Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma

Sponsor
Washington University School of Medicine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02253316
Collaborator
Millennium Pharmaceuticals, Inc. (Industry), Multiple Myeloma Research Consortium (Other)
236
Enrollment
10
Locations
3
Arms
115.4
Anticipated Duration (Months)
23.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib.

In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.

09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.

09/30/2021: Following analysis 4 in 2021, analysis of the primary endpoint, all patients receiving lenalidomide maintenance will be transitioned off-study. Patients receiving ixazomib may remain on trial until disease progression or unacceptable toxicity at the discretion of the treating physician and the site principal investigator.

Study Design

Study Type:
Interventional
Actual Enrollment :
236 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of IRD (Ixazomib, Lenalidomide, & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
Actual Study Start Date :
Jan 20, 2015
Actual Primary Completion Date :
Feb 5, 2020
Anticipated Study Completion Date :
Aug 31, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone

Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.

Biological: Ixazomib
Other Names:
  • [14C]-ixazomib
  • [14C]-MLN9708
  • Drug: Lenalidomide
    Other Names:
  • Revlimid
  • Drug: Dexamethasone
    Other Names:
  • Aeroseb-Dex
  • Alba-Dex
  • Decaderm
  • Decadrol
  • Decadron
  • Decasone R.p.
  • Decaspray
  • Deenar
  • Deronil
  • Dex-4
  • Dexace
  • Dexameth
  • Dezone
  • Gammacorten
  • Hexadrol
  • Maxidex
  • Sk-Dexamethasone
  • Experimental: Maintenance Arm 1: Ixazomib

    Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.

    Biological: Ixazomib
    Other Names:
  • [14C]-ixazomib
  • [14C]-MLN9708
  • Experimental: Maintenance Arm 2: Lenalidomide

    Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.

    Drug: Lenalidomide
    Other Names:
  • Revlimid
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Improvement in Minimal Residual Disease (MRD) [After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)]

      For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.

    Secondary Outcome Measures

    1. MRD-negative Rate After ASCT [Prior to beginning consolidation treatment (Day -28 to Day 0)]

      For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing

    2. Toxicity of IRD Consolidation [After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)]

      For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.

    3. Response Rate of IRD Consolidation [After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)]

      For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.

    4. Progression-free Survival of IRD Consolidation [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

    5. Overall Survival of IRD Consolidation [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

    6. Compare Toxicity Between the Two Maintenance Arms [30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)]

      The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

    7. Compare Response Rate Between the Two Maintenance Arms [Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)]

      Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.

    8. Compare Progression-free Survival Between the Two Maintenance Arms [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

    9. Compare Overall Survival Between the Two Maintenance Arms [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

    10. Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms [Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)]

    11. Association of Progression-free Survival With MRD-negativity [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

    12. Association of Progression-free Survival With MRD-positivity [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

    13. Association of Overall Survival With MRD-negativity [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

    14. Association of Overall Survival With MRD-positivity [Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)]

      Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    Each patient must meet all of the following inclusion criteria to begin IRD Consolidation:
    • Between the ages of 18 and 70 years of age (inclusive) at time of enrollment

    • Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

    • Confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma with secondary amyloidosis are eligible.)

    • Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-16 months of the first dose of initial therapy

    • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2

    • Adequate organ function as defined below:

    Absolute neutrophil count (ANC) >= 1,000 mm3 Platelet count >= 75,000/mm3; platelet transfusions to help patient meet eligibility criteria are not allowed within 7 days before study enrollment Total bilirubin <= 1.5 x upper limit of normal range (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 x ULN Calculated creatinine clearance >= 30 mL/min

    • Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS program material. This is defined as either committing to continued abstinence from heterosexual intercourse or beginning TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last dose of lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing.

    • Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

    • All study participants must be registered into the mandatory Revlimind REMS program and be willing to comply with its requirements. Per standard Revlimid REMS program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS program.

    Exclusion Criteria

    Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

    • Female patients who are lactating or have a positive serum pregnancy test during the screening period

    • Evidence of MM disease progression any time prior to enrollment. Progression from smoldering/asymptomatic MM to symptomatic MM is not exclusionary.

