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CC-4047 and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Amyloidosis

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT00558896
Collaborator
National Cancer Institute (NCI) (NIH)
378
Enrollment
3
Locations
7
Arms
119.8
Actual Duration (Months)
126
Patients Per Site
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. Dexamethasone and CC-4047 may stop the growth of cancer cells by blocking blood flow to the cancer. Giving CC-4047 together with dexamethasone may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving CC-4047 together with dexamethasone works in treating patients with relapsed or refractory multiple myeloma or amyloidosis.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES:

  • To assess the response rate and duration of remission with low-dose CC-4047 plus dexamethasone in patients with relapsed or refractory multiple myeloma or amyloidosis.

  • To assess the toxicity of CC-4047 plus dexamethasone in this patient population.

  • To assess in an expansion cohort the response rate with an increase in CC-4047 dose among patients who fail to respond adequately to the initial starting dose following the first 2 courses of treatment.

  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with lenalidomide resistant or refractory multiple myeloma.

  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with previously treated light chain amyloidosis.

  • To assess the response rate and duration of remission with low- and high-dose CC-4047 plus dexamethasone in patients with lenalidomide and bortezomib refractory multiple myeloma.

  • To assess the response rate and duration of remission with high-dose CC-4047 plus dexamethasone in patients with relapsed or refractory myeloma who received ≤ 3 treatment regimens.

OUTLINE: Patients are grouped according to disease status (relapsed/refractory myeloma [closed to accrual as of 8/5/2008] vs lenalidomide resistant/refractory myeloma [closed to accrual as of 4/2/2009] vs previously treated light chain amyloidosis vs lenalidomide and bortezomib resistant/refractory myeloma {low-dose/day}[closed to accrual as of 11/20/09] vs lenalidomide and bortezomib resistant/refractory myeloma (high-dose/day) vs relapsed/refractory myeloma {high-dose/day}).

Patients receive oral CC-4047 on days 1-28 and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks and then at 6 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
378 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of CC-4047 Plus Dexamethasone in Patients With Relapsed of Refractory Multiple Myeloma or Amyloidosis
Actual Study Start Date :
Nov 1, 2007
Actual Primary Completion Date :
Sep 1, 2012
Actual Study Completion Date :
Oct 25, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Relapsed Myeloma (<4 Prior Regimens)

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Names:
  • CC-4047

    		•
    Experimental: Lenalidomide Refractory Myeloma

    Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

    Drug: dexamethasone
    40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

    Drug: pomalidomide
    2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
    Other Names:
  • CC-4047

    		•
    Experimental: Bortezomib/Lenalidomide Refractory/Relapsed Myeloma

    Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

    Drug: dexamethasone
    40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

    Drug: pomalidomide
    2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
    Other Names:
  • CC-4047

    		•
    Experimental: Bortezomib/Lenalidomide Relapsed/Refractory Myeloma

    Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

    Drug: dexamethasone
    40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

    Drug: pomalidomide
    2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
    Other Names:
  • CC-4047

    		•
    Experimental: Relapsed Myeloma (< 4 Prior Regimens)

    Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

    Drug: dexamethasone
    40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

    Drug: pomalidomide
    2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
    Other Names:
  • CC-4047

    		•
    Experimental: Relapsed/Refractory Myeloma

    Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

    Drug: dexamethasone
    40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

    Drug: pomalidomide
    2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
    Other Names:
  • CC-4047

    		•
    Experimental: Relapsed Amyloidosis

    Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

    Drug: dexamethasone
    40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

    Drug: pomalidomide
    2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
    Other Names:
  • CC-4047

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response) [Duration of study (up to 3 years)]

      Response that was confirmed on 2 consecutive evaluations Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow. Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow. Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [Duration of study (up to 5 years)]

      PFS was defined as the time from registration to progression or death due to any cause. PFS was analyzed using Kaplan Meier method. Progression was defined as any one or more of the following: 25% increase in serum M-component (absolute increase >= 0.5g/dl) 25% increase in urine M-component (absolute increase >= 200mg/24hour 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl) 25% increase in bone marrow plasma cell percentage (absolute increase of >=10%) Definite development of new bone lesion or soft tissue plasmacytomas

