Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT00689936
- Lead Sponsor
- Celgene
- 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.
- Detailed Description
CC-5013-MM020/IFM 07-01 is a Phase III, multicenter, randomized, open-label, 3-arm study that will compare the efficacy and safety of two Lenalidomide plus low-dose dexamethasone regimens given for two different durations of time (i.e., until progressive disease \[PD\] or for up to a maximum of 18 four-week cycles) to that of MPT given for a maximum of 12 six-week cycles.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1623
-
Must understand and voluntarily sign informed consent form
-
Age ≥ 18 years at the time of signing consent
-
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
-
ECOG performance status of 0, 1, or 2
-
Able to adhere to the study visit schedule and other protocol requirements
-
Females of child-bearing potential (FCBP)^2:
- 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.
- 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.
-
Male Patients:
- 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.
- Must agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
- 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.
-
All patients must:
- Have an understanding that the study drug could have a potential teratogenic risk.
- Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
- 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.
-
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]).
-
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.
-
Pregnant or lactating females.
-
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)
-
Renal failure requiring hemodialysis or peritoneal dialysis.
-
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)
-
Patients who are unable or unwilling to undergo antithrombotic therapy.
-
Peripheral neuropathy of > grade 2 severity.
-
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lenalidomide / Dexamethasone for 18 cycles Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles Lenalidomide / Dexamethasone until disease progression Lenalidomide and low-dose dexamethasone Lenalidomide plus low-dose dexamethasone given until disease progression Melphalan, Prednisone, and Thalidomide (MPT) for 12 cycles Melphalan, Prednisone and Thalidomide Combination of Melphalan, Prednisone and Thalidomide given for 12 six-week cycles
- Primary Outcome Measures
Name Time Method Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC) 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. 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).
Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis 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 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).
- Secondary Outcome Measures
Name Time Method Kaplan Meier Estimates of Time to Treatment Failure (TTF) From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months. 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.
Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS) 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 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.
Percentage of Participants With an Objective Response Based on IRAC Review 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 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.
Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis 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 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.
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC 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 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.
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis 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 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.
Time to First Response Based on the Review by the IRAC 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 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.
Time to First Response Based on the Investigator Assessment at the Time of Final Analysis 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. 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.
Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months. 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.
Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT) From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months Time to second-line anti-myeloma therapy was defined as time from randomization to the start of another non-protocol anti-myeloma therapy.
Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months 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.
Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis 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 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.
Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review. 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 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.
Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review 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 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.
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review 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 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.
Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review 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 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.
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 Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation 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.
Change From Baseline in the EORTC QLQ-C30 Pain Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
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 Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Constipation Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
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 Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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).
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 Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
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 Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit 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.
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year Day 1 (randomization) up to last visit completed 25 July 2016 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.
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase 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 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.
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase 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 Renal function was assessed for participants from baseline to the most extreme value in creatinine clearance calculated using the Cockcroft-Gault estimation.
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase 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 Neutrophil counts was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase 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 Hemoglobin was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. 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 Improvement in platelets was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.
Improvement of Infection Rate by Observing the Historical Data Compared to the Clinical Data Base From randomization to 24 May 2013 Improvement of infection rate by observing historical data compared to the data within clinical database as not analyzed.
