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
10
3
115.4
23.6
0.2
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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
| Arm | Intervention/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:
Drug: Lenalidomide
Other Names:
Drug: Dexamethasone
Other Names:
|
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Response includes stringent complete response (sCR) and complete response (CR). sCR requires all of the following: CR as defined below Normal free light chain ratio (0.26-1.65) Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence CR requires all of the following: Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65) <5% plasma cells in the bone marrow Disappearance of soft tissue plasmacytoma
- 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.
- 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.
- 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)]
- 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.
- 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.
- 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.
- 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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | University of California, San Francisco | San Francisco | California | United States | 94143 |
| 3 | Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
| 4 | Emory University - Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 5 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 6 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 7 | Washington University School of Medicine | Saint Louis | Missouri | United States | 62864 |
| 8 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 9 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
| 10 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37203 |
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:
Jul 12, 2022
Last Verified:
Jul 1, 2022
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 Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 | |||
| STARTED | 236 | 0 | 0 |
| COMPLETED | 220 | 0 | 0 |
| NOT COMPLETED | 16 | 0 | 0 |
| Period Title: Consolidation | |||
| STARTED | 0 | 99 | 116 |
| COMPLETED | 0 | 54 | 50 |
| NOT COMPLETED | 0 | 45 | 66 |
Baseline Characteristics
| Arm/Group Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 236 |
| 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
| Title | Number of Participants With Improvement in Minimal Residual Disease (MRD) |
|---|---|
| Description | 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. |
| Time Frame | After 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 Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 Participants | 184 | 0 | 0 |
| Count of Participants [Participants] |
19
8.1%
|
| Title | MRD-negative Rate After ASCT |
|---|---|
| Description | 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 |
| Time Frame | Prior 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 Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 Participants | 203 | 0 | 0 |
| Count of Participants [Participants] |
51
21.6%
|
| Title | Toxicity of IRD Consolidation |
|---|---|
| Description | For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity. |
| Time Frame | After 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 Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 Participants | 226 | 0 | 0 |
| Count of Participants [Participants] |
7
3%
|
| Title | Response Rate of IRD Consolidation |
|---|---|
| Description | 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. |
| Time Frame | After 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 Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 Participants | 236 | 0 | 0 |
| Count of Participants [Participants] |
49
20.8%
|
| Title | Progression-free Survival of IRD Consolidation |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Overall Survival of IRD Consolidation |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Compare Toxicity Between the Two Maintenance Arms |
|---|---|
| Description | 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. |
| Time Frame | 30 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 |
| Title | Compare Response Rate Between the Two Maintenance Arms |
|---|---|
| Description | Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR). sCR requires all of the following: CR as defined below Normal free light chain ratio (0.26-1.65) Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence CR requires all of the following: Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65) <5% plasma cells in the bone marrow Disappearance of soft tissue plasmacytoma |
| Time Frame | Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome measure is only for participants who went onto the maintenance arms. Participants in the maintenance arms were not evaluable for this outcome measure if they were removed from treatment for reasons other than progressive disease prior to Month 13. |
| Arm/Group Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 Participants | 0 | 91 | 109 |
| Count of Participants [Participants] |
50
21.2%
|
80
NaN
|
| Title | Compare Progression-free Survival Between the Two Maintenance Arms |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Compare Overall Survival Between the Two Maintenance Arms |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms |
|---|---|