    2. Duration of Response [Duration of study (up to 5 years)]

      Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. Kaplan Meier method was used to compute this outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 120 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    DISEASE CHARACTERISTICS:

    • Symptomatic multiple myeloma

    • Previously treated disease meeting one of the following criteria:

    • Have light-chain amyloidosis that has been treated with at least one prior regimen

    • Symptomatic (relapsed or refractory) multiple myeloma

    • Patients must have received 1-3 treatment regimens

    • Induction therapy followed by autologous stem cell transplantation and consolidation considered one regimen

    • Measurable disease, as defined by 1 of the following:

    • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis

    • More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis

    • Serum immunoglobulin free light chain (FLC) > 10 mg/dL and an abnormal FLC ratio

    • Measurable soft tissue plasmacytoma, not previously irradiated

    • More than 30% plasma cells in bone marrow

    • At least 10% plasma cells as measured by bone marrow aspirate, bone marrow biopsy, or labeling index

    • No monoclonal gammopathy of undetermined significance (not applicable for patients with amyloid)

    • No smoldering myeloma (not applicable for patients with amyloid)

    PATIENT CHARACTERISTICS:

    • ECOG performance status 0, 1, or 2

    • ANC ≥ 1,000/μL

    • Platelet count ≥ 75,000/μL

    • Creatinine ≤ 2.5 mg/dL

    • Not pregnant or nursing

    • Women must refrain from breastfeeding during study participation and for at least 28 days after discontinuation of study drug

    • Negative pregnancy test

    • Fertile female patients must use two reliable forms of contraception simultaneously at least 28 days before beginning, during, and at least 28 days after completion of study drug

    • The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, or cervical cap)

    • Fertile male patients must use a latex condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment

    • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug

    • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug

    • No uncontrolled infection

    • No other active malignancy

    • No New York Heart Association class III or IV cardiac disease (all patients)

    • Serum troponin T > 0.10 ng/mL (amyloid patients only)

    • No known positivity for HIV or active hepatitis infection

    • No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated

    • No condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk for participating in the study or confounds the ability to interpret data from the study

    • No known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash

    • No peripheral neuropathy > grade 2

    PRIOR CONCURRENT THERAPY:

    • All previous cancer therapy, including chemotherapy and investigational agents, must have been discontinued ≥ 2 weeks prior to study registration

    • No radiotherapy ≤ 14 days prior to study registration

    • No other concurrent anti-myeloma therapy

    • No concurrent radiotherapy, except for palliation of a single painful bone lesion or fracture

    • Routine concurrent bisphosphonate therapy allowed for patients with myeloma bone disease

    • Willing and able to take aspirin or alternate prophylactic anticoagulation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Arizona Scottsdale Arizona United States 85259-5499
    2 Mayo Clinic in Florida Jacksonville Florida United States 32224
    3 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Martha Q. Lacy, MD, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT00558896
    Other Study ID Numbers:
    • CDR0000574742
    • P30CA015083
    • 07-003064
    • NCI-2009-01283
    • MC0789
    • NCT01219634
    First Posted:
    Nov 15, 2007
    Last Update Posted:
    Apr 18, 2018
    Last Verified:
    Mar 1, 2018
    Keywords provided by Mayo Clinic
    stage II multiple myeloma
    stage III multiple myeloma
    refractory multiple myeloma
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Plasmacytoma
    Amyloidosis
    Dexamethasone
    Pomalidomide

    Study Results

    Participant Flow

    Recruitment Details Between November 2007 and March 2012, 7 sequential phase 2 trials (reported as separate arms) were conducted. A total of 378 participants were recruited at Mayo Clinic (Arizona, Florida or Arizona).
    Pre-assignment Detail One patient was deemed ineligible and excluded from all analyses.
    Arm/Group Title Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Arm/Group Description Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle
    Period Title: Overall Study
    STARTED 60 34 35 35 60 120 33
    COMPLETED 39 27 30 23 37 68 9
    NOT COMPLETED 21 7 5 12 23 52 24

