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A Phase 1b/2, Dose-Escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Relapsed Multiple Myeloma

Sponsor
AbbVie (prior sponsor, Abbott) (Industry)
Overall Status
Completed
CT.gov ID
NCT00742560
Collaborator
Bristol-Myers Squibb (Industry)
101
Enrollment
5
Arms
98
Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the combination of elotuzumab, lenalidomide, and dexamethasone in subjects with relapsed multiple myeloma.

Condition or Disease Intervention/Treatment Phase
  • Biological: elotuzumab
  • Drug: lenalidomide
  • Drug: dexamethasone oral
  • Drug: dexamethasone injection
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2, Multicenter, Open-label, Dose-escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed Multiple Myeloma
Study Start Date :
Aug 1, 2008
Actual Primary Completion Date :
Oct 1, 2016
Actual Study Completion Date :
Oct 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

Biological: elotuzumab
Humanized Anti-CS1 Monoclonal IgG1 Antibody (HuLuc63) administered as an intravenous infusion once a week during Cycles 1 and 2, and every other week beginning with Cycle 3.
Other Names:
  • HuLuc63

    • Drug: lenalidomide
    Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle

    Drug: dexamethasone oral
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)

    Drug: dexamethasone injection
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)
    Experimental: Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

    Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

    Biological: elotuzumab
    Humanized Anti-CS1 Monoclonal IgG1 Antibody (HuLuc63) administered as an intravenous infusion once a week during Cycles 1 and 2, and every other week beginning with Cycle 3.
    Other Names:
  • HuLuc63

    • Drug: lenalidomide
    Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle

    Drug: dexamethasone oral
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)

    Drug: dexamethasone injection
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)
    Experimental: Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

    Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

    Biological: elotuzumab
    Humanized Anti-CS1 Monoclonal IgG1 Antibody (HuLuc63) administered as an intravenous infusion once a week during Cycles 1 and 2, and every other week beginning with Cycle 3.
    Other Names:
  • HuLuc63

    • Drug: lenalidomide
    Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle

    Drug: dexamethasone oral
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)

    Drug: dexamethasone injection
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)
    Experimental: Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2)

    Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

    Biological: elotuzumab
    Humanized Anti-CS1 Monoclonal IgG1 Antibody (HuLuc63) administered as an intravenous infusion once a week during Cycles 1 and 2, and every other week beginning with Cycle 3.
    Other Names:
  • HuLuc63

    • Drug: lenalidomide
    Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle

    Drug: dexamethasone oral
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)

    Drug: dexamethasone injection
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)
    Experimental: Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)

    Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

    Biological: elotuzumab
    Humanized Anti-CS1 Monoclonal IgG1 Antibody (HuLuc63) administered as an intravenous infusion once a week during Cycles 1 and 2, and every other week beginning with Cycle 3.
    Other Names:
  • HuLuc63

    • Drug: lenalidomide
    Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle

    Drug: dexamethasone oral
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)

    Drug: dexamethasone injection
    Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Lenalidomide and Dexamethasone (Phase 1) [4 weeks]

      MTD was determined by testing increasing doses up to 20 mg/kg once daily dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (dose limiting toxicity [DLT]) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria for Adverse Events (CTCAE) Grade 4 neutropenia in specific conditions, platelets < 10,000 cells/mm^3 that do not recover to 25,000 cells/mm^3; and specific non-hematologic/biochemical toxicities CTCAE Grade 3 or 4 (except fatigue and Grade 3 infections); CTCAE version 3.0 were used.

    2. Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 2) [From date of randomization until 60 days following the last infusion (or before initiation of new therapy), up to 101 months]

      ORR: Percentage of participants with confirmed complete response (CR; negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow), partial response (PR; ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to ≤200 mg per 24 hour; if serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC] levels is required in place of the M-protein criteria; if serum and urine M-protein are unmeasurable, and serum FLC is also unmeasurable, a ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%; and, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas), very good PR (VGPR; normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence), or stringent CR (sCR; CR plus VGPR).

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 1) [From first dose of elotuzumab until 60 days following the last infusion (or before initiation of new therapy), up to 100.5 months]

      ORR: Percentage of participants with confirmed complete response (CR; negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow), partial response (PR; ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to ≤200 mg per 24 hour; if serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC] levels is required in place of the M-protein criteria; if serum and urine M-protein are unmeasurable, and serum FLC is also unmeasurable, a ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%; and, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas), very good PR (VGPR; normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence), or stringent CR (sCR; CR plus VGPR).

    2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 60 days after the last dose of study drug (up to 95 months)]

      An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either definitely related, probably related, possibly related or unrelated. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.

    3. Number of Participants With Infusion Reactions [Cycles 1 and 2: Days 1, 8, 15, and 22 (day of infusion of elotuzumab) and Days 2, 9, 16, and 23 (day following infusion); and Cycles 3 and greater: Days 1 and 15 (day of infusion) and Days 2 and 16 (day after infusion) (up to 95 months)]

      During Phase 1, a list of 118 pre-defined MedDRA preferred terms that had been adjudicated to be clinically relevant to infusion reactions by a safety committee was used to search for TEAEs that could potentially be associated with an infusion reaction following elotuzumab administration. Examples of these terms included angioedema, bronchospasm, chills, flushing, pyrexia, rash and urticaria. During Phase 2, the method for capturing TEAEs associated with an infusion reaction was modified to include investigators' designation of AEs judged as clinically relevant infusion reactions. The number of participants infusion reactions are provided overall and by highest toxicity grade (CTCAE v 3.0).

    4. Mean Serum Concentrations of Elotuzumab During Cycle 1 [Cycle 1: Days 1 (pre-infusion and 0.5, 2 and 4 hours post-infusion), 8 (pre-infusion and 0.5 and 2 hours post-infusion), 15 (pre-infusion and 0.5 hours and 2 hours post-infusion), and 22 (pre-infusion and 0.5, 2, and 4 hours post-infusion)]

      Blood samples were collected during Phase 1, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours) and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). Blood samples were collected during Phase 2, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) and 2 hours post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). The samples were analyzed for the concentration of elotuzumab using validated analytical methods. Mean serum concentrations on Cycle 1, Days 1, 8, 15, and 22 (measured in μg/mL) are reported overall (across Phase 1 and Phase 2) by dose.

