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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00689936




Registration number
NCT00689936
Ethics application status
Date submitted
2/06/2008
Date registered
4/06/2008
Date last updated
20/11/2019

Titles & IDs
Public title
Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma
Scientific title
A Phase III, Randomized, Open-label, 3-arm Study to Determine the Efficacy and Safety of Lenalidomide(REVLIMID) Plus Low-dose Dexamethasone When Given Until Progressive Disease or for 18 Four-week Cycles Versus the Combination of Melphalan, Prednisone, and Thalidomide Given for 12 Six-week Cycles in Patients With Previously Untreated Multiple Myeloma Who Are Either 65 Years of Age or Older or Not Candidates for Stem Cell Transplantation.
Secondary ID [1] 0 0
2007-004823-39
Secondary ID [2] 0 0
CC-5013-MM-020
Universal Trial Number (UTN)
Trial acronym
FIRST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenalidomide and low-dose dexamethasone
Treatment: Drugs - Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles
Treatment: Drugs - Melphalan, Prednisone and Thalidomide

Experimental: Lenalidomide / Dexamethasone until disease progression - Lenalidomide plus low-dose dexamethasone given until disease progression

Experimental: Lenalidomide / Dexamethasone for 18 cycles - Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles

Active Comparator: Melphalan, Prednisone, and Thalidomide (MPT) for 12 cycles - Combination of Melphalan, Prednisone and Thalidomide given for 12 six-week cycles


Treatment: Drugs: Lenalidomide and low-dose dexamethasone
Lenalidomide - oral, 2.5mg, 5mg, 10mg, 15mg 20mg, or 25 mg capsules, given either days 1-21 of each 28 day cycles or given every other day for 21 days until documentation of PD.
Dexamethasone - oral 4mg tablets for a total dose of 20mg or 40 mg given days 1,8,15 and 22 of each 28 day cycle up to disease progression

Treatment: Drugs: Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles
lenalidomide - oral, 2.5mg, 5mg, 10mg, 15mg, 20 mg or 25 mg capsules given on days 1-21 of each 28 day cycle or every other day for 21 days for 18 cycles.
Dexamethasone - oral 4mg tablets for a total dose of 20mg or 40 mg given days 1,8,15 and 22 of each 28 day cycle for 18 cycles

Treatment: Drugs: Melphalan, Prednisone and Thalidomide
Melphalan - oral, 2mg tablets dosed at either 0.25mg/kg, 0.125 mg/kg, 0.20mg/kg or 0.10mg/kg on days 1-4 of each 42 day cycle up to 12 cycles Prednisone - oral, 5mg, 10mg, 20 mg and 50 mg tablets dosed at 2mg/kg daily days 1-4 of each 42 day cycle for up to 12 cycles Thalidomide - oral, 50mg, 100mg and 200 mg capsules dosed at either 100mg or 200 mg daily on days 1-41 of each 42 day cycle for up to 12 cycles