    Baseline Characteristics

    Arm/Group Title Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose Total
    Arm/Group Description Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Total of all reporting groups
    Overall Participants 60 34 35 35 60 120 33 377
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    65.5
    61.5
    62
    61
    65.5
    65
    66
    64
    Sex: Female, Male (Count of Participants)
    Female
    24
    40%
    11
    32.4%
    8
    22.9%
    14
    40%
    20
    33.3%
    47
    39.2%
    14
    42.4%
    138
    36.6%
    Male
    36
    60%
    23
    67.6%
    27
    77.1%
    21
    60%
    40
    66.7%
    73
    60.8%
    19
    57.6%
    239
    63.4%
    Region of Enrollment (participants) [Number]
    United States
    60
    100%
    34
    100%
    35
    100%
    35
    100%
    60
    100%
    120
    100%
    33
    100%
    377
    100%

    Outcome Measures

    1. Primary Outcome
    Title The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response)
    Description Response that was confirmed on 2 consecutive evaluations Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow. Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow. Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.
    Time Frame Duration of study (up to 3 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Arm/Group Description Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle
    Measure Participants 60 34 35 35 60 120 33
    Number [participants]
    39
    65%
    11
    32.4%
    9
    25.7%
    10
    28.6%
    23
    38.3%
    25
    20.8%
    16
    48.5%
    2. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description PFS was defined as the time from registration to progression or death due to any cause. PFS was analyzed using Kaplan Meier method. Progression was defined as any one or more of the following: 25% increase in serum M-component (absolute increase >= 0.5g/dl) 25% increase in urine M-component (absolute increase >= 200mg/24hour 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl) 25% increase in bone marrow plasma cell percentage (absolute increase of >=10%) Definite development of new bone lesion or soft tissue plasmacytomas
    Time Frame Duration of study (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Arm/Group Description Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle
    Measure Participants 60 34 35 35 60 120 33
    Median (95% Confidence Interval) [months]
    13
    5
    6.4
    3.3
    7.7
    4.3
    14.1
    3. Secondary Outcome
    Title Duration of Response
    Description Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. Kaplan Meier method was used to compute this outcome.
    Time Frame Duration of study (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    Participants who achieved a partial response(PR) or better were evaluable for this analysis.
    Arm/Group Title Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Arm/Group Description Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle
    Measure Participants 39 11 9 10 23 25 16
    Median (95% Confidence Interval) [months]
    21.3
    8.2
    15.6
    3.1
    NA
    8.3
    19