    5. Maximum Serum Concentration (Cmax) of Elotuzumab [Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1]

      The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.

    6. Area Under the Concentration-time Curve From 0 to Infinity (AUC0-inf) of Elotuzumab [Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1]

      The area under the plasma concentration-time curve (AUC; measured in ng*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.

    7. Systemic Clearance (CL) of Elotuzumab [Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1]

      Systemic clearance (CL, measured in mL/kg/hr) is a measure of the efficiency with which a drug is irreversibly removed from the body. The CL of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.

    8. Volume of Distribution (V) of Elotuzumab [Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1]

      Volume of distribution (V, measured in L/kg) is the hypothetical volume of body fluid that would be required to dissolve the amount of drug needed to achieve the same concentration in the blood. The V of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.

    9. Serum Half-life (t1/2) of Elotuzumab [Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1]

      The serum half-life of a drug (t1/2, measured in hours) is the time necessary to reduce the plasma concentration by half. The t1/2 of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.

    10. Duration of Response [From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months]

      Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first. The distribution of duration of response was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the duration of response distribution are provided.

    11. Time to Progression (TTP) [From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months]

      TTP is defined as the time from first dose (phase 1) or time from randomization (phase 2) to disease progression. The distribution of TTP was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the TTP distribution are provided.

    12. Progression-free Survival (PFS) [From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months]

      PFS is defined as the time from first dose (phase 1) or time from randomization (phase 2) to disease progression or death. The distribution of PFS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the PFS distribution are provided.

    13. Percentage of Participants With Treatment-emergent Anti-elotuzumab Antibody (ADA) [From screening through 60-day follow up period (up to 101 months)]

      Treatment-emergent (post-dose) positive elotuzumab-specific ADA is differentiated from pre-existing (positive at the predose time point) positive elotuzumab-specific ADA. The percentage of participants with confirmed treatment-emergent ADA overall by dose is provided.

    14. Plasma Cell Myeloma Cytogenetic Subtype [Screening (up to 14 days prior to dosing)]

      Plasma cell myeloma cytogenetic subtype was assessed at the screening visit using standard karyotyping and/or fluorescence in situ hybridization. The number of participants in each cytogenetic risk category are provided: High Risk (International Staging System [ISS] stage II or III and t(4;14) or del(17p) abnormality); Standard Risk (not high or low risk); and Low Risk (ISS stage I or II and absence of t(4;14), del(17p) and 1q21 abnormalities AND age < 55).

    Eligibility Criteria

    Criteria

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

    1. Age 18 years or older with a confirmed diagnosis of multiple myeloma (MM) and documentation of one to three prior therapies.

    2. Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior treatment.

    3. Measurable monoclonal (M-) protein component in serum (≥ 0.5 g/dL) and/or urine (if present), (≥ 0.2 g excreted in a 24 hour collection sample). Subjects with free light chain only disease are excluded.

    4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

    5. Creatinine clearance ≥ 50 mL/min measured by Cockcroft-Gault method.

    6. Hematologic parameters defined by:

    • Absolute neutrophil count >1000 cells/mm^3 without growth factors for 7 days.

    • Platelets ≥ 75,000 cells/mm3 (75 × 109/L), without platelet transfusion, within 72 hours of screening evaluation.

    • Hemoglobin ≥ 8 g/dL without red blood cell transfusion within 72 hours of screening.

    1. Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) < 3 × upper limit of normal.

    2. Total bilirubin < 2 × upper limit of normal, direct bilirubin < 2.0 mg/dL.

    3. Negative urine pregnancy test in women of childbearing potential at screening and prior to prescribing lenalidomide. Females of childbearing potential (FCBP) must either commit to continued abstinence from heterosexual intercourse or begin acceptable methods of birth control for 28 days prior to prescribing lenalidomide. Men must agree to use a latex condom during sexual contact with FCBP even if they have had a successful vasectomy, and must agree not to donate semen during study drug therapy and for a period of time after therapy.

    4. Able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject's privacy regulations).

    5. Able to take aspirin daily as prophylactic anticoagulation therapy (subjects intolerant to aspirin may use warfarin or low-molecular-weight heparin).

    Exclusion Criteria:

    1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years.

    2. Active or prior plasma cell leukemia (defined as either 20% of peripheral WBC comprised of plasma/CD138+ cells or an absolute count of 2 x 10^9/L).

    3. Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure.

    4. Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.

    5. Treatment with any investigational drug within 2 weeks or 3 half lives (whichever is longer) of the first dose of elotuzumab.

    6. Use of corticosteroids, thalidomide, bortezomib, or cytotoxic chemotherapy within 2 weeks of the first dose of elotuzumab except for steroids with little or no systemic absorption (ie, topical or inhaled steroids).

    7. Prior lenalidomide therapy.

    8. Prior peripheral stem-cell transplant within 12 weeks of the first dose of elotuzumab.

    9. Treatment with nitrosoureas, such as carmustine (BiCNU), nitrogen mustard agents, or melphalan, within 6 weeks of first dose of elotuzumab.

    10. Neuropathy ≥ Grade 3 or painful neuropathy ≥ Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v3.0).

    11. Known active infections requiring IV antibiotic, antiviral, or antifungal therapy.

    12. Hypersensitivity to recombinant proteins or excipients in elotuzumab, lenalidomide, or dexamethasone.

    13. Female subjects who are pregnant or breastfeeding.

    14. Subjects with serum calcium (corrected for albumin) ≥ 12 mg/dL.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • AbbVie (prior sponsor, Abbott)
    • Bristol-Myers Squibb

    Investigators

    • Study Director: AbbVie Inc, AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT00742560
    Other Study ID Numbers:
    • HuLuc63-1703
    • 2007-006677-83
    First Posted:
    Aug 27, 2008
    Last Update Posted:
    Jan 10, 2018
    Last Verified:
    Jan 1, 2018
    Keywords provided by AbbVie (prior sponsor, Abbott)
    Multiple Myeloma
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Hematologic Neoplasms
    Dexamethasone
    Dexamethasone acetate
    Lenalidomide
    Elotuzumab
    BB 1101