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC) - PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).
Timepoint [1] 0 0
From date of randomization until the data cut-off date of 24 May 2013. Median follow-up time for all participants was 17.1 months.
Primary outcome [2] 0 0
Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis - PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).
Timepoint [2] 0 0
From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months
Secondary outcome [1] 0 0
Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS) - Overall survival was defined as the time between randomization and death. Participants, who died, regardless of the cause of death, were considered to have had an event. All participants who were lost to follow-up prior to the end of the trial or who were withdrawn from the trial were censored at the time of last contact. Participants who were still being treated were censored at the last available date the participant was known to be alive.
Timepoint [1] 0 0
From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 48.3 months
Secondary outcome [2] 0 0
Percentage of Participants With an Objective Response Based on IRAC Review - Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined as: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [2] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [3] 0 0
Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis - Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [3] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [4] 0 0
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC - Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.
Timepoint [4] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median follow-up for responders was 20.1 months
Secondary outcome [5] 0 0
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis - Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.
Timepoint [5] 0 0
Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median follow-up for responders was 19.9 months
Secondary outcome [6] 0 0
Time to First Response Based on the Review by the IRAC - The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria.
Timepoint [6] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [7] 0 0
Time to First Response Based on the Investigator Assessment at the Time of Final Analysis - The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria assessed by the investigator.
Timepoint [7] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm.
Secondary outcome [8] 0 0
Kaplan Meier Estimates of Time to Treatment Failure (TTF) - TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by IRAC based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.
Timepoint [8] 0 0
From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months.
Secondary outcome [9] 0 0
Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis - TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by the investigators assessment based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.
Timepoint [9] 0 0
From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months.
Secondary outcome [10] 0 0
Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT) - Time to second-line anti-myeloma therapy was defined as time from randomization to the start of another non-protocol anti-myeloma therapy.
Timepoint [10] 0 0
From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months
Secondary outcome [11] 0 0
Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis - Time to second-line anti-myeloma therapy is defined as time from randomization to the start of another non-protocol anti-myeloma therapy. Those who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.
Timepoint [11] 0 0
From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months
Secondary outcome [12] 0 0
Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis - Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [12] 0 0
Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [13] 0 0
Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review. - Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [13] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [14] 0 0
Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review - Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [14] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [15] 0 0
Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review - Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [15] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [16] 0 0
Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review - Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.
Timepoint [16] 0 0
Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [17] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.
Timepoint [17] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [18] 0 0
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Timepoint [18] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [19] 0 0
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Timepoint [19] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [20] 0 0
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Timepoint [20] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [21] 0 0
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Timepoint [21] 0 0
Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [22] 0 0
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Timepoint [22] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [23] 0 0
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Timepoint [23] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation
Secondary outcome [24] 0 0
Change From Baseline in the EORTC QLQ-C30 Pain Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Timepoint [24] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [25] 0 0
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Timepoint [25] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [26] 0 0
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Timepoint [26] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [27] 0 0
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Timepoint [27] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [28] 0 0
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Scale is scored between 0 and 100, with a high score indicating a higher level of appetite loss. Negative change from Baseline values indicate improvement in appetite and positive values indicate worsening of appetite.
Timepoint [28] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [29] 0 0
Change From Baseline in the EORTC QLQ-C30 Constipation Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale is scored between 0 and 100, with a high score indicating a higher level of constipation. Negative change from Baseline values indicate improvement in constipation and positive values indicate worsening of constipation.
Timepoint [29] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [30] 0 0
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100, with a high score indicating a higher level of diarrhea. Negative change from Baseline values indicate improvement in diarrhea and positive values indicate worsening of diarrhea.
Timepoint [30] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [31] 0 0
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain - The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Difficulties Scale is scored between 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicate improvement in financial difficulties and positive values indicate worsening of financial difficulties.
Timepoint [31] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [32] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale - EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score indicates more severe disease symptom(s).
Timepoint [32] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [33] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale - EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment.
Timepoint [33] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [34] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale - EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future.
Timepoint [34] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [35] 0 0
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale - EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the body image scale, a higher score indicates a better body image.
Timepoint [35] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [36] 0 0
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score - EQ-5D is a self-administered questionnaire that assesses health-related quality of life. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where higher EQ-5D scores represent better health status. A positive change from baseline score indicates improvement in health status and better health state.
Timepoint [36] 0 0
Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary outcome [37] 0 0
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year - HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of inpatient hospitalizations per patient year was calculated as the total number of hospitalizations divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.
Timepoint [37] 0 0
Day 1 (randomization) up to last visit completed 25 July 2016
Secondary outcome [38] 0 0
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase - A TEAE is any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event.
Timepoint [38] 0 0
From first dose of study drug through 28 days following the discontinuation visit from active treatment phase; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [39] 0 0
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase - Renal function was assessed for participants from baseline to the most extreme value in creatinine clearance calculated using the Cockcroft-Gault estimation.
Timepoint [39] 0 0
Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [40] 0 0
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase - Neutrophil counts was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.
Timepoint [40] 0 0
Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [41] 0 0
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase - Hemoglobin was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.
Timepoint [41] 0 0
Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [42] 0 0
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. - Improvement in platelets was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.
Timepoint [42] 0 0
Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary outcome [43] 0 0
Improvement of Infection Rate by Observing the Historical Data Compared to the Clinical Data Base - Improvement of infection rate by observing historical data compared to the data within clinical database as not analyzed.
Timepoint [43] 0 0
From randomization to 24 May 2013