    Adverse Events

    Time Frame
    Adverse Event Reporting Description One participant in the Relapse/Refractory Myeloma: High Dose group refused prior to starting treatment, thus was not included in the adverse event analysis.
    Arm/Group Title Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Arm/Group Description Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle
    All Cause Mortality
    Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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) / (NaN) / (NaN)
    Serious Adverse Events
    Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 22/60 (36.7%) 11/34 (32.4%) 15/35 (42.9%) 11/35 (31.4%) 21/60 (35%) 32/119 (26.9%) 18/33 (54.5%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 2/35 (5.7%) 2 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Hemoglobin decreased 1/60 (1.7%) 1 0/34 (0%) 0 5/35 (14.3%) 5 2/35 (5.7%) 2 2/60 (3.3%) 2 5/119 (4.2%) 5 1/33 (3%) 1
    Cardiac disorders
    Atrial fibrillation 2/60 (3.3%) 3 0/34 (0%) 0 3/35 (8.6%) 3 0/35 (0%) 0 0/60 (0%) 0 2/119 (1.7%) 2 2/33 (6.1%) 2
    Atrial flutter 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Cardiac disorder 1/60 (1.7%) 1 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Cardiac valve disease 1/60 (1.7%) 1 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Left ventricular dysfunction 1/60 (1.7%) 1 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Left ventricular failure 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Pericardial effusion 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Restrictive cardiomyopathy 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Sinus bradycardia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Eye disorders
    Cataract 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Eye disorder 1/60 (1.7%) 2 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Gastrointestinal disorders
    Cecum perforation 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Colitis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Colonic perforation 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Diarrhea 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Esophagitis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    General disorders
    Chest pain 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Death 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 2/33 (6.1%) 2
    Disease progression 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Fatigue 0/60 (0%) 0 3/34 (8.8%) 3 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Fever 1/60 (1.7%) 1 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 1/60 (1.7%) 1 1/119 (0.8%) 1 0/33 (0%) 0
    Multi-organ failure 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Pain 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 2/33 (6.1%) 2
    Hepatobiliary disorders
    Hepatic failure 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Infections and infestations
    Bladder infection 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Bone infection 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Bronchitis 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Infection 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Infectious meningitis 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Kidney infection 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Pneumonia 8/60 (13.3%) 10 6/34 (17.6%) 7 8/35 (22.9%) 9 1/35 (2.9%) 2 7/60 (11.7%) 7 13/119 (10.9%) 13 6/33 (18.2%) 9
    Sepsis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Sinusitis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 1/33 (3%) 1
    Skin infection 2/60 (3.3%) 2 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Upper respiratory infection 1/60 (1.7%) 1 1/34 (2.9%) 1 2/35 (5.7%) 2 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 1/33 (3%) 1
    Injury, poisoning and procedural complications
    Fracture 2/60 (3.3%) 2 0/34 (0%) 0 2/35 (5.7%) 2 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Intraoperative musculoskeletal injury - Joint 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Aspartate aminotransferase increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Bilirubin increased 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Creatinine increased 2/60 (3.3%) 2 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Electrocardiogram QTc interval prolonged 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    INR increased 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Leukocyte count decreased 0/60 (0%) 0 0/34 (0%) 0 4/35 (11.4%) 4 3/35 (8.6%) 3 4/60 (6.7%) 4 5/119 (4.2%) 5 1/33 (3%) 1
    Lymphocyte count decreased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 2/60 (3.3%) 2 0/119 (0%) 0 0/33 (0%) 0
