Multiple Myeloma
Conditions
Keywords
Lenalidomide, dexamethasone, newly diagnosed multiple myeloma
Brief summary
To determine the efficacy of lenalidomide in combination with low-dose dexamethasone in Japanese subjects with previously untreated multiple myeloma.
Interventions
DRUGLenalidomide
25 mg oral lenalidomide once daily on Days 1-21 of each 28-day cycle
DRUGdexamethasone
40 mg oral dexamethasone once daily on Days 1, 8, 15 and 22 of each 28-day cycle
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 20 years at the time of signing the informed consent document * Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted * Able to adhere to the study visit schedule and other protocol requirements * Previously untreated, symptomatic multiple myeloma * Have measurable disease by protein electrophoresis analyses * At least 65 years of age or older or, if younger than 65 years of age, not candidates for hematopoietic stem cell transplantation * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Must agree to comply to Lenalidomide Pregnancy Prevention Risk Management Plan
Exclusion criteria
* Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study * Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study * Any condition that confounds the ability to interpret data from the study * Previous treatment with anti-myeloma therapy * Pregnant or lactating females * Any of the following laboratory abnormalities: * Absolute neutrophil count (ANC) \< 1,000/microL (1.0 × 10\^9/L ) * Untransfused platelet count (a platelet count drawn at least 7 days after the administration of the last platelet transfusion) \< 50,000 cells/microL (50 × 10\^9/L) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3.0 × upper limit of normal * Renal failure requiring hemodialysis or peritoneal dialysis * Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years * Subjects who are unable or unwilling to undergo antithrombotic therapy. * Peripheral neuropathy of ≥ grade 2 severity. * Uncontrolled systemic fungal, bacterial, or viral infection * Known human immunodeficiency virus (HIV) positivity (subjects who are receiving antiretroviral therapy for HIV disease) * Hepatitis Bs (HBs) antigen-positive, or hepatitis C virus (HCV) antibody-positive. In case HBc antibody and/or HBs antibody is positive even if HBs antigen-negative, a Hepatitis B virus (HBV) DNA test should be performed and if positive the subject will be excluded. * Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis. * Ineligible for dexamethasone or dexamethasone is contraindicated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | From first dose until the data cut-off date of 15 July 2014. Median time on follow-up was 61.6 weeks. | Number of Complete Responses (CR) plus Very Good Partial Response (VGPR) plus Partial Response (PR) based on the International Myeloma Working Group criteria (IMWG). Any participant who achieved a CR, VGPR, or PR while on study treatment was defined as a responder. CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: 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; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up time was 61.6 weeks. | Time to response was calculated for the responders as the time from the first dose date to the initial documented response (CR, VGPR or PR). CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: 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; PR: ≥ 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 is also required. |
| Duration of Response | From the first dose of study drug treatment until the data cut-off date of 15 July2014. Median follow up time was 61.6 weeks. | Duration of response was calculated for the responders as the time from the initial documented response (CR or VGPR or PR) to the first documented progression or death due to any cause, whichever occurred first. Duration of response for participants last known to be alive with no progression after a CR, VGPR, or PR were censored at the date of last adequate response assessment. |
| Progression Free Survival (PFS) | From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up for PFS assessments was 61.6 weeks. | PFS was calculated as the time from the first dose date to the first documented progression based on IWG criteria or death due to any cause, whichever occurred first. If progression or death was not documented at the time of data cutoff date, these observations were censored at the last adequate assessment date showing evidence of no progression or death. |
| Overall Survival (OS) | From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow up is 14.2 months | The time from the start of study treatment to death due to any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. |
| Number of Participants With Adverse Events | From first dose of study drug treatment through to 28 days after the last dose, until the data cut-off date of 15 July 2014; median treatment duration was 60 weeks | An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. 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. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death. |
Countries
Japan
Participant flow
Pre-assignment details
This is an ongoing open-label, single arm, 5 year study consisting of a 28-day screening period followed by a treatment period where participants receive lenalidomide and dexamethasone until their disease progresses or the lenalidomide is discontinued for any reason. This report includes data up to the cut-off of 15 July 2014.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide Plus Dexamethasone Lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease or lenalidomide discontinuation for any reason.