Trial Locations
- Locations (285)
Cedar Sinai Medical Center Dept of Medicine
🇺🇸Los Angeles, California, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Saint John Regional Hospital
🇨🇦Saint John, New Brunswick, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Hospital Leoben
🇦🇹Leoben, Austria
General Hospital Linz
🇦🇹Linz, Austria
Gold Coast Hospital
🇦🇺Southport, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Hospital of Barmherzige Schwestern Linz
🇦🇹Linz, Austria
Hospital of Elisabethinen Linz
🇦🇹Linz, Austria
Westmead Hospital
🇦🇺Wentworthville, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
Border Medical Oncology
🇦🇺Wodonga, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Australia
Hospital St. Polten
🇦🇹St. Pölten, Austria
Wollongong Hospital
🇦🇺Wollongong, Australia
London Health Science Centre
🇨🇦London, Ontario, Canada
Chu Estaing
🇫🇷Clermont Ferrand, France
MM-015.Wihelminenspital
🇦🇹Vienna, Austria
Hospital Wels
🇦🇹Wels, Austria
Hospital Wiener Neustadt
🇦🇹Wiener Neustadt, Austria
Les Cliniques du Sud Luxembourg
🇧🇪Arlon, Belgium
Jules Bordet Institut
🇧🇪Brussel, Belgium
University of Calgary
🇨🇦Calgary, Alberta, Canada
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Hospital of the Barmherzigen Bruder Vienna
🇦🇹Vienna, Austria
AZ St-Jan Brugge Oostende AV
🇧🇪Brugge, Belgium
Hopital Erasme
🇧🇪Brussels, Belgium
H. Hartziekenhuis Roeselare-Menen vzw campus Wilgenstraat
🇧🇪Roeselare, Belgium
Royal North Shore Hospital
🇦🇺St Leonards, Australia
Centre Hospitalier
🇫🇷Le Mans cedex, France
MM-015. Medizinische Universität Wien
🇦🇹Vienna, Austria
AZ-VUB
🇧🇪Brussels, Belgium
Virga Jesse Ziekenhuis
🇧🇪Hasselt, Belgium
Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
🇫🇷Bordeaux, France
Hopital Augustin Morvan
🇫🇷Brest cedex, France
CH
🇫🇷Le Chesnay Cedex, France
Centre Hospitalier William Morey
🇫🇷Chalon/Saone Cedex, France
Hopital dinstruction des armees Percy
🇫🇷Clamart Cedex, France
Centre Hospitalier Departemental
🇫🇷La Roche -Sur-Yon cedex 9, France
BC Cancer Agency - Fraser Valley Centre
🇨🇦Surrey, British Columbia, Canada
UZ Gent
🇧🇪Gent, Belgium
Chaoyang Hospital
🇨🇳Beijing, China
Centre Hospitalier de la cote basque
🇫🇷Bayonne, France
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
CH Rene Dubois
🇫🇷Cergy-Pontoise, France
CH Louis Pasteur
🇫🇷Colmar cedex, France
Centre Jean Bernard
🇫🇷Le Mans, France
Azienda Policlinico Umberto I, Universita La Sapienzadi Roma
🇮🇹Rome, Italy
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Clinique Claude BernardOncologie
🇫🇷Albi, France
CHRU Hopital du bocage
🇫🇷Dijon, France
CHRU-Hopital Claude Huriez
🇫🇷Lille cedex, France
CHU Sud
🇫🇷Amiens, France
CH Argenteuil Victor Dupouy
🇫🇷Argenteuil, France
Hopital Avicenne
🇫🇷Bobigny Cedex, France
Hopital Antoine Beclere
🇫🇷Clamart, France
Hopital Henri Mondor
🇫🇷Creteil, France
Institut Prive de Cancerologie
🇫🇷Grenoble, France
Universitatsklinikum Essen-
🇩🇪Essen, Germany
Theagenio Anticancer Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Alexandra Hospital, University of Athens
🇬🇷Athens, Greece
Adelaide and Meath Hospital
🇮🇪Dublin, Ireland
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Clinica Ematologica, A.O.U. San Martino di Genova
🇮🇹Genova, Italy
Policlinico di Modena
🇮🇹Modena, Italy
CHRU Hopital sud Medecine Interne
🇫🇷Rennes cedex 02, France
Centre Henri Becquerel
🇫🇷Rouen cedex, France
Chungnam National University Hospital
🇰🇷Daejon, Korea, Republic of
Medizinische Klinik - Abteilung II
🇩🇪Tübingen, Germany
Casa di Cura La Maddalena, Divisione di Ematologia
🇮🇹Palermo, Italy
Ospedale Civile
🇮🇹Piacenza, Italy