    Neutrophil count decreased 1/60 (1.7%) 1 1/34 (2.9%) 1 3/35 (8.6%) 3 4/35 (11.4%) 5 6/60 (10%) 6 5/119 (4.2%) 5 2/33 (6.1%) 2
    Platelet count decreased 3/60 (5%) 4 0/34 (0%) 0 2/35 (5.7%) 3 3/35 (8.6%) 3 4/60 (6.7%) 4 6/119 (5%) 6 2/33 (6.1%) 2
    Metabolism and nutrition disorders
    Acidosis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Blood glucose increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Blood uric acid increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Dehydration 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 1/60 (1.7%) 1 1/119 (0.8%) 1 0/33 (0%) 0
    Serum calcium increased 1/60 (1.7%) 1 2/34 (5.9%) 2 1/35 (2.9%) 1 1/35 (2.9%) 1 0/60 (0%) 0 2/119 (1.7%) 2 0/33 (0%) 0
    Serum potassium increased 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Serum sodium decreased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Bone pain 1/60 (1.7%) 2 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 2/60 (3.3%) 2 0/119 (0%) 0 0/33 (0%) 0
    Muscle weakness 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Musculoskeletal disorder 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Treatment related secondary malignancy 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Tumor pain 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Nervous system disorders
    Dizziness 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Encephalopathy 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Ischemia cerebrovascular 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 1/119 (0.8%) 1 0/33 (0%) 0
    Peripheral motor neuropathy 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Peripheral sensory neuropathy 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 1/33 (3%) 1
    Syncope 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Psychiatric disorders
    Confusion 2/60 (3.3%) 2 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Depression 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Renal and urinary disorders
    Renal failure 0/60 (0%) 0 0/34 (0%) 0 4/35 (11.4%) 4 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Urethral obstruction 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Reproductive system and breast disorders
    Scrotal pain 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Dyspnea 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 1/119 (0.8%) 1 1/33 (3%) 2
    Hemorrhage nasal 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Hypoxia 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Pleural effusion 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Pneumonitis 0/60 (0%) 0 1/34 (2.9%) 1 1/35 (2.9%) 1 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Respiratory disorder 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Vascular disorders
    Hematoma 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Hypotension 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Thrombosis 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Other (Not Including Serious) Adverse Events
    Relapsed Myeloma (<4 Prior Regimens): Low Dose Lenalidomide Refractory Myeloma: Low Dose Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose Relapsed Myeloma (< 4 Prior Regimens): High Dose Relapsed/Refractory Myeloma: High Dose Relapsed Amyloidosis: Low Dose
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 60/60 (100%) 34/34 (100%) 34/35 (97.1%) 35/35 (100%) 60/60 (100%) 119/119 (100%) 32/33 (97%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 2/35 (5.7%) 2 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 2
    Hemoglobin decreased 57/60 (95%) 707 34/34 (100%) 241 34/35 (97.1%) 239 34/35 (97.1%) 134 55/60 (91.7%) 348 115/119 (96.6%) 418 31/33 (93.9%) 277
    Cardiac disorders
    Atrial fibrillation 2/60 (3.3%) 3 0/34 (0%) 0 3/35 (8.6%) 7 0/35 (0%) 0 2/60 (3.3%) 11 2/119 (1.7%) 2 3/33 (9.1%) 5
    Atrial flutter 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Atrial tachycardia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 3
    Cardiac disorder 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Cardiac pain 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Myocardial ischemia 0/60 (0%) 0 1/34 (2.9%) 1 1/35 (2.9%) 1 1/35 (2.9%) 2 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Palpitations 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 2 0/119 (0%) 0 0/33 (0%) 0
    Premature ventricular contractions 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Restrictive cardiomyopathy 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Sinus bradycardia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 2/60 (3.3%) 2 0/119 (0%) 0 0/33 (0%) 0
    Ear and labyrinth disorders
    Tinnitus 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Endocrine disorders
    Hypothyroidism 2/60 (3.3%) 2 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Eye disorders