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 101 participants were randomized (intent-to-treat [ITT] population); 1 subject did not receive study drug and is excluded from the analyses.
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Period Title: Overall Study
    STARTED 3 3 22 36 37
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 3 3 22 36 37

    Baseline Characteristics

    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Total
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Total of all reporting groups
    Overall Participants 3 3 22 36 37 101
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.3
    (7.23)
    64.7
    (6.94)
    59.3
    (10.87)
    60.6
    (9.70)
    63.3
    (9.76)
    61.7
    (9.91)
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    1
    33.3%
    10
    45.5%
    19
    52.8%
    24
    64.9%
    56
    55.4%
    Male
    1
    33.3%
    2
    66.7%
    12
    54.5%
    17
    47.2%
    13
    35.1%
    45
    44.6%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Lenalidomide and Dexamethasone (Phase 1)
    Description MTD was determined by testing increasing doses up to 20 mg/kg once daily dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (dose limiting toxicity [DLT]) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria for Adverse Events (CTCAE) Grade 4 neutropenia in specific conditions, platelets < 10,000 cells/mm^3 that do not recover to 25,000 cells/mm^3; and specific non-hematologic/biochemical toxicities CTCAE Grade 3 or 4 (except fatigue and Grade 3 infections); CTCAE version 3.0 were used.
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in the safety population (all randomized participants who received at least 1 dose of study drug) in the escalation cohorts (Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone [Phase 1]; Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone [Phase 1]; and Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone [Phase 1]).
    Arm/Group Title Phase 1 Elotuzumab + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab (5, 10, or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 28
    Number [mg/kg]
    20
    2. Primary Outcome
    Title Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 2)
    Description ORR: Percentage of participants with confirmed complete response (CR; negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow), partial response (PR; ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to ≤200 mg per 24 hour; if serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC] levels is required in place of the M-protein criteria; if serum and urine M-protein are unmeasurable, and serum FLC is also unmeasurable, a ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%; and, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas), very good PR (VGPR; normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence), or stringent CR (sCR; CR plus VGPR).
    Time Frame From date of randomization until 60 days following the last infusion (or before initiation of new therapy), up to 101 months

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Total (Phase 2)
    Arm/Group Description Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (10 or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 36 37 73
    Number (95% Confidence Interval) [percentage of participants]
    91.7
    3056.7%
    75.7
    2523.3%
    83.6
    380%
    3. Secondary Outcome
    Title Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 1)
    Description ORR: Percentage of participants with confirmed complete response (CR; negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow), partial response (PR; ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to ≤200 mg per 24 hour; if serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC] levels is required in place of the M-protein criteria; if serum and urine M-protein are unmeasurable, and serum FLC is also unmeasurable, a ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%; and, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas), very good PR (VGPR; normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence), or stringent CR (sCR; CR plus VGPR).
    Time Frame From first dose of elotuzumab until 60 days following the last infusion (or before initiation of new therapy), up to 100.5 months

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Total (Phase 1)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally Elotuzumab (5, 10, or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 3 22 28
    Number (95% Confidence Interval) [percentage of participants]
    100
    3333.3%
    100
    3333.3%
    77.3
    351.4%
    82.1
    228.1%
    4. Secondary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events (TEAEs)
    Description An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either definitely related, probably related, possibly related or unrelated. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
    Time Frame Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 60 days after the last dose of study drug (up to 95 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 3 22 36 37
    Any TEAE
    3
    100%
    3
    100%
    22
    100%
    36
    100%
    37
    100%
    Any TESAE
    0
    0%
    3
    100%
    12
    54.5%
    21
    58.3%
    21
    56.8%
    TEAEs ≥ Grade 3
    2
    66.7%
    3
    100%
    19
    86.4%
    32
    88.9%
    25
    67.6%
    TEAEs related to study drug
    3
    100%
    3
    100%
    16
    72.7%
    29
    80.6%
    26
    70.3%
    TESAEs related to study drug
    0
    0%
    0
    0%
    2
    9.1%
    2
    5.6%
    5
    13.5%
    5. Secondary Outcome
    Title Number of Participants With Infusion Reactions
    Description During Phase 1, a list of 118 pre-defined MedDRA preferred terms that had been adjudicated to be clinically relevant to infusion reactions by a safety committee was used to search for TEAEs that could potentially be associated with an infusion reaction following elotuzumab administration. Examples of these terms included angioedema, bronchospasm, chills, flushing, pyrexia, rash and urticaria. During Phase 2, the method for capturing TEAEs associated with an infusion reaction was modified to include investigators' designation of AEs judged as clinically relevant infusion reactions. The number of participants infusion reactions are provided overall and by highest toxicity grade (CTCAE v 3.0).
    Time Frame Cycles 1 and 2: Days 1, 8, 15, and 22 (day of infusion of elotuzumab) and Days 2, 9, 16, and 23 (day following infusion); and Cycles 3 and greater: Days 1 and 15 (day of infusion) and Days 2 and 16 (day after infusion) (up to 95 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 3 22 36 37
    Any reaction
    2
    66.7%
    3
    100%
    20
    90.9%
    5
    13.9%
    3
    8.1%
    Grade 5
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Grade 4
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    0
    0%
    Grade 3
    0
    0%
    0
    0%
    2
    9.1%
    1
    2.8%
    0
    0%
    Grade 2
    0
    0%
    1
    33.3%
    5
    22.7%
    1
    2.8%
    1
    2.7%
    Grade 1
    2
    66.7%
    2
    66.7%
    12
    54.5%
    3
    8.3%
    2
    5.4%
    6. Secondary Outcome
    Title Mean Serum Concentrations of Elotuzumab During Cycle 1
    Description Blood samples were collected during Phase 1, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours) and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). Blood samples were collected during Phase 2, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) and 2 hours post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). The samples were analyzed for the concentration of elotuzumab using validated analytical methods. Mean serum concentrations on Cycle 1, Days 1, 8, 15, and 22 (measured in μg/mL) are reported overall (across Phase 1 and Phase 2) by dose.
    Time Frame Cycle 1: Days 1 (pre-infusion and 0.5, 2 and 4 hours post-infusion), 8 (pre-infusion and 0.5 and 2 hours post-infusion), 15 (pre-infusion and 0.5 hours and 2 hours post-infusion), and 22 (pre-infusion and 0.5, 2, and 4 hours post-infusion)