Eligibility
Key inclusion criteria
1. Must understand and voluntarily sign informed consent form

2. Age = 18 years at the time of signing consent

3. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:

- MM diagnostic criteria (all 3 required):

- Monoclonal plasma cells in the bone marrow =10% and/or presence of a
biopsy-proven plasmacytoma

- Monoclonal protein present in the serum and/or urine

- Myeloma-related organ dysfunction (at least one of the following) [C] Calcium
elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R]
Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl
or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis

AND have measurable disease by protein electrophoresis analyses as defined by the
following:

- IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level = 1.0 g/dl
or urine M-protein level = 200 mg/24 hours

- IgA multiple myeloma: Serum M-protein level = 0.5 g/dl or urine M-protein level =
200 mg/24 hours

- IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by
skeletal survey plain films): Serum M-protein level = 1.0 g/dl or urine M-protein
level = 200mg/24hours

- IgD multiple myeloma: Serum M-protein level = 0.05 g/dl or urine M-protein level
= 200 mg/24 hours

- Light chain multiple myeloma: Serum M-protein level = 1.0 g/dl or urine M-protein
level = 200 mg/24 hours

AND are at least 65 years of age or older or, if younger than 65 years of age, are not
candidates for stem cell transplantation because:

- The patient declines to undergo stem cell transplantation or

- Stem cell transplantation is not available to the patient due to cost or other
reasons

4. ECOG performance status of 0, 1, or 2

5. Able to adhere to the study visit schedule and other protocol requirements

6. Females of child-bearing potential (FCBP)^2:

1. Must agree to undergo two medically supervised pregnancy tests prior to starting
study therapy with either Rd or MPT. The first pregnancy test will be performed
within 10-14 days prior to the start of Rd or MPT and the second pregnancy test
will be performed within 24 hours prior to the start of Rd or MPT. She must also
agree to ongoing pregnancy testing during the course of the study and after the
end of study therapy. This applies even if the patient practices complete and
continued sexual abstinence.

2. Must commit to either continued abstinence from heterosexual intercourse (which
must be reviewed on a monthly basis) or agree to use and be able to comply with
effective contraception without interruption, 28 days prior to starting study
drug, during the study therapy (including during periods of dose interruptions),
and for 28 days after discontinuation of study therapy.

7. Male Patients:

1. Must agree to use a condom during sexual contact with a FCBP, even if they have
had a vasectomy, throughout study drug therapy, during any dose interruption and
after cessation of study therapy.

2. Must agree to not donate semen during study drug therapy and for a period after
end of study drug therapy.

3. Must practice complete abstinence or agree to use a condom during sexual contact
with a pregnant female or a female of childbearing potential while participating
in the study, during dose interruptions and for at least 28 days following study
drug discontinuation, even if he has undergone a successful vasectomy.

8. All patients must:

1. Have an understanding that the study drug could have a potential teratogenic
risk.

2. Agree to abstain from donating blood while taking study drug therapy and
following discontinuation of study drug therapy.

3. Agree not to share study medication with another person. All FCBP and male
patients must be counseled about pregnancy precautions and risks of fetal
exposure.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous treatment with anti-myeloma therapy (does not include radiotherapy,
bisphosphonates, or a single short course of steroid [i.e., less than or equal to the
equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid
treatment must not have been given within 14 days of randomization]).