Dexamethasone 40 mg orally once daily on Days 1, 8, 15 and 22 in each 28-day cycle until progressive disease or lenalidomide discontinuation for any reason. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow Up Phase | Death | 4 |
| Follow Up Phase | Withdrawal by Subject | 1 |
| Treatment Phase | Adverse Event | 4 |
| Treatment Phase | Disease progression | 1 |
| Treatment Phase | Other | 4 |
| Treatment Phase | Protocol Violation | 1 |
| Treatment Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Lenalidomide Plus Dexamethasone |
|---|---|
| Age, Continuous | 74.2 years STANDARD_DEVIATION 7.01 |
| Age, Customized ≤ 75 Years Old | 14 participants |
| Age, Customized > 75 Years Old | 12 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active | 13 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1= Restrictive but Ambulatory | 7 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but Unable to Work | 6 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self-Care | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4 = Completely Disabled | 0 participants |
| Multiple Myeloma Stage before Study Entry Stage I | 7 participants |
| Multiple Myeloma Stage before Study Entry Stage II | 14 participants |
| Multiple Myeloma Stage before Study Entry Stage III | 5 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 11 / 26 |
Outcome results
Primary
Overall Response Rate
Number of Complete Responses (CR) plus Very Good Partial Response (VGPR) plus Partial Response (PR) based on the International Myeloma Working Group criteria (IMWG). Any participant who achieved a CR, VGPR, or PR while on study treatment was defined as a responder. CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: 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; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: From first dose until the data cut-off date of 15 July 2014. Median time on follow-up was 61.6 weeks.
Population: Efficacy Evaluable (EE) Population consists of all participants who met the protocol requirements (all eligibility criteria) and were evaluated after receiving at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Overall Response Rate | 87.5 percentage of participants |
p-value: <0.000195% CI: [74.269, 100]Binomial test for dichotomized response
Secondary
Duration of Response
Duration of response was calculated for the responders as the time from the initial documented response (CR or VGPR or PR) to the first documented progression or death due to any cause, whichever occurred first. Duration of response for participants last known to be alive with no progression after a CR, VGPR, or PR were censored at the date of last adequate response assessment.
Time frame: From the first dose of study drug treatment until the data cut-off date of 15 July2014. Median follow up time was 61.6 weeks.
Population: Efficacy Evaluable (EE) Population consists of all participants who meet protocol requirements (all eligibility criteria) and were evaluated after receiving at least one dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Duration of Response | NA months |
Secondary
Number of Participants With Adverse Events
An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. 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. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.
Time frame: From first dose of study drug treatment through to 28 days after the last dose, until the data cut-off date of 15 July 2014; median treatment duration was 60 weeks
Population: Safety population includes all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Any adverse event | 26 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | TEAE related to study drug | 25 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | TEAE related to Lenalidomide | 25 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | TEAE related to Dexamethasone | 20 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Grade 3-4 adverse event | 18 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Grade 3-4 adverse event related to any study drug | 15 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Grade 3-4 adverse event related to Lenalidomide | 15 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Grade 3-4 adverse event related to Dexamethasone | 4 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Serious TEAE | 11 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Serious TEAE related to any study drug | 8 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Serious TEAE related to Lenalidomide | 8 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Serious TEAE related to Dexamethasone | 3 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | TEAE leading to discontinuation of either drug | 4 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | TEAE leading to discontinuation of lenalidomide | 4 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | TEAE leading to discontinuation of dexamethasone | 2 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Related TEAE discontinuation of either drug | 4 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Related TEAE discontinuation of lenalidomide | 4 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events | Related TEAE discontinuation of dexamethasone | 0 participants |
Secondary
Overall Survival (OS)
The time from the start of study treatment to death due to any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Time frame: From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow up is 14.2 months
Population: Efficacy Evaluable (EE) Population consists of all participants who met the protocol requirements (all eligibility criteria) and were evaluated after receiving at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Overall Survival (OS) | 17.71 months |
Secondary
Progression Free Survival (PFS)
PFS was calculated as the time from the first dose date to the first documented progression based on IWG criteria or death due to any cause, whichever occurred first. If progression or death was not documented at the time of data cutoff date, these observations were censored at the last adequate assessment date showing evidence of no progression or death.
Time frame: From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up for PFS assessments was 61.6 weeks.
Population: Efficacy Evaluable (EE) Population consists of all participants who met the protocol requirements (all eligibility criteria) and were evaluated after receiving at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Progression Free Survival (PFS) | NA months |
Secondary
Time to Response
Time to response was calculated for the responders as the time from the first dose date to the initial documented response (CR, VGPR or PR). CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: 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; PR: ≥ 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 is also required.
Time frame: From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up time was 61.6 weeks.
Population: Efficacy Evaluable (EE) Population consists of all participants who meet protocol requirements (all eligibility criteria) and were evaluated after receiving at least one dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Time to Response | 1.97 months |