A.O. Universitaria Ospedale S.Chiara Dip.Oncologia, Div. Ematologia
🇮🇹Pisa, Italy
Hopital R. Debre
🇫🇷Reims cedex, France
Institut de Cancerologie de Loire
🇫🇷St Priest en Jarez, France
Evangelismos Hospital of Athens
🇬🇷Athens, Greece
Dept of Haematology St Bartholomews Hospital
🇬🇧London, United Kingdom
Oncologia Medica, Università della Magna Grecia
🇮🇹Catanzaro, Italy
Royal Bournemouth Hosp
🇬🇧Bournemouth Dorset, United Kingdom
Medizinische Kinik und Poliklinik I
🇩🇪Dresden, Germany
Klinik fur Innere Medizin III
🇩🇪Ulm, Germany
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University of Athens
🇬🇷Athens, Greece
Mater Misercordiae Hospital
🇮🇪Dublin, Ireland
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Karolinska University HospitalSolna
🇸🇪Stockholm, Sweden
St. Görans Hospital
🇸🇪Stockholm, Sweden
Gwynedd Hospital
🇬🇧Bangor, United Kingdom
Royal United Hospital
🇬🇧Bath, United Kingdom
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust
🇬🇧Sheffield, United Kingdom
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Hosptial La Fe
🇪🇸Valencia, Spain
Abteilung Onkologie Haematologie des Kantonsspitals Aarau
🇨🇭Aarau, Switzerland
UniversitatsSpital Basel
🇨🇭Basel, Switzerland
Belfast City Hospital Haematology Department
🇬🇧Belfast Northern Ireland, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Centre Hospitalier Universitaire Vaudois CHUV
🇨🇭Lausanne, Switzerland
Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Royal Free Hospital
🇬🇧London, United Kingdom
Pinderfields General Hospital
🇬🇧West Yorkshire, United Kingdom
Birminghman QE
🇬🇧Birmingham West Midlands, United Kingdom
University Hospital of Wales - Cardiff
🇬🇧Cardiff, United Kingdom
The Beatson West of Scotland Centre
🇬🇧Glasgow, United Kingdom
Kantonsspital Munsterlingen
🇨🇭Münsterlingen (TG), Switzerland
China Medical University Hospital
🇨🇳Taichung City, Taiwan
New Cross Hospital- Wolverhampton
🇬🇧Wolverhampton, United Kingdom
Peking University People's Hospital
🇨🇳Beijing, China
West China Hospital of Sichuan University
🇨🇳Chengdu, China
Ruijin Hospital Shanghai Jiaotong University
🇨🇳Shanghai, China
Blood Disease Hospital, Chinese Academy of Medical Science and Peking Union Medical College
🇨🇳Tianjin, China
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
Attiko Hospital of Athens
🇬🇷Athens, Greece
Metaxa Hospital Peiraias
🇬🇷Piraeus, Greece
Royal Columbian Hospital
🇨🇦New Westminster, British Columbia, Canada
Cliniques Universitaires UCL de Mont-Godine
🇧🇪Yvoir, Belgium
Western Hospital
🇦🇺Footscray, Victoria, Australia
University Hospital Galway
🇮🇪Galway, Ireland
Hospitais da Universidade de Coimbra
🇵🇹Coimbra, Portugal
Instituto Portugues de Oncologia de Lisboa
🇵🇹Lisboa, Portugal
Inselsspital Bern
🇨🇭Berne, Switzerland
British Columbia Cancer Agency
🇨🇦Kelowna, British Columbia, Canada
National Taiwan University Hospital
🇨🇳Tapei, Taiwan
Leukemia/BMT Program of BCDiv of Hem, Vancouver Gen Hosp
🇨🇦Vancouver, British Columbia, Canada
Hospital de Sao Marcos
🇵🇹Braga, Portugal
Veteran General Hospital - Taipei
🇨🇳Taipei, Taiwan
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Kantonsspital Graubunden
🇨🇭Chur, Switzerland
University of AL Birmingham
🇺🇸Birmingham, Alabama, United States
University of California, San Francisco- California
🇺🇸San Francisco, California, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Policlinico S. Orsola
🇮🇹Bologna, Italy
Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce
🇮🇹Lecce, Italy
U.O. di Ematologia e Trapianto di Midollo Osseo
🇮🇹Milano, Italy
Istituto Europeo di Oncologia - IEO
🇮🇹Milano, Italy
Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Policlinico San Matteo Universita Di Pavia