    Cataract 2/60 (3.3%) 6 1/34 (2.9%) 1 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 2 0/33 (0%) 0
    Diplopia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Dry eye syndrome 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Extraocular muscle paresis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Eye disorder 1/60 (1.7%) 10 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Eye pain 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Night blindness 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 2 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Retinal detachment 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Vision blurred 2/60 (3.3%) 2 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 2 0/119 (0%) 0 3/33 (9.1%) 6
    Vitreous hemorrhage 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Gastrointestinal disorders
    Abdominal pain 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 2 0/35 (0%) 0 1/60 (1.7%) 3 0/119 (0%) 0 0/33 (0%) 0
    Ascites 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 2
    Colitis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Constipation 11/60 (18.3%) 20 1/34 (2.9%) 1 1/35 (2.9%) 1 0/35 (0%) 0 4/60 (6.7%) 12 3/119 (2.5%) 3 3/33 (9.1%) 6
    Diarrhea 26/60 (43.3%) 71 11/34 (32.4%) 57 11/35 (31.4%) 47 8/35 (22.9%) 18 23/60 (38.3%) 73 30/119 (25.2%) 49 16/33 (48.5%) 44
    Dyspepsia 2/60 (3.3%) 2 0/34 (0%) 0 0/35 (0%) 0 2/35 (5.7%) 3 3/60 (5%) 8 1/119 (0.8%) 1 2/33 (6.1%) 4
    Dysphagia 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Ear, nose and throat examination abnormal 0/60 (0%) 0 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Enteritis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Gastritis 1/60 (1.7%) 1 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Gastrointestinal disorder 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 2/60 (3.3%) 3 0/119 (0%) 0 0/33 (0%) 0
    Mucositis oral 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Nausea 19/60 (31.7%) 38 10/34 (29.4%) 37 11/35 (31.4%) 46 7/35 (20%) 10 13/60 (21.7%) 37 31/119 (26.1%) 43 13/33 (39.4%) 32
    Oral hemorrhage 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Rectal hemorrhage 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Toothache 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Vomiting 10/60 (16.7%) 16 6/34 (17.6%) 8 7/35 (20%) 28 4/35 (11.4%) 4 6/60 (10%) 7 7/119 (5.9%) 8 5/33 (15.2%) 7
    General disorders
    Disease progression 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 1/119 (0.8%) 1 1/33 (3%) 1
    Edema limbs 9/60 (15%) 19 4/34 (11.8%) 9 1/35 (2.9%) 9 1/35 (2.9%) 1 4/60 (6.7%) 14 1/119 (0.8%) 3 7/33 (21.2%) 12
    Fatigue 56/60 (93.3%) 718 32/34 (94.1%) 278 31/35 (88.6%) 247 32/35 (91.4%) 127 56/60 (93.3%) 440 111/119 (93.3%) 372 32/33 (97%) 331
    Fever 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 2/60 (3.3%) 2 0/119 (0%) 0 0/33 (0%) 0
    Irritability 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Localized edema 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 3
    Pain 1/60 (1.7%) 1 3/34 (8.8%) 3 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Immune system disorders
    Hypersensitivity 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Infections and infestations
    Abdominal infection 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Appendicitis 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Bladder infection 0/60 (0%) 0 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Bone infection 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Bronchitis 0/60 (0%) 0 2/34 (5.9%) 2 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 1/119 (0.8%) 1 3/33 (9.1%) 4
    Gingival infection 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 3 0/33 (0%) 0
    Infection 2/60 (3.3%) 3 2/34 (5.9%) 2 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Mucosal infection 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Pneumonia 7/60 (11.7%) 8 3/34 (8.8%) 3 4/35 (11.4%) 6 2/35 (5.7%) 2 6/60 (10%) 6 7/119 (5.9%) 8 3/33 (9.1%) 4
    Sepsis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Sinusitis 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 2/119 (1.7%) 2 1/33 (3%) 1
    Skin infection 0/60 (0%) 0 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 1/33 (3%) 1
    Tooth infection 0/60 (0%) 0 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Upper aerodigestive tract infection 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Upper respiratory infection 6/60 (10%) 7 5/34 (14.7%) 6 1/35 (2.9%) 1 0/35 (0%) 0 3/60 (5%) 6 2/119 (1.7%) 2 2/33 (6.1%) 3
    Urinary tract infection 1/60 (1.7%) 1 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 1/60 (1.7%) 1 1/119 (0.8%) 2 0/33 (0%) 0
    Injury, poisoning and procedural complications