    • Tandem autologous transplantation

    • History of plasma cell leukemia or MM CNS involvement

    • Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma until Day +28 post-transplant through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)

    • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

    • Prior organ transplant requiring immunosuppressive therapy

    • Active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive

    • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent

    • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib

    • Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma and secondary amyloidosis)

    • Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial infarction within the previous six months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease

    • Grade >= 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period

    • Major surgery within 14 days prior to enrollment

    • Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to enrollment

    • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days prior to enrollment and throughout the duration of this trial

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1City of HopeDuarteCaliforniaUnited States91010
    2University of California, San FranciscoSan FranciscoCaliforniaUnited States94143
    3Colorado Blood Cancer InstituteDenverColoradoUnited States80218
    4Emory University - Winship Cancer InstituteAtlantaGeorgiaUnited States30322
    5Karmanos Cancer InstituteDetroitMichiganUnited States48201
    6Mayo ClinicRochesterMinnesotaUnited States55905
    7Washington University School of MedicineSaint LouisMissouriUnited States62864
    8Icahn School of Medicine at Mount SinaiNew YorkNew YorkUnited States10029
    9Ohio State University Comprehensive Cancer CenterColumbusOhioUnited States43210
    10Tennessee Oncology, PLLCNashvilleTennesseeUnited States37203

    Sponsors and Collaborators

    • Washington University School of Medicine
    • Millennium Pharmaceuticals, Inc.
    • Multiple Myeloma Research Consortium

    Investigators

    • Principal Investigator: Ravi Vij, M.D., Washington University School of Medicine

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT02253316
    Other Study ID Numbers:
    • 201411060
    First Posted:
    Oct 1, 2014
    Last Update Posted:
    Nov 8, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Washington University School of Medicine
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. 09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
    Period Title: Consolidation
    STARTED23600
    COMPLETED21900
    NOT COMPLETED1700
    Period Title: Consolidation
    STARTED099116
    COMPLETED04635
    NOT COMPLETED05381

    Baseline Characteristics

    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & Dexamethasone
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.
    Overall Participants236
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    58
    Sex: Female, Male (Count of Participants)
    Female
    91
    38.6%
    Male
    145
    61.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    15
    6.4%
    Not Hispanic or Latino
    217
    91.9%
    Unknown or Not Reported
    4
    1.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.4%
    Asian
    8
    3.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    30
    12.7%
    White
    185
    78.4%
    More than one race
    1
    0.4%
    Unknown or Not Reported
    11
    4.7%
    Region of Enrollment (participants) [Number]
    United States
    236
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants With Improvement in Minimal Residual Disease (MRD)
    DescriptionFor the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.
    Time FrameAfter 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

    Outcome Measure Data

    Analysis Population Description
    Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 52 patients in consolidation were not evaluable for the outcome because 26 did not have appropriate VDJ rearrangements on clonoSEQ assessment, 10 did not have sample available from one or both time points, and 16 were removed prior to completion of 4 cycles of IRD.
    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. 09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
    Measure Participants18400
    Count of Participants [Participants]
    19
    8.1%
    2. Secondary Outcome
    TitleMRD-negative Rate After ASCT
    DescriptionFor the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing
    Time FramePrior to beginning consolidation treatment (Day -28 to Day 0)

    Outcome Measure Data

    Analysis Population Description
    Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 33 patients from consolidation were not evaluable for this outcome because 26 patients did not have appropriate VDJ rearrangements found on clonSEQ assessment and 7 patients did not have a sample available.
    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. 09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
    Measure Participants20300
    Count of Participants [Participants]
    51
    21.6%
    3. Secondary Outcome
    TitleToxicity of IRD Consolidation
    DescriptionFor the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.
    Time FrameAfter 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

    Outcome Measure Data

    Analysis Population Description
    Only participants in the consolidation portion of the trial are evaluable for this outcome measure. 10 patients in consolidation were not evaluable for this outcome because they discontinued prior to 4 cycles of IRD for reasons other than toxicity.
    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. 09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
    Measure Participants22600
    Count of Participants [Participants]
    7
    3%
    4. Secondary Outcome
    TitleResponse Rate of IRD Consolidation
    DescriptionFor the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.
    Time FrameAfter 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