🇮🇹Pavia 2, Italy
Linkoping University Hospital
🇸🇪Linkoping, Sweden
Hospital Maisonneuve - Rosemont
🇨🇦Montreal, Quebec, Canada
McGill University
🇨🇦Montreal, Quebec, Canada
Sir Mortimer B. Davis - Jewish Genl
🇨🇦Montreal, Quebec, Canada
Derriford Hospital
🇬🇧Plymouth Crownhill Devon, United Kingdom
Hopital de Fleyriat
🇫🇷Bourg en Bresse cedex, France
Centre Francois Baclesse
🇫🇷Caen cedex 5, France
Centre Hospitalier General
🇫🇷Dunkerque, France
CHRU
🇫🇷Grenoble cedex 09, France
Kremlin Bicetre
🇫🇷Le Kremlin bicetre CDX, France
GH de Institut Catholique St Vincent
🇫🇷Lille, France
CH - Hôpital Dupuytren
🇫🇷Limoges Cedex 1, France
CHU Hopital Edouard Herriot
🇫🇷Lyon cedex, France
Centre Hospitalier de Valence
🇫🇷Lyon, France
Institut Paoli-Calmettes
🇫🇷Marseille Cedex 9, France
Hopital de Mercy
🇫🇷METZ cedex 3, France
Hopital Emile Muller
🇫🇷Mulhouse, France
CHRU - Hotel Dieu
🇫🇷Nantes, France
CH La Source
🇫🇷Orleans, France
Hopital Necker
🇫🇷Paris, France
CHU Reims - Hôpital Maison Blanche
🇫🇷Reims, France
CHRU Hôpital de Pontchaillou
🇫🇷Rennes Cedex, France
Centre Hospitalier Yves Le Foll
🇫🇷St-Brieuc cedex 1, France
CHRU Hopital Bretonneau
🇫🇷Tours cedex, France
CH P. Chubert
🇫🇷Vannes cedex, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Severance Hospital
🇰🇷Seongsanno, Korea, Republic of
Integrated Community Oncology Network
🇺🇸Orange Park, Florida, United States
Gainesville Heme Oncology Associates
🇺🇸Gainesville, Florida, United States
Stanford University Stanford
🇺🇸Stanford, California, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
Gulf Coast Oncology
🇺🇸Saint Petersburg, Florida, United States
Southern Illinois Hematology Oncology
🇺🇸Centralia, Illinois, United States
Palm Beach Cancer Institute, LLC
🇺🇸West Palm Beach, Florida, United States
John H Stroger Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Orchard Healthcare Research, Inc.
🇺🇸Chicago, Illinois, United States
Ingalls Cancer Institute
🇺🇸Harvey, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Dakota Cancer Institute
🇺🇸Fargo, North Dakota, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Maine Center for Cancer Medicine Blood Disorders
🇺🇸Scarborough, Maine, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Kaiser Permanente Northwest Oncology Hematology
🇺🇸Portland, Oregon, United States
St. Luke's Hospital and Health Network
🇺🇸Allentown, Pennsylvania, United States
The Cancer Center
🇺🇸Collierville, Tennessee, United States
University of Tennessee Cancer Institute
🇺🇸Memphis, Tennessee, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology
🇦🇺E. Melbourne, Victoria, Australia
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Geelong Hospital
🇦🇺Geelong, Australia
Cabrini Hospital
🇦🇺Malvern, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Australia
MM-015. Salzburger Landkliniken, St. Johanns-Spital, Universitätsklinik fur Innere Medizin III
🇦🇹Salzburg, Austria
ZNA Stuivenberg Centrumziekenhuis
🇧🇪Antwerpen, Belgium
Vancouver Island Cancer Center
🇨🇦Victoria, British Columbia, Canada
Queen Elizabeth II Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Hospital Charles LeMoyne
🇨🇦Greenfield Park, Quebec, Canada
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hopital du Sacre-Coeur de Montreal
🇨🇦Montreal, Quebec, Canada
Hopital de la Cite-de-la-Sante
🇨🇦Laval, Quebec, Canada
Hotel-Dieu de Levis
🇨🇦Levis, Quebec, Canada
CHUM- Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
CHUQ - Hotel-Dieu de QuebecHematology - Oncology
🇨🇦Quebec, Canada
CHU
🇫🇷Caen, France
CHG Rodez
🇫🇷Rodez, France
Hopital J MonodRhumato Nord
🇫🇷Le Havre, France