2. Any serious medical condition that places the patient at an unacceptable risk if he or
she participates in this study. Examples of such a medical condition are, but are not
limited to, patient with unstable cardiac disease as defined by: Cardiac events such
as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial
fibrillation or hypertension; patients with conditions requiring chronic steroid or
immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and
lupus, that likely need additional steroid or immunosuppressive treatments in addition
to the study treatment.

3. Pregnant or lactating females.

4. Any of the following laboratory abnormalities:

- Absolute neutrophil count (ANC) < 1,000/µL (1.0 x 109/L)

- Untransfused platelet count < 50,000 cells/µL (50 x 10^9/L)

- Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)

5. Renal failure requiring hemodialysis or peritoneal dialysis.

6. Prior history of malignancies, other than multiple myeloma, unless the patient has
been free of the disease for = 3 years. Exceptions include the following:

- Basal cell carcinoma of the skin

- Squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix

- Carcinoma in situ of the breast

- Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)

7. Patients who are unable or unwilling to undergo antithrombotic therapy.

8. Peripheral neuropathy of > grade 2 severity.

9. Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL
(immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.

- 1 A variety of other types of end organ dysfunctions can occasionally occur and
lead to a need for therapy. Such dysfunction is sufficient to support
classification as myeloma if proven to be myeloma-related.