    Outcome Measure Data

    Analysis Population Description
    Only participants in the consolidation portion of the trial are evaluable for this outcome measure.
    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. 09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
    Measure Participants23600
    Count of Participants [Participants]
    49
    20.8%
    5. Secondary Outcome
    TitleProgression-free Survival of IRD Consolidation
    DescriptionProgression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    TitleOverall Survival of IRD Consolidation
    DescriptionOverall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    TitleCompare Toxicity Between the Two Maintenance Arms
    DescriptionThe descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
    Time Frame30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    TitleCompare Response Rate Between the Two Maintenance Arms
    DescriptionResponse will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.
    Time FrameThrough completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    TitleCompare Progression-free Survival Between the Two Maintenance Arms
    DescriptionProgression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Secondary Outcome
    TitleCompare Overall Survival Between the Two Maintenance Arms
    DescriptionOverall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Secondary Outcome
    TitleRate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms
    Description
    Time FrameCycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Secondary Outcome
    TitleAssociation of Progression-free Survival With MRD-negativity
    DescriptionProgression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    13. Secondary Outcome
    TitleAssociation of Progression-free Survival With MRD-positivity
    DescriptionProgression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    14. Secondary Outcome
    TitleAssociation of Overall Survival With MRD-negativity
    DescriptionOverall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    15. Secondary Outcome
    TitleAssociation of Overall Survival With MRD-positivity
    DescriptionOverall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
    Time FrameUp to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame-Adverse events were collected from first dose of study treatment through 30 days after the completion of study treatment. -All-cause mortality time frame is from first dose of study treatment through 30 days after the completion of study treatment.
    Adverse Event Reporting Description
    Arm/Group TitleConsolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Arm/Group DescriptionConsolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
    All Cause Mortality
    Consolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Serious Adverse Events
    Consolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total45/236 (19.1%) 23/99 (23.2%) 35/116 (30.2%)
    Blood and lymphatic system disorders
    Pancytopenia0/236 (0%) 1/99 (1%) 0/116 (0%)
    Cardiac disorders
    Acute coronary syndrome0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Cardiac arrest0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Coronary artery calcification0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Coronary artery occlusion1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Myocardial infarction0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Pericardial effusion0/236 (0%) 1/99 (1%) 0/116 (0%)
    Gastrointestinal disorders
    Abdominal pain0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Diarrhea0/236 (0%) 2/99 (2%) 0/116 (0%)
    Gastric ulcer1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Gastritis1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Lower gastrointestinal hemorrhage1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Obstruction gastric1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Rectal hemorrhage1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Vomiting1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    General disorders
    Fever1/236 (0.4%) 2/99 (2%) 1/116 (0.9%)
    Rigors0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Hepatobiliary disorders
    Chloecystitis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Immune system disorders
    Anaphylaxis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Infections and infestations
    C. difficile infection1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Device related infection0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Eye infection0/236 (0%) 0/99 (0%) 0/116 (0%)
    Lung infection12/236 (5.1%) 2/99 (2%) 8/116 (6.9%)
    Salmonella1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Sepsis1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Skin infection0/236 (0%) 1/99 (1%) 0/116 (0%)