| Description | |
| Time Frame | Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome measure is only for participants who went onto the maintenance arms. For the maintenance arms, the overall number of participants analyzed only includes those participants who were MRD positive at the start of maintenance. |
| Arm/Group Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide |
|---|---|---|---|
| Arm/Group Description | 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. | 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 Participants | 0 | 57 | 52 |
| Count of Participants [Participants] |
5
2.1%
|
11
NaN
|
| Title | Association of Progression-free Survival With MRD-negativity |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Association of Progression-free Survival With MRD-positivity |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Association of Overall Survival With MRD-negativity |
|---|---|
| Description | 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. |
| Time Frame | Up 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 |
| Title | Association of Overall Survival With MRD-positivity |
|---|---|
| Description | 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. |
| Time Frame | Up 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 Title | Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide | |||
| Arm/Group Description | 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. | 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, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
Serious Adverse Events |
||||||
| Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 45/236 (19.1%) | 23/99 (23.2%) | 48/116 (41.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Pancytopenia (myeloma progression) | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Cardiac disorders | ||||||
| Acute coronary syndrome | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Cardiac arrest | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Coronary artery calcification | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Coronary artery occlusion | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Myocardial infarction | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Pericardial effusion | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Diarrhea | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Gastric ulcer | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Gastritis | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Ileus | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Lower gastrointestinal hemorrhage | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Obstruction gastric | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Vomiting | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| General disorders | ||||||
| Fever | 1/236 (0.4%) | 2/99 (2%) | 2/116 (1.7%) | |||
| Pleuritic pain | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Rigors | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hepatobiliary disorders | ||||||
| Chloecystitis | 0/236 (0%) | 0/99 (0%) | 4/116 (3.4%) | |||
| Immune system disorders | ||||||
| Anaphylaxis - shellfish | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Infections and infestations | ||||||
| C. difficile infection | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Device related infection | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Eye infection | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Lung infection | 13/236 (5.5%) | 2/99 (2%) | 11/116 (9.5%) | |||
| Salmonella enteritis infection | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Sepsis | 1/236 (0.4%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Skin infection | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Upper respiratory infection | 8/236 (3.4%) | 12/99 (12.1%) | 10/116 (8.6%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 1/236 (0.4%) | 1/99 (1%) | 0/116 (0%) | |||
| Ixazomib overdose | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Diabetic ketoacidosis | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Chest wall pain | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Compression fracture (myeloma progression) | 0/236 (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 leukemia | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Basal cell carcinoma | 1/236 (0.4%) | 0/99 (0%) | 5/116 (4.3%) | |||
| Breast cancer | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Breast cancer in Situ (DCIS) | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Melanoma | 0/236 (0%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Myelodysplastic syndrome | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Pancreatic cancer | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Papillary urothelial carcinoma | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Plasmacytoma (myeloma progression) | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Prostate cancer | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Squamous cell carcinoma | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Tubulovillous adenoma | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Nervous system disorders | ||||||
| Akathisia | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Neuropathic back pain | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Occular migraine (stroke concern) | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Syncope | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Unintended pregnancy | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Psychiatric disorders | ||||||