- 2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or
bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e.,
amenorrhea following cancer therapy does not rule out childbearing potential) for
at least 24 consecutive months (i.e., has had menses at any time in the preceding
24 consecutive months).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology - E. Melbourne
Recruitment hospital [3] 0 0
Western Hospital - Footscray
Recruitment hospital [4] 0 0
Frankston Hospital - Frankston
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
Geelong Hospital - Geelong
Recruitment hospital [7] 0 0
Gosford Hospital - Gosford
Recruitment hospital [8] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [9] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [10] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [11] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [12] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [13] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [14] 0 0
Westmead Hospital - Wentworthville
Recruitment hospital [15] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [16] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [17] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3002 - E. Melbourne
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment postcode(s) [7] 0 0
2250 - Gosford
Recruitment postcode(s) [8] 0 0
4029 - Herston
Recruitment postcode(s) [9] 0 0
3144 - Malvern
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment postcode(s) [11] 0 0
6000 - Perth
Recruitment postcode(s) [12] 0 0
4215 - Southport
Recruitment postcode(s) [13] 0 0
2065 - St Leonards
Recruitment postcode(s) [14] 0 0
2145 - Wentworthville
Recruitment postcode(s) [15] 0 0
3690 - Wodonga
Recruitment postcode(s) [16] 0 0
2500 - Wollongong
Recruitment postcode(s) [17] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Maine
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Montana
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Dakota
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Austria
State/province [18] 0 0
Leoben
Country [19] 0 0
Austria
State/province [19] 0 0
Linz
Country [20] 0 0
Austria
State/province [20] 0 0
Salzburg
Country [21] 0 0
Austria
State/province [21] 0 0
St. Pölten
Country [22] 0 0
Austria
State/province [22] 0 0
Vienna
Country [23] 0 0
Austria
State/province [23] 0 0
Wels
Country [24] 0 0
Austria
State/province [24] 0 0
Wiener Neustadt
Country [25] 0 0
Belgium
State/province [25] 0 0
Antwerpen
Country [26] 0 0
Belgium
State/province [26] 0 0
Arlon
Country [27] 0 0
Belgium
State/province [27] 0 0
Brugge
Country [28] 0 0
Belgium
State/province [28] 0 0
Brussels
Country [29] 0 0
Belgium
State/province [29] 0 0
Brussel
Country [30] 0 0
Belgium
State/province [30] 0 0
Bruxelles
Country [31] 0 0
Belgium
State/province [31] 0 0
Edegem
Country [32] 0 0
Belgium
State/province [32] 0 0
Gent
Country [33] 0 0
Belgium
State/province [33] 0 0
Hasselt
Country [34] 0 0
Belgium
State/province [34] 0 0
Leuven
Country [35] 0 0
Belgium
State/province [35] 0 0
Roeselare
Country [36] 0 0
Belgium
State/province [36] 0 0
Yvoir
Country [37] 0 0
Canada
State/province [37] 0 0
Alberta
Country [38] 0 0
Canada
State/province [38] 0 0
British Columbia
Country [39] 0 0
Canada
State/province [39] 0 0
New Brunswick
Country [40] 0 0
Canada
State/province [40] 0 0
Nova Scotia
Country [41] 0 0
Canada
State/province [41] 0 0
Ontario
Country [42] 0 0
Canada
State/province [42] 0 0
Quebec
Country [43] 0 0
China
State/province [43] 0 0
Beijing
Country [44] 0 0
China
State/province [44] 0 0
Chengdu
Country [45] 0 0
China
State/province [45] 0 0
Shanghai
Country [46] 0 0
China
State/province [46] 0 0
Tianjin
Country [47] 0 0
France
State/province [47] 0 0
Albi
Country [48] 0 0
France
State/province [48] 0 0
Amiens
Country [49] 0 0
France
State/province [49] 0 0
Angers cedex 01
Country [50] 0 0
France
State/province [50] 0 0
Argenteuil
Country [51] 0 0
France
State/province [51] 0 0
Bayonne
Country [52] 0 0
France
State/province [52] 0 0
Blois cedex
Country [53] 0 0