    Upper respiratory infection12/236 (5.1%) 7/99 (7.1%) 9/116 (7.8%)
    Injury, poisoning and procedural complications
    Fall1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Ixazomib overdose1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Metabolism and nutrition disorders
    Dehydration0/236 (0%) 1/99 (1%) 0/116 (0%)
    Diabetic ketoacidosis1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Musculoskeletal and connective tissue disorders
    Chest wall pain0/236 (0%) 1/99 (1%) 0/116 (0%)
    Spinal cord compression (myeloma progression)0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphoblastic leukemia0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Basal cell carcinoma1/236 (0.4%) 0/99 (0%) 4/116 (3.4%)
    Breast cancer0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Breast cancer in Situ (DCIS)0/236 (0%) 1/99 (1%) 0/116 (0%)
    Compression fracture (myeloma progression)0/236 (0%) 1/99 (1%) 0/116 (0%)
    Melanoma0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Myelodysplastic syndrome0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Pancreatic cancer1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Papillary urothelial carcinoma1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Plasmacytoma (myeloma progression)1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Prostate cancer0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Squamous cell carcinoma0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Nervous system disorders
    Headache0/236 (0%) 1/99 (1%) 0/116 (0%)
    Neuropathic back pain1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Syncope0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Pregnancy, puerperium and perinatal conditions
    Unintended pregnancy1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Psychiatric disorders
    Agitation0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Confusion1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Panic attack0/236 (0%) 0/99 (0%) 0/116 (0%)
    Renal and urinary disorders
    Acute kidney injury1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Skin and subcutaneous tissue disorders
    Erythroderma0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Vascular disorders
    Lymphedema1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Thromboembolic event1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Other (Not Including Serious) Adverse Events
    Consolidation: Ixazomib, Lenalidomide, & DexamethasoneMaintenance Arm 1: IxazomibMaintenance Arm 2: Lenalidomide
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total236/236 (100%) 99/99 (100%) 116/116 (100%)
    Blood and lymphatic system disorders
    Anemia120/236 (50.8%) 43/99 (43.4%) 44/116 (37.9%)
    Febrile neutropenia1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Hemolysis0/236 (0%) 1/99 (1%) 0/116 (0%)
    Leukocytosis1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Thrombotic thrombocytopenic purpura1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Cardiac disorders
    Atrial fibrillation1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Atrial flutter1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Chest pain - cardiac2/236 (0.8%) 0/99 (0%) 2/116 (1.7%)
    Palpitations3/236 (1.3%) 1/99 (1%) 3/116 (2.6%)
    Sinus bradycardia2/236 (0.8%) 0/99 (0%) 1/116 (0.9%)
    Sinus tachycardia3/236 (1.3%) 0/99 (0%) 2/116 (1.7%)
    Ear and labyrinth disorders
    Ear pain1/236 (0.4%) 0/99 (0%) 2/116 (1.7%)
    Eustachian tube disfunction1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Hearing impaired1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Tinnitus3/236 (1.3%) 1/99 (1%) 4/116 (3.4%)
    Vertigo1/236 (0.4%) 2/99 (2%) 2/116 (1.7%)
    Endocrine disorders
    Cushingoid1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Hyperthyroidism1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Hypoparathyroidism1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Hypothyroidism0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Thyroiditis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Eye disorders
    Allergic eye irritation0/236 (0%) 1/99 (1%) 0/116 (0%)
    Blepharitis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Blurred vision10/236 (4.2%) 8/99 (8.1%) 7/116 (6%)
    Bulging retinas1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Cataract1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Chalazion1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Conjuctivitis3/236 (1.3%) 1/99 (1%) 1/116 (0.9%)
    Dry eye3/236 (1.3%) 3/99 (3%) 0/116 (0%)
    Eye pain2/236 (0.8%) 0/99 (0%) 1/116 (0.9%)
    Eye redness0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Floaters0/236 (0%) 2/99 (2%) 0/116 (0%)
    Glaucoma0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Hordeolum1/236 (0.4%) 2/99 (2%) 0/116 (0%)