    Bruising 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 2
    Fracture 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Intraoperative ocular injury 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Investigations
    Alanine aminotransferase increased 1/60 (1.7%) 4 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 3/60 (5%) 3 2/119 (1.7%) 2 1/33 (3%) 1
    Alkaline phosphatase increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 2/33 (6.1%) 4
    Aspartate aminotransferase increased 1/60 (1.7%) 2 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 3/119 (2.5%) 3 0/33 (0%) 0
    Bilirubin increased 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 3 0/35 (0%) 0 1/60 (1.7%) 4 1/119 (0.8%) 1 1/33 (3%) 1
    Cardiac troponin I increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Creatine phosphokinase increased 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Creatinine increased 2/60 (3.3%) 2 1/34 (2.9%) 1 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 3/119 (2.5%) 3 1/33 (3%) 3
    Electrocardiogram QTc interval prolonged 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    INR increased 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 3 2/33 (6.1%) 2
    Leukocyte count decreased 44/60 (73.3%) 243 27/34 (79.4%) 92 29/35 (82.9%) 147 31/35 (88.6%) 122 54/60 (90%) 266 103/119 (86.6%) 303 22/33 (66.7%) 96
    Lymphocyte count decreased 6/60 (10%) 69 4/34 (11.8%) 10 12/35 (34.3%) 48 14/35 (40%) 41 32/60 (53.3%) 130 8/119 (6.7%) 22 3/33 (9.1%) 11
    Neutrophil count decreased 48/60 (80%) 419 26/34 (76.5%) 113 29/35 (82.9%) 132 30/35 (85.7%) 106 51/60 (85%) 304 98/119 (82.4%) 284 21/33 (63.6%) 90
    Platelet count decreased 31/60 (51.7%) 186 18/34 (52.9%) 87 30/35 (85.7%) 137 30/35 (85.7%) 74 43/60 (71.7%) 152 98/119 (82.4%) 262 19/33 (57.6%) 93
    Weight gain 3/60 (5%) 3 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Weight loss 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Metabolism and nutrition disorders
    Anorexia 20/60 (33.3%) 44 16/34 (47.1%) 23 10/35 (28.6%) 22 12/35 (34.3%) 15 18/60 (30%) 50 46/119 (38.7%) 70 12/33 (36.4%) 37
    Blood glucose increased 14/60 (23.3%) 29 5/34 (14.7%) 19 4/35 (11.4%) 12 2/35 (5.7%) 2 16/60 (26.7%) 58 10/119 (8.4%) 14 1/33 (3%) 1
    Blood uric acid increased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 2
    Dehydration 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Glucose intolerance 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Serum albumin decreased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Serum calcium decreased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Serum calcium increased 0/60 (0%) 0 2/34 (5.9%) 2 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 2/119 (1.7%) 2 0/33 (0%) 0
    Serum phosphate decreased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 2/119 (1.7%) 2 0/33 (0%) 0
    Serum potassium decreased 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 1/33 (3%) 1
    Serum potassium increased 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Serum sodium decreased 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 3/119 (2.5%) 3 3/33 (9.1%) 4
    Musculoskeletal and connective tissue disorders
    Arthritis 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Back pain 6/60 (10%) 7 3/34 (8.8%) 3 1/35 (2.9%) 1 3/35 (8.6%) 4 0/60 (0%) 0 3/119 (2.5%) 5 0/33 (0%) 0
    Bone pain 1/60 (1.7%) 1 3/34 (8.8%) 3 2/35 (5.7%) 3 1/35 (2.9%) 4 0/60 (0%) 0 2/119 (1.7%) 2 0/33 (0%) 0
    Joint pain 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Muscle weakness 4/60 (6.7%) 5 2/34 (5.9%) 4 0/35 (0%) 0 1/35 (2.9%) 1 1/60 (1.7%) 2 1/119 (0.8%) 1 3/33 (9.1%) 4
    Muscle weakness lower limb 4/60 (6.7%) 7 3/34 (8.8%) 4 1/35 (2.9%) 3 0/35 (0%) 0 0/60 (0%) 0 2/119 (1.7%) 7 2/33 (6.1%) 4
    Musculoskeletal disorder 2/60 (3.3%) 5 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 2 0/33 (0%) 0
    Myalgia 3/60 (5%) 3 1/34 (2.9%) 1 0/35 (0%) 0 1/35 (2.9%) 2 3/60 (5%) 6 1/119 (0.8%) 3 1/33 (3%) 5
    Neck pain 0/60 (0%) 0 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Osteoporosis 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 14 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Soft tissue necrosis lower limb 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplasia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Treatment related secondary malignancy 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 2/60 (3.3%) 9 1/119 (0.8%) 1 0/33 (0%) 0
    Nervous system disorders
    Ataxia 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Depressed level of consciousness 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Dizziness 3/60 (5%) 5 0/34 (0%) 0 2/35 (5.7%) 2 0/35 (0%) 0 5/60 (8.3%) 6 2/119 (1.7%) 2 1/33 (3%) 1