| Agitation | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Altered mental status | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Confusion | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Panic attack | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Renal calculi | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Erythroderma | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Vascular disorders | ||||||
| Lymphedema | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Thromboembolic event | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | Maintenance Arm 1: Ixazomib | Maintenance Arm 2: Lenalidomide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 236/236 (100%) | 99/99 (100%) | 116/116 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anemia | 120/236 (50.8%) | 43/99 (43.4%) | 57/116 (49.1%) | |||
| Febrile neutropenia | 1/236 (0.4%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Hemolysis | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Leukocytosis | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Thrombotic thrombocytopenic purpura | 1/236 (0.4%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Atrial flutter | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Chest pain - cardiac | 3/236 (1.3%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Palpitations | 3/236 (1.3%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Sinus bradycardia | 2/236 (0.8%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Sinus tachycardia | 3/236 (1.3%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Ear and labyrinth disorders | ||||||
| Ear pain | 1/236 (0.4%) | 0/99 (0%) | 4/116 (3.4%) | |||
| Eustachian tube disfunction | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hearing impaired | 1/236 (0.4%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Middle ear inflammation | 3/236 (1.3%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Tinnitus | 3/236 (1.3%) | 2/99 (2%) | 4/116 (3.4%) | |||
| Vertigo | 1/236 (0.4%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Endocrine disorders | ||||||
| Cushingoid | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Hyperthyroidism | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Hypoparathyroidism | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Hypothyroidism | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Thyroiditis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Eye disorders | ||||||
| Allergic eye irritation | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Blepharitis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Blurred vision | 10/236 (4.2%) | 8/99 (8.1%) | 8/116 (6.9%) | |||
| Bulging retinas | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Cataract | 1/236 (0.4%) | 1/99 (1%) | 0/116 (0%) | |||
| Chalazion | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Conjuctivitis | 3/236 (1.3%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Dry eye | 3/236 (1.3%) | 3/99 (3%) | 1/116 (0.9%) | |||
| Eye pain | 2/236 (0.8%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Floaters | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Glaucoma | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Itchy eyes | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Ptosis | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Vitreous hemorrhage | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Watering eyes | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal distension | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Abdominal pain | 14/236 (5.9%) | 7/99 (7.1%) | 13/116 (11.2%) | |||
| Anal hemorrhage | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Bloating | 4/236 (1.7%) | 1/99 (1%) | 6/116 (5.2%) | |||
| Bloody stool | 1/236 (0.4%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Colitis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Constipation | 70/236 (29.7%) | 18/99 (18.2%) | 34/116 (29.3%) | |||
| Dental caries | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Diarrhea | 75/236 (31.8%) | 43/99 (43.4%) | 74/116 (63.8%) | |||
| Dry mouth | 13/236 (5.5%) | 4/99 (4%) | 6/116 (5.2%) | |||
| Dyspepsia | 3/236 (1.3%) | 1/99 (1%) | 5/116 (4.3%) | |||
| Dysphagia | 3/236 (1.3%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Esophageal spasms | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Esophagitis | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Flatulence | 5/236 (2.1%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Gastric ulcer | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Gastroesophageal reflux disease | 13/236 (5.5%) | 2/99 (2%) | 8/116 (6.9%) | |||
| Gastrointestinal pain | 1/236 (0.4%) | 1/99 (1%) | 0/116 (0%) | |||
| Hemorrhoids | 3/236 (1.3%) | 4/99 (4%) | 1/116 (0.9%) | |||
| Hernia | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Irritable bowel syndrome | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Mucositis oral | 4/236 (1.7%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Nausea | 67/236 (28.4%) | 50/99 (50.5%) | 29/116 (25%) | |||
