
    Neutropenia91/148 (61.5%)
    Anaemia NOS32/148 (21.6%)
    Leukopenia NOS19/148 (12.8%)
    Cardiac disorders
    Palpitations10/148 (6.8%)
    Endocrine disorders
    Acquired Hypothyroidism14/148 (9.5%)
    Eye disorders
    Conjunctivitis9/148 (6.1%)
    Vision Blurred8/148 (5.4%)
    Gastrointestinal disorders
    Diarrhoea Not Otherwise Specified (NOS)87/148 (58.8%)
    Nausea41/148 (27.7%)
    Constipation39/148 (26.4%)
    Abdominal Pain NOS24/148 (16.2%)
    Vomiting NOS18/148 (12.2%)
    Abdominal Pain Upper14/148 (9.5%)
    Dry Mouth12/148 (8.1%)
    Loose Stools12/148 (8.1%)
    Toothache11/148 (7.4%)
    Flatulence8/148 (5.4%)
    General disorders
    Fatigue62/148 (41.9%)
    Oedema Peripheral40/148 (27%)
    Pyrexia37/148 (25%)
    Asthenia22/148 (14.9%)
    Oedema NOS18/148 (12.2%)
    Pain NOS14/148 (9.5%)
    Fall13/148 (8.8%)
    Chest Pain11/148 (7.4%)
    Rigors9/148 (6.1%)
    Infections and infestations
    Upper Respiratory Tract Infection NOS33/148 (22.3%)
    Urinary Tract Infection NOS21/148 (14.2%)
    Sinusitis NOS19/148 (12.8%)
    Cellulitis12/148 (8.1%)
    Influenza11/148 (7.4%)
    Herpes Simplex8/148 (5.4%)
    Investigations
    Alanine Aminotransferase Increased12/148 (8.1%)
    Weight Decreased12/148 (8.1%)
    Metabolism and nutrition disorders
    Hypokalaemia22/148 (14.9%)
    Anorexia20/148 (13.5%)
    Hypomagnesaemia11/148 (7.4%)
    Appetite Decreased NOS8/148 (5.4%)
    Hypocalcaemia8/148 (5.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia46/148 (31.1%)
    Back Pain39/148 (26.4%)
    Muscle Cramp31/148 (20.9%)
    Pain in Limb25/148 (16.9%)
    Myalgia19/148 (12.8%)
    Peripheral Swelling14/148 (9.5%)
    Pain in Foot10/148 (6.8%)
    Neck Pain8/148 (5.4%)
    Nervous system disorders
    Dizziness35/148 (23.6%)
    Headache33/148 (22.3%)
    Hypoaesthesia11/148 (7.4%)
    Dysgeusia10/148 (6.8%)
    Paraesthesia10/148 (6.8%)
    Peripheral Neuropathy NOS10/148 (6.8%)
    Peripheral Sensory Neuropathy8/148 (5.4%)
    Psychiatric disorders
    Insomnia19/148 (12.8%)
    Depression14/148 (9.5%)
    Anxiety8/148 (5.4%)
    Renal and urinary disorders
    Dysuria12/148 (8.1%)
    Respiratory, thoracic and mediastinal disorders
    Nasopharyngitis44/148 (29.7%)
    Cough38/148 (25.7%)
    Dyspnoea NOS37/148 (25%)
    Pharyngitis29/148 (19.6%)
    Epistaxis24/148 (16.2%)
    Bronchitis NOS17/148 (11.5%)
    Dyspnoea Exertional16/148 (10.8%)
    Rhinitis NOS12/148 (8.1%)
    Rhinorrhoea8/148 (5.4%)
    Skin and subcutaneous tissue disorders
    Pruritus66/148 (44.6%)
    Rash NOS54/148 (36.5%)
    Dry Skin21/148 (14.2%)
    Contusion18/148 (12.2%)
    Night Sweats16/148 (10.8%)
    Sweating Increased13/148 (8.8%)
    Erythema12/148 (8.1%)
    Alopecia10/148 (6.8%)
    Ecchymosis10/148 (6.8%)
    Skin Lesions NOS8/148 (5.4%)
    Vascular disorders
    Hypertension NOS13/148 (8.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Unless approved by Celgene, single center data will not be published before multicenter data, unless more than 1 year has elapsed since completion of the Study. Thereafter, Investigator may publish single center data provided that Investigator shall: i) provide a copy of the publication to Celgene at least 60 days in advance of submission for publication; ii) delete Celgene Confidential Information and; iii) delay submission up to 90 additional days to permit intellectual property filings.

    Results Point of Contact

    Name/TitleAssociate Director, Clinical Trials Disclosure
    OrganizationCelgene Corporation
    Phone1-888-260-1599
    Emailclinicaltrialdisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00065156
    Other Study ID Numbers:
    • CC-5013-MDS-003
    • NCT00074126
    First Posted:
    Jul 18, 2003
    Last Update Posted:
    Nov 19, 2019
    Last Verified:
    Nov 1, 2019