    Ptosis0/236 (0%) 1/99 (1%) 0/116 (0%)
    Vitreous hemorrhage0/236 (0%) 1/99 (1%) 0/116 (0%)
    Watering eyes0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Gastrointestinal disorders
    Abdominal distension0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Abdominal pain14/236 (5.9%) 11/99 (11.1%) 7/116 (6%)
    Anal hemorrhage1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Bloating4/236 (1.7%) 2/99 (2%) 5/116 (4.3%)
    Colitis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Constipation70/236 (29.7%) 22/99 (22.2%) 27/116 (23.3%)
    Dental caries0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Diarrhea75/236 (31.8%) 46/99 (46.5%) 59/116 (50.9%)
    Dry mouth13/236 (5.5%) 3/99 (3%) 6/116 (5.2%)
    Dyspepsia3/236 (1.3%) 1/99 (1%) 5/116 (4.3%)
    Dysphagia3/236 (1.3%) 1/99 (1%) 2/116 (1.7%)
    Esophageal spasms1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Flatulence4/236 (1.7%) 2/99 (2%) 1/116 (0.9%)
    Gastric ulcer0/236 (0%) 1/99 (1%) 0/116 (0%)
    Gastroesophageal reflux disease13/236 (5.5%) 2/99 (2%) 8/116 (6.9%)
    Gastrointestinal pain1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Hematochezia1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Hemorrhoids3/236 (1.3%) 3/99 (3%) 2/116 (1.7%)
    Ileus0/236 (0%) 1/99 (1%) 0/116 (0%)
    Irritable bowel syndrome0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Mucositis oral4/236 (1.7%) 0/99 (0%) 1/116 (0.9%)
    Nausea67/236 (28.4%) 46/99 (46.5%) 27/116 (23.3%)
    Oral dysesthesia1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Oral pain4/236 (1.7%) 0/99 (0%) 4/116 (3.4%)
    Stomach pain1/236 (0.4%) 2/99 (2%) 1/116 (0.9%)
    Sugar cravings1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Tongue laceration0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Tooth changes NOS0/236 (0%) 1/99 (1%) 0/116 (0%)
    Toothache2/236 (0.8%) 0/99 (0%) 2/116 (1.7%)
    Tubulovillous adenoma1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Typhlitis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Vomiting33/236 (14%) 21/99 (21.2%) 13/116 (11.2%)
    General disorders
    Chills6/236 (2.5%) 8/99 (8.1%) 4/116 (3.4%)
    Diaphoresis3/236 (1.3%) 2/99 (2%) 6/116 (5.2%)
    Edema face6/236 (2.5%) 3/99 (3%) 1/116 (0.9%)
    Edema limbs39/236 (16.5%) 10/99 (10.1%) 18/116 (15.5%)
    Edema trunk0/236 (0%) 1/99 (1%) 0/116 (0%)
    Facial pain0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Fatigue108/236 (45.8%) 49/99 (49.5%) 47/116 (40.5%)
    Fever17/236 (7.2%) 11/99 (11.1%) 18/116 (15.5%)
    Flu like symptoms8/236 (3.4%) 12/99 (12.1%) 7/116 (6%)
    Gait disturbance2/236 (0.8%) 1/99 (1%) 0/116 (0%)
    Infusion related reaction0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Injection site reaction1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Irritability2/236 (0.8%) 0/99 (0%) 1/116 (0.9%)
    Liver abscess0/236 (0%) 1/99 (1%) 0/116 (0%)
    Localized edema2/236 (0.8%) 8/99 (8.1%) 4/116 (3.4%)
    Malaise0/236 (0%) 0/99 (0%) 3/116 (2.6%)
    Non-cardiac chest pain5/236 (2.1%) 1/99 (1%) 6/116 (5.2%)
    Pain32/236 (13.6%) 35/99 (35.4%) 37/116 (31.9%)
    Hepatobiliary disorders
    Cholecystitis0/236 (0%) 2/99 (2%) 0/116 (0%)
    Gallbladder fistula1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Gallbladder obstruction1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Gallbladder pain0/236 (0%) 1/99 (1%) 0/116 (0%)
    Gallstones0/236 (0%) 1/99 (1%) 0/116 (0%)
    Immune system disorders
    Allergic reaction0/236 (0%) 3/99 (3%) 0/116 (0%)
    Lymphadenopathy0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Tongue swelling0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Infections and infestations
    Bladder infection0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Bronchial infection0/236 (0%) 3/99 (3%) 6/116 (5.2%)
    C. difficile infection1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Ear infection0/236 (0%) 1/99 (1%) 0/116 (0%)
    Eye infection0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Gum infection0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Laryngitis0/236 (0%) 1/99 (1%) 0/116 (0%)
    Lung infection5/236 (2.1%) 6/99 (6.1%) 5/116 (4.3%)
    Mucosal infection3/236 (1.3%) 1/99 (1%) 2/116 (1.7%)
    Nail infection1/236 (0.4%) 1/99 (1%) 3/116 (2.6%)
    Otitis media4/236 (1.7%) 2/99 (2%) 2/116 (1.7%)
    Papulopustular rash0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Parasitic infection0/236 (0%) 1/99 (1%) 0/116 (0%)
    Paronychia2/236 (0.8%) 0/99 (0%) 0/116 (0%)
    Peripheral nerve infection1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Pharyngitis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Pleural infection0/236 (0%) 1/99 (1%) 0/116 (0%)
    Rash pustular2/236 (0.8%) 2/99 (2%) 0/116 (0%)