    Headache 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 1/35 (2.9%) 1 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Memory impairment 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 1/33 (3%) 1
    Myelitis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Neuralgia 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 2
    Neurological disorder NOS 2/60 (3.3%) 3 1/34 (2.9%) 2 0/35 (0%) 0 0/35 (0%) 0 2/60 (3.3%) 4 1/119 (0.8%) 1 1/33 (3%) 2
    Peripheral motor neuropathy 0/60 (0%) 0 0/34 (0%) 0 1/35 (2.9%) 5 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Peripheral sensory neuropathy 45/60 (75%) 664 23/34 (67.6%) 221 28/35 (80%) 233 31/35 (88.6%) 120 42/60 (70%) 349 94/119 (79%) 332 29/33 (87.9%) 259
    Syncope 5/60 (8.3%) 6 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 2/33 (6.1%) 2
    Syncope vasovagal 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Taste alteration 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Tremor 3/60 (5%) 3 2/34 (5.9%) 2 2/35 (5.7%) 2 1/35 (2.9%) 1 3/60 (5%) 3 1/119 (0.8%) 1 0/33 (0%) 0
    Psychiatric disorders
    Agitation 10/60 (16.7%) 12 2/34 (5.9%) 2 4/35 (11.4%) 7 0/35 (0%) 0 2/60 (3.3%) 6 0/119 (0%) 0 1/33 (3%) 1
    Anxiety 6/60 (10%) 9 1/34 (2.9%) 1 2/35 (5.7%) 2 1/35 (2.9%) 1 3/60 (5%) 4 4/119 (3.4%) 5 1/33 (3%) 3
    Confusion 7/60 (11.7%) 10 3/34 (8.8%) 7 1/35 (2.9%) 1 0/35 (0%) 0 1/60 (1.7%) 2 1/119 (0.8%) 1 3/33 (9.1%) 3
    Depression 6/60 (10%) 8 0/34 (0%) 0 1/35 (2.9%) 1 3/35 (8.6%) 7 2/60 (3.3%) 2 2/119 (1.7%) 2 1/33 (3%) 1
    Euphoria 3/60 (5%) 3 0/34 (0%) 0 1/35 (2.9%) 3 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Insomnia 11/60 (18.3%) 17 0/34 (0%) 0 4/35 (11.4%) 12 1/35 (2.9%) 1 9/60 (15%) 18 4/119 (3.4%) 6 3/33 (9.1%) 3
    Psychosis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 2 0/33 (0%) 0
    Renal and urinary disorders
    Bladder stenosis 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Renal failure 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Urinary frequency 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 5
    Urinary incontinence 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 4 0/119 (0%) 0 1/33 (3%) 1
    Urinary retention 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Reproductive system and breast disorders
    Erectile dysfunction 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 5 0/119 (0%) 0 0/33 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Apnea 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Cough 0/60 (0%) 0 2/34 (5.9%) 2 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Dyspnea 1/60 (1.7%) 1 2/34 (5.9%) 4 3/35 (8.6%) 3 1/35 (2.9%) 1 5/60 (8.3%) 11 4/119 (3.4%) 6 7/33 (21.2%) 14
    Hiccough 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 1/119 (0.8%) 1 0/33 (0%) 0
    Hypoxia 1/60 (1.7%) 2 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Pleural effusion 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 3/119 (2.5%) 3 0/33 (0%) 0
    Pleuritic pain 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 1/119 (0.8%) 1 0/33 (0%) 0
    Pneumonitis 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 2/119 (1.7%) 2 0/33 (0%) 0
    Respiratory tract hemorrhage 0/60 (0%) 0 1/34 (2.9%) 1 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Skin and subcutaneous tissue disorders
    Atrophy skin 1/60 (1.7%) 6 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Decubitus ulcer 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 1/33 (3%) 1
    Erythema multiforme 1/60 (1.7%) 1 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Petechiae 1/60 (1.7%) 6 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Rash desquamating 0/60 (0%) 0 0/34 (0%) 0 2/35 (5.7%) 2 0/35 (0%) 0 2/60 (3.3%) 2 0/119 (0%) 0 1/33 (3%) 1
    Skin disorder 1/60 (1.7%) 2 1/34 (2.9%) 1 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Sweating 5/60 (8.3%) 12 1/34 (2.9%) 4 0/35 (0%) 0 2/35 (5.7%) 2 1/60 (1.7%) 17 0/119 (0%) 0 0/33 (0%) 0
    Vascular disorders
    Hot flashes 0/60 (0%) 0 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 0/119 (0%) 0 0/33 (0%) 0
    Hypertension 3/60 (5%) 4 0/34 (0%) 0 1/35 (2.9%) 1 0/35 (0%) 0 0/60 (0%) 0 0/119 (0%) 0 0/33 (0%) 0
    Hypotension 2/60 (3.3%) 2 0/34 (0%) 0 0/35 (0%) 0 0/35 (0%) 0 1/60 (1.7%) 1 1/119 (0.8%) 1 0/33 (0%) 0
    Thrombosis 1/60 (1.7%) 1 0/34 (0%) 0 2/35 (5.7%) 4 1/35 (2.9%) 2 3/60 (5%) 3 3/119 (2.5%) 5 1/33 (3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Martha Lacy
    Organization Mayo Clinic
    Phone
    Email lacy.martha@mayo.edu
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT00558896
    Other Study ID Numbers:
    • CDR0000574742
    • P30CA015083
    • 07-003064
    • NCI-2009-01283
    • MC0789
    • NCT01219634
    First Posted:
    Nov 15, 2007
    Last Update Posted:
    Apr 18, 2018
    Last Verified:
    Mar 1, 2018