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug, with evaluable data at given time point.
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2.
    Measure Participants 3 39 58
    Day 1: 0 hours
    0.00
    (0.00)
    0.00
    (0.00)
    0.00
    (0.00)
    Day 1: 0.5 hours
    78.48
    (21.33)
    217.90
    (99.31)
    434.20
    (202.74)
    Day 1: 2 hours
    213.31
    (91.30)
    388.58
    (112.94)
    Day 1: 4 hours
    85.56
    (23.54)
    251.34
    (31.92)
    525.98
    (188.46)
    Day 8: 0 hours
    32.44
    (8.91)
    92.47
    (61.16)
    168.55
    (56.43)
    Day 8: 0.5 hours
    133.37
    (40.87)
    281.53
    (117.35)
    593.80
    (192.70)
    Day 8: 2 hours
    268.35
    (107.44)
    520.97
    (207.28)
    Day 15: 0 hours
    49.84
    (28.28)
    111.11
    (56.36)
    298.82
    (231.17)
    Day 15: 0.5 hours
    140.09
    (32.28)
    282.29
    (100.29)
    661.91
    (251.08)
    Day 22: 0 hours
    61.93
    (53.66)
    135.92
    (106.83)
    308.02
    (144.61)
    Day 22: 0.5 hours
    168.61
    (59.31)
    310.03
    (165.14)
    699.70
    (230.41)
    Day 22: 2 hours
    268.53
    (NA)
    298.85
    (114.35)
    704.48
    (234.98)
    Day 22: 4 hours
    128.94
    (42.04)
    538.88
    (195.35)
    981.16
    (280.28)
    7. Secondary Outcome
    Title Maximum Serum Concentration (Cmax) of Elotuzumab
    Description The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.
    Time Frame Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1

    Outcome Measure Data

    Analysis Population Description
    No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated (collected data not reliable due to assay limitations caused by sparse serum concentrations).
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2.
    Measure Participants 0 0 0
    8. Secondary Outcome
    Title Area Under the Concentration-time Curve From 0 to Infinity (AUC0-inf) of Elotuzumab
    Description The area under the plasma concentration-time curve (AUC; measured in ng*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.
    Time Frame Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1

    Outcome Measure Data

    Analysis Population Description
    No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated (collected data not reliable due to assay limitations caused by sparse serum concentrations).
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2.
    Measure Participants 0 0 0
    9. Secondary Outcome
    Title Systemic Clearance (CL) of Elotuzumab
    Description Systemic clearance (CL, measured in mL/kg/hr) is a measure of the efficiency with which a drug is irreversibly removed from the body. The CL of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.
    Time Frame Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1

    Outcome Measure Data

    Analysis Population Description
    No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated (collected data not reliable due to assay limitations caused by sparse serum concentrations).
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2.
    Measure Participants 0 0 0
    10. Secondary Outcome
    Title Volume of Distribution (V) of Elotuzumab
    Description Volume of distribution (V, measured in L/kg) is the hypothetical volume of body fluid that would be required to dissolve the amount of drug needed to achieve the same concentration in the blood. The V of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.
    Time Frame Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1

    Outcome Measure Data

    Analysis Population Description
    No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated (collected data not reliable due to assay limitations caused by sparse serum concentrations).
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2.
    Measure Participants 0 0 0
    11. Secondary Outcome
    Title Serum Half-life (t1/2) of Elotuzumab
    Description The serum half-life of a drug (t1/2, measured in hours) is the time necessary to reduce the plasma concentration by half. The t1/2 of elotuzumab was to be estimated using non-compartmental methods and data reported as the mean ± standard deviation. No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated due to sparse serum concentration collections.
    Time Frame Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1

    Outcome Measure Data

    Analysis Population Description
    No noncompartmental pharmacokinetic parameters (e.g., AUC, CL, V, t 1/2) were estimated (collected data not reliable due to assay limitations caused by sparse serum concentrations).
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 5 mg/kg Administered as an IV Infusion in Combinati Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally in Phase 1 and Phase 2.
    Measure Participants 0 0 0
    12. Secondary Outcome
    Title Duration of Response
    Description Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first. The distribution of duration of response was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the duration of response distribution are provided.
    Time Frame From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Total (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Total (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (5, 10, or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (10 or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally
    Measure Participants 3 3 22 28 36 37 73
    Median (95% Confidence Interval) [months]
    4.47
    9.92
    NA
    NA
    34.83
    29.01
    29.24
    13. Secondary Outcome
    Title Time to Progression (TTP)
    Description TTP is defined as the time from first dose (phase 1) or time from randomization (phase 2) to disease progression. The distribution of TTP was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the TTP distribution are provided.
    Time Frame From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Total (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Total (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (5, 10, or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (10 or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 3 22 28 36 37 73
    Median (95% Confidence Interval) [months]
    6.08
    11.53
    52.93
    52.93
    32.49
    19.94
    28.16
    14. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description PFS is defined as the time from first dose (phase 1) or time from randomization (phase 2) to disease progression or death. The distribution of PFS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the PFS distribution are provided.
    Time Frame From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Total (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 10 mg/kg Administered as an IV Infusion in Combinat Total (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (5, 10, or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab (10 or 20 mg/kg) administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 3 22 28 36 37 73
    Median (95% Confidence Interval) [months]
    6.08
    22.23
    NA
    32.92
    32.49
    25.00
    28.62
    15. Secondary Outcome
    Title Percentage of Participants With Treatment-emergent Anti-elotuzumab Antibody (ADA)
    Description Treatment-emergent (post-dose) positive elotuzumab-specific ADA is differentiated from pre-existing (positive at the predose time point) positive elotuzumab-specific ADA. The percentage of participants with confirmed treatment-emergent ADA overall by dose is provided.
    Time Frame From screening through 60-day follow up period (up to 101 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and with at least one evaluable post-dose sample.
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 39 57
    Number [percentage of participants]
    0
    0%
    6
    200%
    5
    22.7%
    16. Secondary Outcome
    Title Plasma Cell Myeloma Cytogenetic Subtype
    Description Plasma cell myeloma cytogenetic subtype was assessed at the screening visit using standard karyotyping and/or fluorescence in situ hybridization. The number of participants in each cytogenetic risk category are provided: High Risk (International Staging System [ISS] stage II or III and t(4;14) or del(17p) abnormality); Standard Risk (not high or low risk); and Low Risk (ISS stage I or II and absence of t(4;14), del(17p) and 1q21 abnormalities AND age < 55).
    Time Frame Screening (up to 14 days prior to dosing)