| Oral dysesthesia | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Oral pain | 4/236 (1.7%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Stomach pain | 1/236 (0.4%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Sugar cravings | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Tooth changes NOS | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Toothache | 2/236 (0.8%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Typhlitis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Vomiting | 33/236 (14%) | 20/99 (20.2%) | 16/116 (13.8%) | |||
| General disorders | ||||||
| Chills | 6/236 (2.5%) | 7/99 (7.1%) | 7/116 (6%) | |||
| Edema face | 6/236 (2.5%) | 3/99 (3%) | 2/116 (1.7%) | |||
| Edema limbs | 40/236 (16.9%) | 13/99 (13.1%) | 19/116 (16.4%) | |||
| Edema trunk | 0/236 (0%) | 0/99 (0%) | 0/116 (0%) | |||
| Facial pain | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Fatigue | 108/236 (45.8%) | 49/99 (49.5%) | 60/116 (51.7%) | |||
| Fever | 17/236 (7.2%) | 9/99 (9.1%) | 21/116 (18.1%) | |||
| Flu like symptoms | 7/236 (3%) | 10/99 (10.1%) | 10/116 (8.6%) | |||
| Gait disturbance | 2/236 (0.8%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Infusion related reaction | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Injection site reaction | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Irritability | 2/236 (0.8%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Localized edema | 2/236 (0.8%) | 7/99 (7.1%) | 5/116 (4.3%) | |||
| Malaise | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Muscle cramps | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Night sweats | 2/236 (0.8%) | 0/99 (0%) | 4/116 (3.4%) | |||
| Non-cardiac chest pain | 4/236 (1.7%) | 1/99 (1%) | 7/116 (6%) | |||
| Pain | 32/236 (13.6%) | 33/99 (33.3%) | 45/116 (38.8%) | |||
| Sweating | 1/236 (0.4%) | 2/99 (2%) | 4/116 (3.4%) | |||
| Tongue sensitivity | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Gallbladder fistula | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Gallbladder obstruction | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Gallbladder pain | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Liver abscess | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Immune system disorders | ||||||
| Allergic reaction | 0/236 (0%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Anaphylaxis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Lymphadenopathy | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Seasonal allergies | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Tongue swelling | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Infections and infestations | ||||||
| Bladder infection | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Bronchial infection | 0/236 (0%) | 4/99 (4%) | 5/116 (4.3%) | |||
| C. difficile infection | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| Ear infection | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Ehrlichiosis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Eye infection | 0/236 (0%) | 0/99 (0%) | 0/116 (0%) | |||
| Foot infection | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Gum infection | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| HSV infection (oral) | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Infected cyst | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Infected sebaceous cyst | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Laryngitis | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Lung infection | 4/236 (1.7%) | 2/99 (2%) | 8/116 (6.9%) | |||
| Mucosal infection | 3/236 (1.3%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Nail infection | 1/236 (0.4%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Otitis media | 1/236 (0.4%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Papulopustular rash | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Parasitic infection NOS | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Paronychia | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| Peripheral nerve infection | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Pharyngitis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Pleural infection | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Rash pustular | 2/236 (0.8%) | 2/99 (2%) | 0/116 (0%) | |||
| Roseola | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Shingles | 1/236 (0.4%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Sinusitis | 4/236 (1.7%) | 5/99 (5.1%) | 5/116 (4.3%) | |||
| Skin infection | 5/236 (2.1%) | 3/99 (3%) | 7/116 (6%) | |||
| Skin wound NOS | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Small intestine infection | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Soft tissue infection | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Sunburn | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Testicular infection | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Tongue laceration | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Tooth infection | 1/236 (0.4%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Upper respiratory infection | 72/236 (30.5%) | 34/99 (34.3%) | 54/116 (46.6%) | |||
| Urinary tract infection | 7/236 (3%) | 4/99 (4%) | 6/116 (5.2%) | |||
| Vaginal infection | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Viral infection-NOS | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Yeast infection | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Injury, poisoning and procedural complications | ||||||
| Bruising | 7/236 (3%) | 7/99 (7.1%) | 8/116 (6.9%) | |||
| Burn | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Burn from chemical peel | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Dog bite | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Fall | 5/236 (2.1%) | 7/99 (7.1%) | 7/116 (6%) | |||
| Fracture | 3/236 (1.3%) | 1/99 (1%) | 0/116 (0%) | |||
| Hernia | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Patellar dislocation | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Tick bite | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Investigations | ||||||
| Activated partial thromboplastin time prolonged | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Activated partial thromboplastin time prolonged | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Alanine aminotransferase increased | 39/236 (16.5%) | 11/99 (11.1%) | 28/116 (24.1%) | |||
| Alkaline phosphatase increased | 18/236 (7.6%) | 7/99 (7.1%) | 16/116 (13.8%) | |||
| Aspartate aminotransferase increased | 29/236 (12.3%) | 12/99 (12.1%) | 25/116 (21.6%) | |||
| Blood bilirubin increased | 7/236 (3%) | 4/99 (4%) | 5/116 (4.3%) | |||
| Cholesterol high | 0/236 (0%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Creatinine increased | 35/236 (14.8%) | 18/99 (18.2%) | 22/116 (19%) | |||
| Fibrinogen decreased | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| GGT increased | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| INR increased | 0/236 (0%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Lipase increased | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Lymphocyte count decreased | 144/236 (61%) | 48/99 (48.5%) | 59/116 (50.9%) | |||
| Lymphocyte count increased | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Neutrophil count decreased | 64/236 (27.1%) | 17/99 (17.2%) | 84/116 (72.4%) | |||
| Platelet count decreased | 97/236 (41.1%) | 36/99 (36.4%) | 54/116 (46.6%) | |||
| Prostate specific antigen increased | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Serum amylase increased | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Transminitis NOS | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Vitamin B12 deficiency | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Vitamin D deficiency | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Weight gain | 8/236 (3.4%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Weight loss | 1/236 (0.4%) | 3/99 (3%) | 4/116 (3.4%) | |||
| White blood cell decreased | 104/236 (44.1%) | 27/99 (27.3%) | 67/116 (57.8%) | |||
| Metabolism and nutrition disorders | ||||||
| Anorexia | 5/236 (2.1%) | 3/99 (3%) | 11/116 (9.5%) | |||
| Dehydration | 3/236 (1.3%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Hypercalcemia | 6/236 (2.5%) | 7/99 (7.1%) | 4/116 (3.4%) | |||
| Hyperglycemia | 80/236 (33.9%) | 23/99 (23.2%) | 33/116 (28.4%) | |||
| Hyperkalemia | 8/236 (3.4%) | 8/99 (8.1%) | 8/116 (6.9%) | |||
| Hypermagnesemia | 2/236 (0.8%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hypernatremia | 15/236 (6.4%) | 6/99 (6.1%) | 9/116 (7.8%) | |||
| Hypertriglyceridemia | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Hyperuricemia | 4/236 (1.7%) | 4/99 (4%) | 4/116 (3.4%) | |||
| Hypoalbuminemia | 23/236 (9.7%) | 1/99 (1%) | 4/116 (3.4%) | |||
| Hypocalcemia | 30/236 (12.7%) | 5/99 (5.1%) | 18/116 (15.5%) | |||
| Hypoglycemia | 15/236 (6.4%) | 7/99 (7.1%) | 14/116 (12.1%) | |||
| Hypokalemia | 30/236 (12.7%) | 9/99 (9.1%) | 30/116 (25.9%) | |||
| Hypomagnesemia | 3/236 (1.3%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Hyponatremia | 14/236 (5.9%) | 2/99 (2%) | 6/116 (5.2%) | |||
| Hypophosphatemia | 6/236 (2.5%) | 2/99 (2%) | 2/116 (1.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Achilles tendinosis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Arthralgia | 11/236 (4.7%) | 11/99 (11.1%) | 21/116 (18.1%) | |||
| Arthritis | 3/236 (1.3%) | 10/99 (10.1%) | 9/116 (7.8%) | |||
| Avascular necrosis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Back pain | 58/236 (24.6%) | 34/99 (34.3%) | 57/116 (49.1%) | |||
| Bone pain | 10/236 (4.2%) | 12/99 (12.1%) | 12/116 (10.3%) | |||
| Bone spur | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Chest wall pain | 7/236 (3%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Fibromyalgia | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Flank pain | 8/236 (3.4%) | 3/99 (3%) | 7/116 (6%) | |||
| Generalized muscle weakness | 4/236 (1.7%) | 4/99 (4%) | 3/116 (2.6%) | |||
| Gout | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Hernia | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Joint range of motion decreased | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Meniscus tear | 1/236 (0.4%) | 1/99 (1%) | 0/116 (0%) | |||
| Muscle cramping | 10/236 (4.2%) | 5/99 (5.1%) | 23/116 (19.8%) | |||
| Muscle weakness (thumb) | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Muscle weakness left-sided | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Muscle weakness lower limb | 3/236 (1.3%) | 1/99 (1%) | 0/116 (0%) | |||
| Muscle weakness trunk | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Muscle weakness upper limb | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Myalgia | 18/236 (7.6%) | 14/99 (14.1%) | 28/116 (24.1%) | |||
| Neck pain | 4/236 (1.7%) | 6/99 (6.1%) | 13/116 (11.2%) | |||
| Osteonecrosis of jaw | 0/236 (0%) | 2/99 (2%) | 0/116 (0%) | |||
| Osteoporosis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Pain in extremity | 30/236 (12.7%) | 29/99 (29.3%) | 30/116 (25.9%) | |||
| Rhabdomyolysis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Temporomandibular joint syndrome | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Benign polyp | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Boil | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Breast lump | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Cyst | 1/236 (0.4%) | 1/99 (1%) | 5/116 (4.3%) | |||
| Lump NOS | 0/236 (0%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Nodule | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Non-melanoma skin cancer | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Plasmacytoma (myeloma progression) | 1/236 (0.4%) | 4/99 (4%) | 2/116 (1.7%) | |||
| Pulmonary nodule | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Seborrheic keratosis | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Thyroid nodule | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Nervous system disorders | ||||||
| Amnesia | 0/236 (0%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Dizziness | 19/236 (8.1%) | 9/99 (9.1%) | 15/116 (12.9%) | |||
| Dysarthria | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Dysgeusia | 17/236 (7.2%) | 2/99 (2%) | 6/116 (5.2%) | |||
| Dystonic reaction | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Facial nerve disorder | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Foot drop | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Headache | 23/236 (9.7%) | 8/99 (8.1%) | 21/116 (18.1%) | |||
| Hypersomnia | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Left-sided numbness | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Memory impairment | 1/236 (0.4%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Movements involuntary | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Muscle cramping | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Neuralgia | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Pain in extremity | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Paresthesia | 9/236 (3.8%) | 6/99 (6.1%) | 11/116 (9.5%) | |||
| Parkinsonism | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Peripheral motor neuropathy | 12/236 (5.1%) | 9/99 (9.1%) | 11/116 (9.5%) | |||
| Peripheral sensory neuropathy | 89/236 (37.7%) | 48/99 (48.5%) | 65/116 (56%) | |||
| Phantom pain | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Presyncope | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| Seizure | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Spinal stenosis | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Syncope | 3/236 (1.3%) | 2/99 (2%) | 0/116 (0%) | |||
| Tardive dyskinesia | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Tremor | 6/236 (2.5%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Twitching | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Psychiatric disorders | ||||||
| Agitation | 10/236 (4.2%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Anxiety | 11/236 (4.7%) | 4/99 (4%) | 10/116 (8.6%) | |||
| Confusion | 2/236 (0.8%) | 3/99 (3%) | 3/116 (2.6%) | |||
| Delirium | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Depression | 11/236 (4.7%) | 7/99 (7.1%) | 9/116 (7.8%) | |||
| Hallucinations | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Insomnia | 59/236 (25%) | 10/99 (10.1%) | 17/116 (14.7%) | |||
| Psychosocial difficulties | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Recurrent dreams | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Restlessness | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/236 (0%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Bladder stones | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Chronic kidney disease | 0/236 (0%) | 1/99 (1%) | 4/116 (3.4%) | |||
| Cystitis noninfective | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hematuria | 1/236 (0.4%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Kidney stones | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| Proteinuria | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Renal calculi | 3/236 (1.3%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Urinary frequency | 5/236 (2.1%) | 3/99 (3%) | 2/116 (1.7%) | |||
| Urinary incontinence | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Urinary retention | 2/236 (0.8%) | 2/99 (2%) | 0/116 (0%) | |||
| Urinary tract pain | 1/236 (0.4%) | 4/99 (4%) | 4/116 (3.4%) | |||
| Urinary urgency | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Urostomy obstruction | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Cystocele | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Erectile dysfunction | 1/236 (0.4%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Nipple pain | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Penile pain | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Premenstrual syndrome | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Prostate pain | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Prostatic obstruction | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Vaginal dryness | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Vaginal hemorrhage | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| Vaginal pain | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Allergic rhinitis | 8/236 (3.4%) | 8/99 (8.1%) | 4/116 (3.4%) | |||
| Aspiration | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Asthma | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| COPD exacerbation | 1/236 (0.4%) | 1/99 (1%) | 0/116 (0%) | |||
| Cough | 36/236 (15.3%) | 25/99 (25.3%) | 46/116 (39.7%) | |||
| Dyspnea | 32/236 (13.6%) | 19/99 (19.2%) | 27/116 (23.3%) | |||
| Epistaxis | 5/236 (2.1%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hemoptysis | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Hiccups | 8/236 (3.4%) | 2/99 (2%) | 1/116 (0.9%) | |||
| Hoarseness | 3/236 (1.3%) | 1/99 (1%) | 3/116 (2.6%) | |||
| Hypoxia | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Laryngeal inflammation | 0/236 (0%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Nasal congestion | 16/236 (6.8%) | 8/99 (8.1%) | 20/116 (17.2%) | |||
| Nasal nares inflammation | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Pneumonitis | 1/236 (0.4%) | 2/99 (2%) | 3/116 (2.6%) | |||
| Postnasal drip | 4/236 (1.7%) | 5/99 (5.1%) | 8/116 (6.9%) | |||
| Productive cough | 11/236 (4.7%) | 3/99 (3%) | 8/116 (6.9%) | |||
| Pulmonary edema | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Sinus disorder | 0/236 (0%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Sleep apnea | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Sneezing | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Sore throat | 11/236 (4.7%) | 5/99 (5.1%) | 6/116 (5.2%) | |||
| Wheezing | 4/236 (1.7%) | 0/99 (0%) | 3/116 (2.6%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Actinic keratosis | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Allergic contact dermatitis | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Alopecia | 1/236 (0.4%) | 2/99 (2%) | 0/116 (0%) | |||
| Brittle nails | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Bullous dermatitis | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Chalazion | 1/236 (0.4%) | 2/99 (2%) | 0/116 (0%) | |||
| Chapped lips | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Dry skin | 18/236 (7.6%) | 4/99 (4%) | 17/116 (14.7%) | |||
| Eczema | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Erythema multiforme | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Hyperhidrosis | 2/236 (0.8%) | 0/99 (0%) | 4/116 (3.4%) | |||
| Hypohidrosis | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Ingrown toenail | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Nail discoloration | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Nail ridging | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Nevi (benign) | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Pain of skin | 1/236 (0.4%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Palmar-plantar erythrodysesthesia syndrome | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Petechiae | 1/236 (0.4%) | 1/99 (1%) | 0/116 (0%) | |||
| Photosensitivity | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Poison ivy | 2/236 (0.8%) | 0/99 (0%) | 0/116 (0%) | |||
| Pruritus | 8/236 (3.4%) | 6/99 (6.1%) | 7/116 (6%) | |||
| Rash NOS | 0/236 (0%) | 1/99 (1%) | 2/116 (1.7%) | |||
| Rash acneiform | 1/236 (0.4%) | 2/99 (2%) | 2/116 (1.7%) | |||
| Rash maculo-papular | 33/236 (14%) | 24/99 (24.2%) | 27/116 (23.3%) | |||
| Rosacea | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Skin hyperpigmentation | 2/236 (0.8%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Skin hypersensitiviy | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Skin laceration | 0/236 (0%) | 3/99 (3%) | 0/116 (0%) | |||
| Skin lesion NOS | 0/236 (0%) | 3/99 (3%) | 3/116 (2.6%) | |||
| Skin tear NOS | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Skin ulceration | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Urticaria | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Wart | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Surgical and medical procedures | ||||||
| Arthroscopy of knee | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Crown dislodged | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Foot surgery | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Hernia repair | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Left orthopedic repair/surgery | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Oral surgery | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Orthopedic repair/surgery NOS | 0/236 (0%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Root canal | 0/236 (0%) | 1/99 (1%) | 1/116 (0.9%) | |||
| Spine surgery | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Tooth extraction | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Vascular disorders | ||||||
| Flushing | 6/236 (2.5%) | 1/99 (1%) | 0/116 (0%) | |||
| Hematoma | 0/236 (0%) | 0/99 (0%) | 2/116 (1.7%) | |||
| Hot flashes | 7/236 (3%) | 6/99 (6.1%) | 11/116 (9.5%) | |||
| Hypertension | 34/236 (14.4%) | 18/99 (18.2%) | 25/116 (21.6%) | |||
| Hyperviscosity | 0/236 (0%) | 1/99 (1%) | 0/116 (0%) | |||
| Hypotension | 10/236 (4.2%) | 3/99 (3%) | 4/116 (3.4%) | |||
| Lymphedema | 1/236 (0.4%) | 0/99 (0%) | 1/116 (0.9%) | |||
| Superficial thrombophlebitis | 1/236 (0.4%) | 0/99 (0%) | 0/116 (0%) | |||
| Thromboembolic event | 4/236 (1.7%) | 1/99 (1%) | 7/116 (6%) | |||
| Vascular calcification | 0/236 (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/Title | Ravi Vij, M.D. |
|---|---|
| Organization | Washington University School of Medicine |
| Phone | 314-454-8323 |
| rvij@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:
Jul 12, 2022
Last Verified:
Jul 1, 2022