    Shingles1/236 (0.4%) 3/99 (3%) 0/116 (0%)
    Sinusitis4/236 (1.7%) 4/99 (4%) 5/116 (4.3%)
    Skin infection5/236 (2.1%) 3/99 (3%) 7/116 (6%)
    Small intestine infection1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Soft tissue infection1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Testicular infection0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Tooth infection1/236 (0.4%) 1/99 (1%) 3/116 (2.6%)
    Upper respiratory infection69/236 (29.2%) 33/99 (33.3%) 52/116 (44.8%)
    Urinary tract infection7/236 (3%) 5/99 (5.1%) 4/116 (3.4%)
    Vaginal infection1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Wound infection0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Yeast infection0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Injury, poisoning and procedural complications
    Bruising7/236 (3%) 6/99 (6.1%) 7/116 (6%)
    Burn0/236 (0%) 1/99 (1%) 0/116 (0%)
    Burn from chemical peel0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Burn from sun exposure0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Crown dislodged1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Fall6/236 (2.5%) 7/99 (7.1%) 7/116 (6%)
    Fracture3/236 (1.3%) 1/99 (1%) 0/116 (0%)
    Tick bite0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Investigations
    Activated partial thromboplastin time prolonged0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Alanine aminotransferase increased39/236 (16.5%) 14/99 (14.1%) 23/116 (19.8%)
    Alkaline phosphatase increased18/236 (7.6%) 8/99 (8.1%) 12/116 (10.3%)
    Aspartate aminotransferase increased29/236 (12.3%) 13/99 (13.1%) 22/116 (19%)
    Blood bilirubin increased7/236 (3%) 4/99 (4%) 5/116 (4.3%)
    Cholesterol high0/236 (0%) 2/99 (2%) 1/116 (0.9%)
    Creatinine increased35/236 (14.8%) 16/99 (16.2%) 21/116 (18.1%)
    Fibrinogen decreased0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    GGT increased2/236 (0.8%) 0/99 (0%) 0/116 (0%)
    INR increased0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Lipase increased1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Lymphocyte count decreased144/236 (61%) 48/99 (48.5%) 52/116 (44.8%)
    Lymphocyte count increased1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Neutrophil count decreased64/236 (27.1%) 22/99 (22.2%) 68/116 (58.6%)
    Platelet count decreased97/236 (41.1%) 30/99 (30.3%) 47/116 (40.5%)
    Prostate specific antigen increased0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Serum amylase increased1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Transminitis NOS1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Weight gain8/236 (3.4%) 1/99 (1%) 2/116 (1.7%)
    Weight loss1/236 (0.4%) 4/99 (4%) 3/116 (2.6%)
    White blood cell decreased104/236 (44.1%) 29/99 (29.3%) 55/116 (47.4%)
    Metabolism and nutrition disorders
    Anorexia5/236 (2.1%) 4/99 (4%) 9/116 (7.8%)
    Dehydration3/236 (1.3%) 1/99 (1%) 1/116 (0.9%)
    Hypercalcemia6/236 (2.5%) 5/99 (5.1%) 5/116 (4.3%)
    Hyperglycemia80/236 (33.9%) 22/99 (22.2%) 25/116 (21.6%)
    Hyperkalemia8/236 (3.4%) 7/99 (7.1%) 7/116 (6%)
    Hypermagnesemia2/236 (0.8%) 0/99 (0%) 1/116 (0.9%)
    Hypernatremia15/236 (6.4%) 7/99 (7.1%) 6/116 (5.2%)
    Hypertriglyceridemia0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Hyperuricemia4/236 (1.7%) 4/99 (4%) 2/116 (1.7%)
    Hypoalbuminemia23/236 (9.7%) 2/99 (2%) 3/116 (2.6%)
    Hypocalcemia30/236 (12.7%) 4/99 (4%) 14/116 (12.1%)
    Hypoglycemia15/236 (6.4%) 7/99 (7.1%) 13/116 (11.2%)
    Hypokalemia30/236 (12.7%) 10/99 (10.1%) 24/116 (20.7%)
    Hypomagnesemia3/236 (1.3%) 1/99 (1%) 0/116 (0%)
    Hyponatremia14/236 (5.9%) 2/99 (2%) 6/116 (5.2%)
    Hypophosphatemia6/236 (2.5%) 2/99 (2%) 2/116 (1.7%)
    Vitamin B12 deficiency0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Vitamin D definciency0/236 (0%) 0/99 (0%) 3/116 (2.6%)
    Musculoskeletal and connective tissue disorders
    Achilles tendinosis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Arthralgia8/236 (3.4%) 6/99 (6.1%) 23/116 (19.8%)
    Arthritis3/236 (1.3%) 11/99 (11.1%) 7/116 (6%)
    Avascular necrosis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Back pain59/236 (25%) 31/99 (31.3%) 50/116 (43.1%)
    Bone pain9/236 (3.8%) 11/99 (11.1%) 10/116 (8.6%)
    Bone spur0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Chest wall pain7/236 (3%) 1/99 (1%) 1/116 (0.9%)
    Fibromyalgia0/236 (0%) 1/99 (1%) 0/116 (0%)
    Flank pain9/236 (3.8%) 5/99 (5.1%) 5/116 (4.3%)
    Generalized muscle weakness4/236 (1.7%) 4/99 (4%) 3/116 (2.6%)
    Gout0/236 (0%) 1/99 (1%) 0/116 (0%)
    Hernia3/236 (1.3%) 0/99 (0%) 2/116 (1.7%)
    Jaw pain1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Joint range of motion decreased0/236 (0%) 1/99 (1%) 0/116 (0%)
    Meniscus tear1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Muscle cramping12/236 (5.1%) 8/99 (8.1%) 19/116 (16.4%)
    Muscle weakness left-sided1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Muscle weakness lower limb3/236 (1.3%) 1/99 (1%) 0/116 (0%)
    Muscle weakness trunk0/236 (0%) 2/99 (2%) 0/116 (0%)
    Muscle weakness upper limb0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Myalgia18/236 (7.6%) 11/99 (11.1%) 25/116 (21.6%)
    Neck pain5/236 (2.1%) 6/99 (6.1%) 9/116 (7.8%)
    Osteonecrosis of jaw0/236 (0%) 2/99 (2%) 0/116 (0%)
    Osteoporosis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Pain in extremity32/236 (13.6%) 25/99 (25.3%) 28/116 (24.1%)
    Patellar dislocation0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Plantar fasciitis0/236 (0%) 1/99 (1%) 0/116 (0%)
    Rhabdomyolysis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Spinal stenosis0/236 (0%) 1/99 (1%) 0/116 (0%)
    Temporomandibular joint syndrome0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign nevi0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Benign polyp0/236 (0%) 1/99 (1%) 0/116 (0%)
    Boil0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Cyst2/236 (0.8%) 1/99 (1%) 6/116 (5.2%)
    Lump NOS1/236 (0.4%) 1/99 (1%) 3/116 (2.6%)
    Melanoma0/236 (0%) 1/99 (1%) 0/116 (0%)
    Plasmacytoma (myeloma progression)0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Pulmonary nodule1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Seborrheic keratosis0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Thyroid nodule0/236 (0%) 1/99 (1%) 0/116 (0%)
    Nervous system disorders
    Akathisia0/236 (0%) 1/99 (1%) 0/116 (0%)
    Amnesia0/236 (0%) 2/99 (2%) 1/116 (0.9%)
    Concentration impairment0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Dizziness19/236 (8.1%) 9/99 (9.1%) 13/116 (11.2%)
    Dysarthria1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Dysgeusia17/236 (7.2%) 2/99 (2%) 6/116 (5.2%)
    Dystonic reaction1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Facial nerve disorder0/236 (0%) 1/99 (1%) 0/116 (0%)
    Headache23/236 (9.7%) 7/99 (7.1%) 19/116 (16.4%)
    Hypersomnia0/236 (0%) 1/99 (1%) 0/116 (0%)
    Memory impairment1/236 (0.4%) 3/99 (3%) 1/116 (0.9%)
    Movements involuntary1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Neuralgia0/236 (0%) 1/99 (1%) 0/116 (0%)
    Paresthesia10/236 (4.2%) 7/99 (7.1%) 10/116 (8.6%)
    Parkinsonism0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Peripheral motor neuropathy13/236 (5.5%) 7/99 (7.1%) 12/116 (10.3%)
    Peripheral sensory neuropathy88/236 (37.3%) 49/99 (49.5%) 51/116 (44%)
    Phantom pain1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Presyncope2/236 (0.8%) 0/99 (0%) 0/116 (0%)
    Seizure0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Syncope3/236 (1.3%) 2/99 (2%) 0/116 (0%)
    Tremor6/236 (2.5%) 1/99 (1%) 3/116 (2.6%)
    Psychiatric disorders
    Agitation10/236 (4.2%) 0/99 (0%) 2/116 (1.7%)
    Anxiety11/236 (4.7%) 2/99 (2%) 11/116 (9.5%)
    Confusion3/236 (1.3%) 1/99 (1%) 1/116 (0.9%)
    Delirium0/236 (0%) 1/99 (1%) 0/116 (0%)
    Depression11/236 (4.7%) 7/99 (7.1%) 8/116 (6.9%)
    Hallucinations0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Insomnia58/236 (24.6%) 11/99 (11.1%) 14/116 (12.1%)
    Panic attack0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Psychosocial difficulties0/236 (0%) 1/99 (1%) 0/116 (0%)
    Recurrent dreams0/236 (0%) 1/99 (1%) 0/116 (0%)
    Restlessness1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Stress0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Renal and urinary disorders
    Acute kidney injury0/236 (0%) 1/99 (1%) 2/116 (1.7%)
    Bladder stones1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Chronic kidney disease0/236 (0%) 2/99 (2%) 2/116 (1.7%)
    Cystitis noninfective0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Dysuria0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Hematuria1/236 (0.4%) 2/99 (2%) 1/116 (0.9%)
    Kidney stones2/236 (0.8%) 0/99 (0%) 0/116 (0%)
    Proteinuria0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Renal calculi3/236 (1.3%) 1/99 (1%) 0/116 (0%)
    Urinary frequency5/236 (2.1%) 4/99 (4%) 1/116 (0.9%)
    Urinary incontinence0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Urinary retention2/236 (0.8%) 2/99 (2%) 0/116 (0%)
    Urinary tract pain1/236 (0.4%) 2/99 (2%) 4/116 (3.4%)
    Urinary urgency1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Urostomy obstruction1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Reproductive system and breast disorders
    Cystocele0/236 (0%) 1/99 (1%) 0/116 (0%)
    Erectile dysfunction1/236 (0.4%) 0/99 (0%) 2/116 (1.7%)
    Nipple pain0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Penile pain1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Premenstrual syndrome0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Prostatic obstruction0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Vaginal dryness0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Vaginal hemorrhage2/236 (0.8%) 0/99 (0%) 0/116 (0%)