    Outcome Measure Data

    Analysis Population Description
    Safety population: All randomized participants who received at least 1 dose of study drug
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    Measure Participants 3 3 22 36 37
    High Risk
    1
    33.3%
    0
    0%
    0
    0%
    1
    2.8%
    3
    8.1%
    Standard Risk
    2
    66.7%
    3
    100%
    17
    77.3%
    30
    83.3%
    24
    64.9%
    Low Risk
    0
    0%
    0
    0%
    3
    13.6%
    2
    5.6%
    3
    8.1%
    Not Reported
    0
    0%
    0
    0%
    2
    9.1%
    3
    8.3%
    7
    18.9%

    Adverse Events

    Time Frame Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 60 days after the last dose of study drug (up to 95 months).
    Adverse Event Reporting Description TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity after initiation of study drug until 30 days after the last dose of study drug.
    Arm/Group Title Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Arm/Group Description Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally. Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.
    All Cause Mortality
    Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 3/3 (100%) 12/22 (54.5%) 21/36 (58.3%) 21/37 (56.8%)
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 1/36 (2.8%) 2/37 (5.4%)
    LYMPHOPENIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    NEUTROPENIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 1/37 (2.7%)
    PANCYTOPENIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    Cardiac disorders
    ANGINA PECTORIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    ATRIAL FIBRILLATION 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 0/36 (0%) 1/37 (2.7%)
    BRADYCARDIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    TACHYCARDIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    Gastrointestinal disorders
    CONSTIPATION 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    DIARRHOEA 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    DIVERTICULAR PERFORATION 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    GASTROINTESTINAL HAEMORRHAGE 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    GASTROINTESTINAL PERFORATION 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    HAEMATEMESIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    NAUSEA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    VARICES OESOPHAGEAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    VOMITING 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    General disorders
    CHEST PAIN 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 1/37 (2.7%)
    MULTIPLE ORGAN DYSFUNCTION SYNDROME 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    PYREXIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    Hepatobiliary disorders
    CHOLECYSTITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    Immune system disorders
    ANAPHYLACTIC REACTION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    Infections and infestations
    ASPERGILLUS INFECTION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    BRONCHITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    CELLULITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    CLOSTRIDIUM DIFFICILE COLITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    H1N1 INFLUENZA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    HERPES ZOSTER 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    INFLUENZA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    LOCALISED INFECTION 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    LUNG INFECTION 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    MENINGITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    PNEUMONIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 5/37 (13.5%)
    PNEUMONIA KLEBSIELLA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    PNEUMONIA VIRAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    POSTOPERATIVE WOUND INFECTION 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    PYELONEPHRITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    SEPSIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 2/37 (5.4%)
    URINARY TRACT INFECTION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    VISCERAL LEISHMANIASIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    Injury, poisoning and procedural complications
    GASTROENTERITIS RADIATION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    Metabolism and nutrition disorders
    ELECTROLYTE IMBALANCE 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    HYPERCALCAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    HYPOKALAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    METABOLIC ACIDOSIS 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    BACK PAIN 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    BONE PAIN 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    MUSCULOSKELETAL PAIN 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    PAIN IN EXTREMITY 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BLADDER TRANSITIONAL CELL CARCINOMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    LOBULAR BREAST CARCINOMA IN SITU 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    MALIGNANT MELANOMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    MYELODYSPLASTIC SYNDROME 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 1/37 (2.7%)
    PROSTATE CANCER 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    SQUAMOUS CELL CARCINOMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    SQUAMOUS CELL CARCINOMA OF SKIN 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 1/37 (2.7%)
    Nervous system disorders
    CEREBROVASCULAR ACCIDENT 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    GENERALISED TONIC-CLONIC SEIZURE 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    SYNCOPE 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    TRANSIENT GLOBAL AMNESIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    TRANSIENT ISCHAEMIC ATTACK 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 1/37 (2.7%)
    Psychiatric disorders
    CONFUSIONAL STATE 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    RENAL COLIC 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    RENAL FAILURE 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    PROSTATITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    ASTHMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    LUNG DISORDER 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 0/37 (0%)
    PNEUMONITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    PULMONARY EMBOLISM 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 1/36 (2.8%) 1/37 (2.7%)