Centre Leon Berard
🇫🇷Lyon, France
CHU Montpellier - Hôpital Lapeyronie
🇫🇷Montpellier Cedex 5, France
Clinique Pont de chaume Oncologie et Radiotherapie
🇫🇷Montauban cedex, France
Hopital de lArchet 1
🇫🇷Nice cedex 3, France
Centre Antoine Lacassagne Oncologie medicale et Hematologie
🇫🇷Nice cedex 1, France
CU CHU Clemenceau
🇫🇷Poitiers cedex, France
Hopital Cochin
🇫🇷Paris Cedex 14, France
Hopital Saint Louis
🇫🇷Paris, France
CHU Hôpital St-Antoine
🇫🇷Paris, France
CHRU - Hopital du Haut Leveque
🇫🇷Pessac, France
Centre Rene Huguenin
🇫🇷Saint Cloud, France
CHRU Hôpital de Hautepierre
🇫🇷Strasbourg, France
CHRU Hopital Purpan
🇫🇷Toulouse cedex 9, France
CHRU Hopital Trousseau
🇫🇷Tours, France
CHRU Hôpitaux de Brabois
🇫🇷Vandoeuvre Cedex, France
Universitaetsklinikum Dusseldorf Klinik fuer Haematologie
🇩🇪Dusseldorf, Germany
Staedtische Kliniken Frankfurt am Main Hochst
🇩🇪Frankfurt am Main, Germany
Universitatsklinikum Giessen
🇩🇪Giessen, Germany
Ernst-Moritz-Arndt-Universität Greifswald
🇩🇪Greifswald, Germany
Universitatsklinikum Jena
🇩🇪Jena, Germany
Askepios Klinik St. Georg
🇩🇪Hamburg, Germany
Medizinische Klinik und Poliklinik II
🇩🇪Leipzig, Germany
Universitatsklinikum schleswig-Holstein
🇩🇪Lübeck, Germany
Poliklinik A
🇩🇪Muenster, Germany
Klinikum der Johann-Wolfgang-Goethe-Universtat
🇩🇪München, Germany
Medizinische Klinik III Klinikum der Universität München-Großhadern
🇩🇪München, Germany
Medizinische Fakultat der Universitat Rostock
🇩🇪Rostock, Germany
Zentrum F. Innere Medizin II Robert- Bosch-Krankenhaus GmBH
🇩🇪Stuttgart, Germany
Unità Operativa di Oncoematologia, Ospedale di Matera
🇮🇹Matera, Italy
Presidio Ospedaliero A. Perrino
🇮🇹Milano, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Istituto Nazionale Tumori Regina Elena, Struttura Complessa Ematologia ed Unita di Cellule Staminali
🇮🇹Roma, Italy
Ospedale Molinette
🇮🇹Torino, Italy
Hallym University Sacred Heart Hospital
🇰🇷Anyang, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Daegu Catholic University Medical Center 3056-6
🇰🇷Daegu, Korea, Republic of
Hwasun Chonnam National University Hospital
🇰🇷Hwasun-goon, Korea, Republic of
Chonbuk National University Hospital 42
🇰🇷Jeonju, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Auckland City Hospital
🇳🇿Auckland, New Zealand
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul - Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Wellington Hospital
🇳🇿Newtown, New Zealand
Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Instituto Português de Oncologia Porto
🇵🇹Porto, Portugal
Hospital de Santo Antonio- Porto
🇵🇹Porto, Portugal
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona (Barcelona), Spain
Instituto Catalan de Oncologia-Hospital Duran
🇪🇸Barcelona, Spain
Hospital Reina Sofia
🇪🇸Cordoba, Spain
Hospital Univ. Josep Trueta
🇪🇸Girona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital General Universitario Morales Messeguer
🇪🇸Murcia, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Spain
Hospital Clinico Virgen de la Victoria
🇪🇸Málaga, Spain
Clinica Universitaria de Navarra,
🇪🇸Pamplona, Spain
Hospital Universtario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital de Donosti
🇪🇸San Sebastian, Spain
Hospital Sant Pau
🇪🇸Reus, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Karolinska University Hospital Huddinge
🇸🇪Stockholm, Sweden
Churchhill Hospital
🇬🇧Oxford, United Kingdom
Guy's and St Thomas' Hospital - London
🇬🇧London, United Kingdom
Gosford Hospital
🇦🇺Gosford, Australia
Hospital Clinico Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Arena Oncology Associates, PC
🇺🇸Lake Success, New York, United States