    Vaginal pain0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis8/236 (3.4%) 9/99 (9.1%) 4/116 (3.4%)
    Aspiration0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Asthma0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    COPD exacerbation1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Cough36/236 (15.3%) 29/99 (29.3%) 35/116 (30.2%)
    Dyspnea32/236 (13.6%) 21/99 (21.2%) 20/116 (17.2%)
    Epistaxis5/236 (2.1%) 0/99 (0%) 2/116 (1.7%)
    Hemoptysis1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Hiccups8/236 (3.4%) 1/99 (1%) 2/116 (1.7%)
    Hoarseness3/236 (1.3%) 2/99 (2%) 2/116 (1.7%)
    Hypoxia0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Laryngeal inflammation0/236 (0%) 1/99 (1%) 2/116 (1.7%)
    Nasal congestion15/236 (6.4%) 9/99 (9.1%) 18/116 (15.5%)
    Nasal nares inflammation1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Pleuritic pain0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Pneumonitis1/236 (0.4%) 2/99 (2%) 1/116 (0.9%)
    Postnasal drip3/236 (1.3%) 5/99 (5.1%) 8/116 (6.9%)
    Productive cough11/236 (4.7%) 4/99 (4%) 7/116 (6%)
    Pulmonary edema1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Sinus disorder1/236 (0.4%) 1/99 (1%) 2/116 (1.7%)
    Sleep apnea0/236 (0%) 1/99 (1%) 0/116 (0%)
    Sneezing0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Sore throat11/236 (4.7%) 5/99 (5.1%) 5/116 (4.3%)
    Wheezing4/236 (1.7%) 0/99 (0%) 2/116 (1.7%)
    Skin and subcutaneous tissue disorders
    Actinic keratosis0/236 (0%) 0/99 (0%) 2/116 (1.7%)
    Allergic contact dermatitis0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Alopecia1/236 (0.4%) 2/99 (2%) 0/116 (0%)
    Brittle nails0/236 (0%) 1/99 (1%) 0/116 (0%)
    Bullous dermatitis0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Dry skin18/236 (7.6%) 6/99 (6.1%) 12/116 (10.3%)
    Eczema0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Erythema multiforme1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Hyperhidrosis2/236 (0.8%) 0/99 (0%) 4/116 (3.4%)
    Hypohidrosis1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Ingrown toenail1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Nail discoloration0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Nail ridging0/236 (0%) 1/99 (1%) 0/116 (0%)
    Pain of skin1/236 (0.4%) 1/99 (1%) 1/116 (0.9%)
    Palmar-plantar erythrodysesthesia syndrome0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Peeling skin0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Petechiae1/236 (0.4%) 1/99 (1%) 0/116 (0%)
    Photosensitivity1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Poison ivy2/236 (0.8%) 0/99 (0%) 0/116 (0%)
    Pruritus8/236 (3.4%) 7/99 (7.1%) 5/116 (4.3%)
    Rash acneiform0/236 (0%) 2/99 (2%) 1/116 (0.9%)
    Rash maculo-papular34/236 (14.4%) 22/99 (22.2%) 25/116 (21.6%)
    Roseola0/236 (0%) 1/99 (1%) 0/116 (0%)
    Skin cancer NOS0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Skin hyperpigmentation2/236 (0.8%) 0/99 (0%) 2/116 (1.7%)
    Skin hypersensitiviy1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Skin laceration2/236 (0.8%) 4/99 (4%) 1/116 (0.9%)
    Skin ulceration0/236 (0%) 2/99 (2%) 2/116 (1.7%)
    Urticaria0/236 (0%) 1/99 (1%) 0/116 (0%)
    Surgical and medical procedures
    Arthroscopy of knee0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Foot surgery0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Hernia repair0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Oral surgery0/236 (0%) 1/99 (1%) 0/116 (0%)
    Root canal0/236 (0%) 1/99 (1%) 1/116 (0.9%)
    Spine surgery1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Tooth extraction0/236 (0%) 1/99 (1%) 0/116 (0%)
    Vascular disorders
    Flushing6/236 (2.5%) 1/99 (1%) 0/116 (0%)
    Hematoma0/236 (0%) 0/99 (0%) 1/116 (0.9%)
    Hot flashes7/236 (3%) 6/99 (6.1%) 10/116 (8.6%)
    Hypertension33/236 (14%) 20/99 (20.2%) 21/116 (18.1%)
    Hyperviscosity0/236 (0%) 1/99 (1%) 0/116 (0%)
    Hypotension10/236 (4.2%) 2/99 (2%) 4/116 (3.4%)
    Lymphedema1/236 (0.4%) 0/99 (0%) 1/116 (0.9%)
    Superficial thrombophlebitis1/236 (0.4%) 0/99 (0%) 0/116 (0%)
    Thromboembolic event5/236 (2.1%) 3/99 (3%) 5/116 (4.3%)
    Vascular calcification0/236 (0%) 0/99 (0%) 1/116 (0.9%)

    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/TitleRavi Vij, M.D.
    OrganizationWashington University School of Medicine
    Phone314-454-8323
    Emailrvij@wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT02253316
    Other Study ID Numbers:
    • 201411060
    First Posted:
    Oct 1, 2014
    Last Update Posted:
    Nov 8, 2021
    Last Verified:
    Nov 1, 2021