    STRIDOR 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    Skin and subcutaneous tissue disorders
    RASH 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    Vascular disorders
    ACCELERATED HYPERTENSION 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    DEEP VEIN THROMBOSIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 1/37 (2.7%)
    PHLEBITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    PHLEBITIS SUPERFICIAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    Other (Not Including Serious) Adverse Events
    Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 22/22 (100%) 36/36 (100%) 37/37 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 2/3 (66.7%) 2/3 (66.7%) 10/22 (45.5%) 17/36 (47.2%) 13/37 (35.1%)
    FEBRILE NEUTROPENIA 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 2/36 (5.6%) 3/37 (8.1%)
    HAEMOGLOBINAEMIA 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    INCREASED TENDENCY TO BRUISE 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    IRON DEFICIENCY ANAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    LEUKOPENIA 1/3 (33.3%) 1/3 (33.3%) 2/22 (9.1%) 8/36 (22.2%) 6/37 (16.2%)
    LYMPHADENOPATHY 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 2/37 (5.4%)
    LYMPHOPENIA 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 12/36 (33.3%) 8/37 (21.6%)
    NEUTROPENIA 2/3 (66.7%) 3/3 (100%) 7/22 (31.8%) 12/36 (33.3%) 9/37 (24.3%)
    PANCYTOPENIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 3/37 (8.1%)
    THROMBOCYTOPENIA 1/3 (33.3%) 2/3 (66.7%) 5/22 (22.7%) 12/36 (33.3%) 10/37 (27%)
    Cardiac disorders
    ATRIAL FIBRILLATION 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 1/36 (2.8%) 3/37 (8.1%)
    PALPITATIONS 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 2/37 (5.4%)
    Ear and labyrinth disorders
    HYPOACUSIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 1/36 (2.8%) 3/37 (8.1%)
    TINNITUS 1/3 (33.3%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    VERTIGO 1/3 (33.3%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 3/37 (8.1%)
    Eye disorders
    CATARACT 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 4/36 (11.1%) 6/37 (16.2%)
    DRY EYE 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 2/37 (5.4%)
    EYE IRRITATION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 3/37 (8.1%)
    OCULAR HYPERAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 3/37 (8.1%)
    VISION BLURRED 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 9/36 (25%) 5/37 (13.5%)
    VISUAL ACUITY REDUCED 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 1/37 (2.7%)
    VITREOUS FLOATERS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 2/37 (5.4%)
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 2/37 (5.4%)
    ABDOMINAL PAIN 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 7/36 (19.4%) 7/37 (18.9%)
    ABDOMINAL PAIN UPPER 0/3 (0%) 0/3 (0%) 0/22 (0%) 5/36 (13.9%) 4/37 (10.8%)
    CONSTIPATION 1/3 (33.3%) 2/3 (66.7%) 11/22 (50%) 18/36 (50%) 19/37 (51.4%)
    DIARRHOEA 1/3 (33.3%) 2/3 (66.7%) 14/22 (63.6%) 24/36 (66.7%) 25/37 (67.6%)
    DIVERTICULAR PERFORATION 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    DRY MOUTH 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 2/37 (5.4%)
    DYSPEPSIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 8/36 (22.2%) 2/37 (5.4%)
    FLATULENCE 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 1/37 (2.7%)
    GASTROINTESTINAL HAEMORRHAGE 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 1/37 (2.7%)
    GASTROINTESTINAL MOTILITY DISORDER 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 0/36 (0%) 0/37 (0%)
    GASTROINTESTINAL PERFORATION 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    GASTROOESOPHAGEAL REFLUX DISEASE 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 4/37 (10.8%)
    HAEMATOCHEZIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 0/37 (0%)
    HAEMORRHOIDS 0/3 (0%) 1/3 (33.3%) 2/22 (9.1%) 2/36 (5.6%) 1/37 (2.7%)
    NAUSEA 0/3 (0%) 3/3 (100%) 11/22 (50%) 18/36 (50%) 17/37 (45.9%)
    PARAESTHESIA ORAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 0/37 (0%)
    STOMATITIS 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 3/36 (8.3%) 1/37 (2.7%)
    TOOTH DISORDER 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    TOOTHACHE 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 3/36 (8.3%) 0/37 (0%)
    VOMITING 0/3 (0%) 0/3 (0%) 6/22 (27.3%) 11/36 (30.6%) 6/37 (16.2%)
    General disorders
    ASTHENIA 0/3 (0%) 1/3 (33.3%) 6/22 (27.3%) 7/36 (19.4%) 12/37 (32.4%)
    CHEST DISCOMFORT 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 1/36 (2.8%) 2/37 (5.4%)
    CHEST PAIN 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 3/37 (8.1%)
    CHILLS 2/3 (66.7%) 2/3 (66.7%) 1/22 (4.5%) 6/36 (16.7%) 2/37 (5.4%)
    FATIGUE 1/3 (33.3%) 2/3 (66.7%) 15/22 (68.2%) 24/36 (66.7%) 18/37 (48.6%)
    FEELING HOT 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    GAIT DISTURBANCE 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 2/37 (5.4%)
    INFLAMMATION 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    INFLUENZA LIKE ILLNESS 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 0/37 (0%)
    IRRITABILITY 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    NON-CARDIAC CHEST PAIN 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 5/36 (13.9%) 2/37 (5.4%)
    OEDEMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 5/36 (13.9%) 1/37 (2.7%)
    OEDEMA PERIPHERAL 0/3 (0%) 1/3 (33.3%) 6/22 (27.3%) 14/36 (38.9%) 9/37 (24.3%)
    PAIN 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 1/36 (2.8%) 5/37 (13.5%)
    PERIPHERAL SWELLING 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 5/36 (13.9%) 7/37 (18.9%)
    PYREXIA 0/3 (0%) 0/3 (0%) 10/22 (45.5%) 14/36 (38.9%) 17/37 (45.9%)
    Hepatobiliary disorders
    HYPERBILIRUBINAEMIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 0/37 (0%)
    Immune system disorders
    DRUG HYPERSENSITIVITY 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    SEASONAL ALLERGY 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 3/36 (8.3%) 0/37 (0%)
    Infections and infestations
    BRONCHITIS 0/3 (0%) 0/3 (0%) 5/22 (22.7%) 8/36 (22.2%) 10/37 (27%)
    CELLULITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 4/36 (11.1%) 4/37 (10.8%)
    CONJUNCTIVITIS 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 1/36 (2.8%) 2/37 (5.4%)
    EAR INFECTION 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    FUNGAL INFECTION 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    GASTROENTERITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 3/37 (8.1%)
    GASTROENTERITIS VIRAL 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 0/37 (0%)
    GINGIVITIS 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 0/37 (0%)