France
State/province [53] 0 0
Bobigny Cedex
Country [54] 0 0
France
State/province [54] 0 0
Bordeaux
Country [55] 0 0
France
State/province [55] 0 0
Bourg en Bresse cedex
Country [56] 0 0
France
State/province [56] 0 0
Brest cedex
Country [57] 0 0
France
State/province [57] 0 0
Caen cedex 5
Country [58] 0 0
France
State/province [58] 0 0
Caen
Country [59] 0 0
France
State/province [59] 0 0
Cannes Cedex
Country [60] 0 0
France
State/province [60] 0 0
Cergy-Pontoise
Country [61] 0 0
France
State/province [61] 0 0
Chalon/Saone Cedex
Country [62] 0 0
France
State/province [62] 0 0
Clamart Cedex
Country [63] 0 0
France
State/province [63] 0 0
Clamart
Country [64] 0 0
France
State/province [64] 0 0
Clermont Ferrand
Country [65] 0 0
France
State/province [65] 0 0
Colmar cedex
Country [66] 0 0
France
State/province [66] 0 0
Creteil
Country [67] 0 0
France
State/province [67] 0 0
Dijon
Country [68] 0 0
France
State/province [68] 0 0
Dunkerque
Country [69] 0 0
France
State/province [69] 0 0
Grenoble cedex 09
Country [70] 0 0
France
State/province [70] 0 0
Grenoble
Country [71] 0 0
France
State/province [71] 0 0
La Roche -Sur-Yon cedex 9
Country [72] 0 0
France
State/province [72] 0 0
Le Chesnay Cedex
Country [73] 0 0
France
State/province [73] 0 0
Le Havre
Country [74] 0 0
France
State/province [74] 0 0
Le Kremlin bicetre CDX
Country [75] 0 0
France
State/province [75] 0 0
Le Mans cedex
Country [76] 0 0
France
State/province [76] 0 0
Le Mans
Country [77] 0 0
France
State/province [77] 0 0
Lille cedex
Country [78] 0 0
France
State/province [78] 0 0
Lille
Country [79] 0 0
France
State/province [79] 0 0
Limoges Cedex 1
Country [80] 0 0
France
State/province [80] 0 0
Lyon cedex
Country [81] 0 0
France
State/province [81] 0 0
Lyon
Country [82] 0 0
France
State/province [82] 0 0
Marseille Cedex 9
Country [83] 0 0
France
State/province [83] 0 0
METZ cedex 3
Country [84] 0 0
France
State/province [84] 0 0
Montauban cedex
Country [85] 0 0
France
State/province [85] 0 0
Montpellier Cedex 5
Country [86] 0 0
France
State/province [86] 0 0
Mulhouse
Country [87] 0 0
France
State/province [87] 0 0
Nantes
Country [88] 0 0
France
State/province [88] 0 0
Nice cedex 1
Country [89] 0 0
France
State/province [89] 0 0
Nice cedex 3
Country [90] 0 0
France
State/province [90] 0 0
Orleans
Country [91] 0 0
France
State/province [91] 0 0
Paris Cedex 14
Country [92] 0 0
France
State/province [92] 0 0
Paris
Country [93] 0 0
France
State/province [93] 0 0
Pessac
Country [94] 0 0
France
State/province [94] 0 0
Poitiers cedex
Country [95] 0 0
France
State/province [95] 0 0
Reims cedex
Country [96] 0 0
France
State/province [96] 0 0
Reims
Country [97] 0 0
France
State/province [97] 0 0
Rennes cedex 02
Country [98] 0 0
France
State/province [98] 0 0
Rennes Cedex
Country [99] 0 0
France
State/province [99] 0 0
Rodez
Country [100] 0 0
France
State/province [100] 0 0
Rouen cedex
Country [101] 0 0
France
State/province [101] 0 0
Saint Cloud
Country [102] 0 0
France
State/province [102] 0 0
St Priest en Jarez
Country [103] 0 0
France
State/province [103] 0 0
St-Brieuc cedex 1
Country [104] 0 0
France
State/province [104] 0 0
Strasbourg
Country [105] 0 0
France
State/province [105] 0 0
Toulouse cedex 9
Country [106] 0 0
France
State/province [106] 0 0
Tours cedex
Country [107] 0 0
France
State/province [107] 0 0
Tours
Country [108] 0 0
France
State/province [108] 0 0
Vandoeuvre Cedex
Country [109] 0 0
France
State/province [109] 0 0
Vannes cedex
Country [110] 0 0
France
State/province [110] 0 0
Villejuif
Country [111] 0 0
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose
dexamethasone to that of the combination of melphalan, prednisone and thalidomide.
Trial website
https://clinicaltrials.gov/show/NCT00689936
Trial related presentations / publications
Dimopoulos MA, Cheung MC, Roussel M, Liu T, Gamberi B, Kolb B, Derigs HG, Eom H, Belhadj K, Lenain P, Van der Jagt R, Rigaudeau S, Dib M, Hall R, Jardel H, Jaccard A, Tosikyan A, Karlin L, Bensinger W, Schots R, Leupin N, Chen G, Marek J, Ervin-Haynes A, Facon T. Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma. Haematologica. 2016 Mar;101(3):363-70. doi: 10.3324/haematol.2015.133629. Epub 2015 Dec 11.