    HERPES ZOSTER 0/3 (0%) 0/3 (0%) 0/22 (0%) 4/36 (11.1%) 0/37 (0%)
    INFLUENZA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 8/36 (22.2%) 3/37 (8.1%)
    LOCALISED INFECTION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 2/37 (5.4%)
    LUNG INFECTION 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 3/37 (8.1%)
    NASOPHARYNGITIS 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 10/36 (27.8%) 9/37 (24.3%)
    ORAL CANDIDIASIS 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 1/36 (2.8%) 5/37 (13.5%)
    ORAL HERPES 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    PHARYNGITIS 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 2/37 (5.4%)
    PNEUMONIA 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 7/36 (19.4%) 9/37 (24.3%)
    PNEUMONIA VIRAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    RHINITIS 1/3 (33.3%) 0/3 (0%) 1/22 (4.5%) 5/36 (13.9%) 8/37 (21.6%)
    SEPSIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 2/37 (5.4%)
    SINUSITIS 1/3 (33.3%) 0/3 (0%) 3/22 (13.6%) 5/36 (13.9%) 3/37 (8.1%)
    UPPER RESPIRATORY TRACT INFECTION 0/3 (0%) 1/3 (33.3%) 7/22 (31.8%) 19/36 (52.8%) 15/37 (40.5%)
    UPPER RESPIRATORY TRACT INFECTION BACTERIAL 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    URINARY TRACT INFECTION 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 6/36 (16.7%) 5/37 (13.5%)
    VIRAL INFECTION 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    VIRAL UPPER RESPIRATORY TRACT INFECTION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 2/37 (5.4%)
    Injury, poisoning and procedural complications
    ARTHROPOD BITE 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    CONTUSION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 4/37 (10.8%)
    FALL 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 5/36 (13.9%) 4/37 (10.8%)
    JOINT DISLOCATION 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    LIGAMENT SPRAIN 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    SKIN ABRASION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 2/37 (5.4%)
    STOMA SITE PAIN 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    SUNBURN 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 0/37 (0%)
    Investigations
    ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    ALANINE AMINOTRANSFERASE INCREASED 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 5/36 (13.9%) 4/37 (10.8%)
    ASPARTATE AMINOTRANSFERASE INCREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 4/37 (10.8%)
    BLOOD ALKALINE PHOSPHATASE INCREASED 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 3/36 (8.3%) 1/37 (2.7%)
    BLOOD BICARBONATE DECREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 7/36 (19.4%) 4/37 (10.8%)
    BLOOD CREATININE INCREASED 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 5/36 (13.9%) 4/37 (10.8%)
    BLOOD LACTATE DEHYDROGENASE INCREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 4/36 (11.1%) 1/37 (2.7%)
    BLOOD MAGNESIUM DECREASED 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 0/37 (0%)
    BLOOD PHOSPHORUS DECREASED 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    BLOOD POTASSIUM DECREASED 0/3 (0%) 1/3 (33.3%) 1/22 (4.5%) 0/36 (0%) 0/37 (0%)
    BLOOD UREA INCREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 2/37 (5.4%)
    CARDIAC MURMUR 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 1/37 (2.7%)
    EJECTION FRACTION DECREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    IMMUNOGLOBULINS DECREASED 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    INTERNATIONAL NORMALISED RATIO INCREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 1/37 (2.7%)
    NEUTROPHIL COUNT INCREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 1/37 (2.7%)
    PROTEIN TOTAL INCREASED 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    PROTHROMBIN TIME PROLONGED 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    WEIGHT DECREASED 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 7/36 (19.4%) 4/37 (10.8%)
    WEIGHT INCREASED 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 3/37 (8.1%)
    WHITE BLOOD CELL COUNT DECREASED 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 2/37 (5.4%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 10/36 (27.8%) 8/37 (21.6%)
    DEHYDRATION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 2/37 (5.4%)
    DIABETES MELLITUS 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 2/37 (5.4%)
    GOUT 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 2/37 (5.4%)
    HYPERCALCAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 3/37 (8.1%)
    HYPERGLYCAEMIA 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 9/36 (25%) 12/37 (32.4%)
    HYPERKALAEMIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 1/37 (2.7%)
    HYPERNATRAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 0/37 (0%)
    HYPOALBUMINAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 5/36 (13.9%) 3/37 (8.1%)
    HYPOCALCAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 3/37 (8.1%)
    HYPOKALAEMIA 0/3 (0%) 1/3 (33.3%) 6/22 (27.3%) 7/36 (19.4%) 7/37 (18.9%)
    HYPOMAGNESAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 2/37 (5.4%)
    HYPONATRAEMIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 2/37 (5.4%)
    HYPOPHOSPHATAEMIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 5/37 (13.5%)
    METABOLIC ACIDOSIS 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    VITAMIN D DEFICIENCY 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 3/37 (8.1%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/3 (0%) 2/3 (66.7%) 7/22 (31.8%) 12/36 (33.3%) 8/37 (21.6%)
    BACK PAIN 0/3 (0%) 1/3 (33.3%) 7/22 (31.8%) 17/36 (47.2%) 14/37 (37.8%)
    BONE PAIN 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 4/36 (11.1%) 8/37 (21.6%)
    MUSCLE SPASMS 1/3 (33.3%) 1/3 (33.3%) 10/22 (45.5%) 22/36 (61.1%) 23/37 (62.2%)
    MUSCULAR WEAKNESS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 1/37 (2.7%)
    MUSCULOSKELETAL CHEST PAIN 0/3 (0%) 0/3 (0%) 5/22 (22.7%) 4/36 (11.1%) 3/37 (8.1%)
    MUSCULOSKELETAL DISCOMFORT 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    MUSCULOSKELETAL PAIN 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 6/36 (16.7%) 4/37 (10.8%)
    MUSCULOSKELETAL STIFFNESS 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    MYALGIA 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 6/36 (16.7%) 1/37 (2.7%)
    NECK PAIN 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 3/37 (8.1%)
    OSTEONECROSIS OF JAW 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    PAIN IN EXTREMITY 0/3 (0%) 1/3 (33.3%) 5/22 (22.7%) 10/36 (27.8%) 13/37 (35.1%)
    PAIN IN JAW 1/3 (33.3%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 1/37 (2.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 2/37 (5.4%)
    Nervous system disorders
    AMNESIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 0/36 (0%) 2/37 (5.4%)
    BALANCE DISORDER 1/3 (33.3%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 1/37 (2.7%)
    CARPAL TUNNEL SYNDROME 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 0/36 (0%) 0/37 (0%)
    DISTURBANCE IN ATTENTION 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 0/36 (0%) 0/37 (0%)
    DIZZINESS 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 12/36 (33.3%) 7/37 (18.9%)
    DYSGEUSIA 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 9/36 (25%) 6/37 (16.2%)
    HEADACHE 1/3 (33.3%) 0/3 (0%) 5/22 (22.7%) 14/36 (38.9%) 7/37 (18.9%)
    HYPOAESTHESIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 5/36 (13.9%) 3/37 (8.1%)
    HYPOGEUSIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    MEMORY IMPAIRMENT 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 2/37 (5.4%)
    NEURALGIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    NEUROPATHY PERIPHERAL 0/3 (0%) 0/3 (0%) 7/22 (31.8%) 8/36 (22.2%) 7/37 (18.9%)
    PARAESTHESIA 1/3 (33.3%) 0/3 (0%) 3/22 (13.6%) 6/36 (16.7%) 3/37 (8.1%)
    PERIPHERAL SENSORY NEUROPATHY 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 5/37 (13.5%)
    PSYCHOMOTOR HYPERACTIVITY 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 0/37 (0%)
    SCIATICA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    SINUS HEADACHE 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 1/37 (2.7%)
    SOMNOLENCE 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    SYNCOPE 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 6/36 (16.7%) 1/37 (2.7%)
    TREMOR 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 5/37 (13.5%)
    Psychiatric disorders
    AGGRESSION 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    ANXIETY 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 5/36 (13.9%) 1/37 (2.7%)
    CONFUSIONAL STATE 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 3/37 (8.1%)
    DEPRESSED MOOD 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 1/37 (2.7%)
    DEPRESSION 1/3 (33.3%) 0/3 (0%) 2/22 (9.1%) 4/36 (11.1%) 3/37 (8.1%)
    INSOMNIA 2/3 (66.7%) 1/3 (33.3%) 7/22 (31.8%) 10/36 (27.8%) 15/37 (40.5%)
    MOOD SWINGS 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 2/37 (5.4%)
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 1/36 (2.8%) 0/37 (0%)
    DYSURIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 2/37 (5.4%)
    HAEMATURIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 2/37 (5.4%)
    POLLAKIURIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    RENAL FAILURE 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 2/37 (5.4%)
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 3/37 (8.1%)
    VULVOVAGINAL PRURITUS 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    Respiratory, thoracic and mediastinal disorders
    ASTHMA 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    COUGH 0/3 (0%) 0/3 (0%) 7/22 (31.8%) 12/36 (33.3%) 13/37 (35.1%)
    DYSPHONIA 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 6/36 (16.7%) 3/37 (8.1%)
    DYSPNOEA 0/3 (0%) 0/3 (0%) 5/22 (22.7%) 11/36 (30.6%) 10/37 (27%)
    DYSPNOEA EXERTIONAL 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 9/36 (25%) 5/37 (13.5%)
    EPISTAXIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 6/36 (16.7%) 6/37 (16.2%)
    HICCUPS 0/3 (0%) 0/3 (0%) 0/22 (0%) 1/36 (2.8%) 3/37 (8.1%)
    LUNG DISORDER 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 2/37 (5.4%)
    NASAL CONGESTION 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 5/37 (13.5%)
    OROPHARYNGEAL PAIN 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 5/36 (13.9%) 4/37 (10.8%)
    PARANASAL SINUS HYPERSECRETION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 1/37 (2.7%)
    PRODUCTIVE COUGH 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 5/36 (13.9%) 2/37 (5.4%)
    PULMONARY EMBOLISM 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 2/37 (5.4%)
    RALES 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    RHINORRHOEA 0/3 (0%) 0/3 (0%) 4/22 (18.2%) 4/36 (11.1%) 5/37 (13.5%)
    SINUS CONGESTION 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 2/37 (5.4%)
    THROAT IRRITATION 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 0/36 (0%) 1/37 (2.7%)
    UPPER-AIRWAY COUGH SYNDROME 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 1/37 (2.7%)
    Skin and subcutaneous tissue disorders
    ALOPECIA 0/3 (0%) 0/3 (0%) 0/22 (0%) 3/36 (8.3%) 0/37 (0%)
    BLISTER 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    DRY SKIN 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 1/37 (2.7%)
    ECCHYMOSIS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 3/36 (8.3%) 3/37 (8.1%)
    ERYTHEMA 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 3/36 (8.3%) 4/37 (10.8%)
    HYPERHIDROSIS 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 4/36 (11.1%) 5/37 (13.5%)
    INGROWING NAIL 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 0/36 (0%) 0/37 (0%)
    NIGHT SWEATS 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 8/36 (22.2%) 10/37 (27%)
    PRURITUS 1/3 (33.3%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 2/37 (5.4%)
    RASH 1/3 (33.3%) 1/3 (33.3%) 3/22 (13.6%) 9/36 (25%) 9/37 (24.3%)
    RASH GENERALISED 1/3 (33.3%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 2/37 (5.4%)
    RASH MACULAR 0/3 (0%) 1/3 (33.3%) 0/22 (0%) 0/36 (0%) 0/37 (0%)
    RASH MACULO-PAPULAR 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 2/36 (5.6%) 1/37 (2.7%)
    SCAB 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    SKIN DISCOLOURATION 0/3 (0%) 0/3 (0%) 0/22 (0%) 0/36 (0%) 2/37 (5.4%)
    SKIN LESION 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 0/36 (0%) 1/37 (2.7%)
    URTICARIA 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 1/36 (2.8%) 0/37 (0%)
    Vascular disorders
    DEEP VEIN THROMBOSIS 1/3 (33.3%) 0/3 (0%) 3/22 (13.6%) 2/36 (5.6%) 2/37 (5.4%)
    FLUSHING 0/3 (0%) 0/3 (0%) 1/22 (4.5%) 4/36 (11.1%) 2/37 (5.4%)
    HOT FLUSH 0/3 (0%) 1/3 (33.3%) 2/22 (9.1%) 2/36 (5.6%) 2/37 (5.4%)
    HYPERTENSION 0/3 (0%) 0/3 (0%) 2/22 (9.1%) 2/36 (5.6%) 2/37 (5.4%)
    HYPOTENSION 0/3 (0%) 0/3 (0%) 3/22 (13.6%) 4/36 (11.1%) 4/37 (10.8%)
    PHLEBITIS SUPERFICIAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)
    THROMBOPHLEBITIS SUPERFICIAL 0/3 (0%) 0/3 (0%) 0/22 (0%) 2/36 (5.6%) 0/37 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.

    Results Point of Contact

    Name/Title Global Medical Services
    Organization AbbVie
    Phone 800-633-9110
    Email
    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT00742560
    Other Study ID Numbers:
    • HuLuc63-1703
    • 2007-006677-83
    First Posted:
    Aug 27, 2008
    Last Update Posted:
    Jan 10, 2018
    Last Verified:
    Jan 1, 2018