Hulin C, Belch A, Shustik C, Petrucci MT, Dührsen U, Lu J, Song K, Rodon P, Pégourié B, Garderet L, Hunter H, Azais I, Eek R, Gisslinger H, Macro M, Dakhil S, Goncalves C, LeBlanc R, Romeril K, Royer B, Doyen C, Leleu X, Offner F, Leupin N, Houck V, Chen G, Ervin-Haynes A, Dimopoulos MA, Facon T. Updated Outcomes and Impact of Age With Lenalidomide and Low-Dose Dexamethasone or Melphalan, Prednisone, and Thalidomide in the Randomized, Phase III FIRST Trial. J Clin Oncol. 2016 Oct 20;34(30):3609-3617. doi: 10.1200/JCO.2016.66.7295.
Delforge M, Minuk L, Eisenmann JC, Arnulf B, Canepa L, Fragasso A, Leyvraz S, Langer C, Ezaydi Y, Vogl DT, Giraldo-Castellano P, Yoon SS, Zarnitsky C, Escoffre-Barbe M, Lemieux B, Song K, Bahlis NJ, Guo S, Monzini MS, Ervin-Haynes A, Houck V, Facon T. Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide. Haematologica. 2015 Jun;100(6):826-33. doi: 10.3324/haematol.2014.120121. Epub 2015 Mar 13.
Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, Van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014 Sep 4;371(10):906-17. doi: 10.1056/NEJMoa1402551.
Vogl DT, Delforge M, Song K, Guo S, Gibson CJ, Ervin-Haynes A, Facon T. Long-term health-related quality of life in transplant-ineligible patients with newly diagnosed multiple myeloma receiving lenalidomide and dexamethasone. Leuk Lymphoma. 2018 Feb;59(2):398-405. doi: 10.1080/10428194.2017.1334125. Epub 2017 Jun 22.
Dumontet C, Hulin C, Dimopoulos MA, Belch A, Dispenzieri A, Ludwig H, Rodon P, Van Droogenbroeck J, Qiu L, Cavo M, Van de Velde A, Lahuerta JJ, Allangba O, Lee JH, Boyle E, Perrot A, Moreau P, Manier S, Attal M, Roussel M, Mohty M, Mary JY, Civet A, Costa B, Tinel A, Gaston-Mathé Y, Facon T. A predictive model for risk of early grade = 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial. Leukemia. 2018 Jun;32(6):1404-1413. doi: 10.1038/s41375-018-0133-x. Epub 2018 Apr 26.
Ailawadhi S, Jacobus S, Sexton R, Stewart AK, Dispenzieri A, Hussein MA, Zonder JA, Crowley J, Hoering A, Barlogie B, Orlowski RZ, Rajkumar SV. Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials. Blood Cancer J. 2018 Jul 6;8(7):67. doi: 10.1038/s41408-018-0102-7.
Jain T, Sonbol MB, Firwana B, Kolla KR, Almader-Douglas D, Palmer J, Fonseca R. High-Dose Chemotherapy with Early Autologous Stem Cell Transplantation Compared to Standard Dose Chemotherapy or Delayed Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant. 2019 Feb;25(2):239-247. doi: 10.1016/j.bbmt.2018.09.021. Epub 2018 Sep 20.
Facon T, Dimopoulos MA, Dispenzieri A, Catalano JV, Belch A, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis NJ, Banos A, Tiab M, Delforge M, Cavenagh JD, Geraldes C, Lee JJ, Chen C, Oriol A, De La Rubia J, White D, Binder D, Lu J, Anderson KC, Moreau P, Attal M, Perrot A, Arnulf B, Qiu L, Roussel M, Boyle E, Manier S, Mohty M, Avet-Loiseau H, Leleu X, Ervin-Haynes A, Chen G, Houck V, Benboubker L, Hulin C. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood. 2018 Jan 18;131(3):301-310. doi: 10.1182/blood-2017-07-795047. Epub 2017 Nov 17.
Ailawadhi S, DerSarkissian M, Duh MS, Lafeuille MH, Posner G, Ralston S, Zagadailov E, Ba-Mancini A, Rifkin R. Cost Offsets in the Treatment Journeys of Patients With Relapsed/Refractory Multiple Myeloma. Clin Ther. 2019 Mar;41(3):477-493.e7. doi: 10.1016/j.clinthera.2019.01.009. Epub 2019 Feb 14.
Pegourie B, Karlin L, Benboubker L, Orsini-Piocelle F, Tiab M, Auger-Quittet S, Rodon P, Royer B, Leleu X, Bareau B, Cliquennois M, Fuzibet JG, Voog E, Belhadj-Merzoug K, Decaux O, Rey P, Slama B, Leyronnas C, Zarnitsky C, Boyle E, Bosson JL, Pernod G; IFM Group. Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study. Am J Hematol. 2019 Jun;94(6):635-640. doi: 10.1002/ajh.25459. Epub 2019 Apr 1.
Public notes

Contacts
Principal investigator
Name 0 0
Christian Jacques, MD
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications