Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Celgene, Revlimid, CC-5013
Brief summary
To compare the efficacy of oral CC-5013 in combination with oral pulse high-dose dexamethasone to that of placebo and oral high-dose pulse dexamethasone as treatment for subjects with relapsed or refractory multiple myeloma.
Interventions
DRUGCC-5013 plus dexamethasone
25 mg daily for 21 days every 28 days.
DRUGDexamethasone plus Placebo
Oral pulse dexamethasone is administered at a dose of 40mg daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4. Beginning with Cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg daily for Days 1-4 every 28 days. In addition, oral placebo capsules will be administered for 28 days of every cycle.
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prior or current diagnosis Durie-Salmon stage II or III multiple myeloma. * Measurable levels of myeloma paraprotein in serum or urine (24-hour collection sample). * Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2 * Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days of starting study drug
Exclusion criteria
* Prior development of disease progression during high-dose dexamethasone containing therapy * Pregnant or lactating females * The development of a desquamating rash while taking thalidomide * Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment * Laboratory abnormalities: Absolute neutrophil count less than 1,000 cells/mm3 * Laboratory abnormalities: Platelet count \< 75,000/mm3 * Laboratory abnormalities: Serum creatinine \> 2.5 mg/dL * Laboratory abnormalities: Serum Serum glutamic oxaloacetic transaminase (SGOT)/Aspartate aminotransferase (AST) or Serum glutamic pyruvic transaminase (SGPT)/Alanine aminotransferase (ALT) \> 3.0 x upper limit of normal * Laboratory abnormalities: Serum total bilirubin \> 2.0 mg/dL * Prior history of malignancies other than multiple myeloma unless the subject has been free of the disease for ≥ 3 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Time to Tumor Progression (TTP) | From randomization up to cut-off date of 03 August 2005; up to 24 months | Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia. |
| Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008) | From randomization up to cut-off date of 02 March 2008; up to 51 months | Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Myeloma Response Rates Based on Best Response Assessment | Randomization to 03 August 2005; up to 24 months | Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma. |
| Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Randomization to data cut-off of 02 Mar 2008; up to 51 months | Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma. |
| Number of Participants With Adverse Events (AE) | From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 25 June 2013; up to 90 months | An AE is any sign, symptom, illness, or diagnosis that appears or worsens during the course of the study. Treatment-emergent AEs (TEAEs) are any AE occurring or worsening on or after the first treatment of the study drug and within 30 days after the last cycle end date of study drug. A serious AE = any AE which results in death; is life-threatening; requires or prolongs existing inpatient hospitalization; results in persistent or significant disability is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE, Version 2.0): 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. |
| Kaplan-Meier Estimate of Overall Survival (OS) | Randomization to data cut off of 03 August 2005; up to 24 months | OS was calculated as the time from randomization to death from 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 to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale | Randomization to cut off date of 03 August 2005; up to 24 months | The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented. |
| Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) | Randomization to cut off date of 02 March 2008; up to 51 months | The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented. |
| Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone) | Up to unblinding data cut off of 03 August 2005; up to 24 months | Time from randomization to the date of the first occurrence of a symptomatic SRE (clinical need for radiotherapy or surgery to bone). |
| Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008) | Randomization to data cut off of 02 March 2008; up to 51 months | OS was calculated as the time from randomization to death from 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. |
Countries
Australia, Austria, Belgium, France, Germany, Greece, Ireland, Israel, Italy, Poland, Spain, Sweden, Switzerland, Ukraine, United Kingdom
Participant flow
Recruitment details
The study was conducted at 55 sites in Australia, Europe, and Israel. Eligible participants were randomized in a 1:1 ratio to: lenalidomide plus oral pulse high-dose dexamethasone or Placebo plus oral pulse high-dose dexamethasone.
Pre-assignment details
A pre-specified interim analysis revealed a highly significant benefit favoring the lenalidomide/dexamethasone regimen, crossing the pre-specified O'Brien-Fleming superiority boundary. A decision was made to unblind the study allowing those receiving Placebo/dexamethasone to receive the lenalidomide/dexamethasone regimen.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide Plus Dexamethasone Lenalidomide 25 mg by mouth (PO) daily (QD) on Days 1 to 21 and a matching placebo capsule QD on Days 22 to 28 of each 28-day cycle.
Dexamethasone 40mg PO QD on Days 1-4, 9-12, and 17-20 of each 28 day cycle for cycles 1 through 4. Beginning with Cycle 5, dexamethasone dosing schedule was reduced to 40mg PO QD on Days 1 to 4 every 28 days for the remaining cycles. | 176 |
| Placebo Plus Dexamethasone Placebo PO daily on Days 1 to 28 of each 28 day cycle.
Dexamethasone 40mg PO QD on Days 1-4, 9-12, and 17-20 of each 28-day cycle for Cycles 1 through 4. Beginning with Cycle 5, dexamethasone dosing schedule was reduced to 40mg PO QD for Days 1-4 every 28 days. | 175 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Treatment (Up to 03 Aug 2005) | Adverse Event | 18 | 12 |
| Blinded Treatment (Up to 03 Aug 2005) | Death | 11 | 10 |
| Blinded Treatment (Up to 03 Aug 2005) | Lack of therapeutic effect | 1 | 3 |
| Blinded Treatment (Up to 03 Aug 2005) | Other | 2 | 1 |
| Blinded Treatment (Up to 03 Aug 2005) | Progression of disease | 67 | 122 |
| Blinded Treatment (Up to 03 Aug 2005) | Withdrawal by Subject | 23 | 8 |
| Long Term Extension (Up to 25 Jun 2013) | Adverse Event | 1 | 0 |
| Long Term Extension (Up to 25 Jun 2013) | Death | 0 | 1 |
| Long Term Extension (Up to 25 Jun 2013) | Other | 12 | 4 |
| Long Term Extension (Up to 25 Jun 2013) | Progression of Disease | 7 | 3 |
| Long Term Extension (Up to 25 Jun 2013) | Withdrawal by Subject | 1 | 0 |
| On Study at Time of Unblinding | Adverse Event | 22 | 12 |
| On Study at Time of Unblinding | Death | 11 | 11 |
| On Study at Time of Unblinding | Lack of Efficacy | 1 | 3 |
| On Study at Time of Unblinding | Other | 5 | 4 |
| On Study at Time of Unblinding | Progression of disease | 92 | 128 |
| On Study at Time of Unblinding | Withdrawal by Subject | 24 | 9 |
Baseline characteristics
| Characteristic | Total | Lenalidomide Plus Dexamethasone | Placebo Plus Dexamethasone |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.47 | 62.2 years STANDARD_DEVIATION 10.12 | 62.9 years STANDARD_DEVIATION 8.8 |
| Baseline multiple myeloma stage Stage I | 19 participants | 11 participants | 8 participants |
| Baseline multiple myeloma stage Stage II | 107 participants | 50 participants | 57 participants |
| Baseline multiple myeloma stage Stage III | 225 participants | 115 participants | 110 participants |
| Eastern Cooperative Oncology Group Performance Status 0 = (Fully Active) | 143 participants | 78 participants | 65 participants |
| Eastern Cooperative Oncology Group Performance Status 1 = (Restrictive but Ambulatory) | 151 participants | 72 participants | 79 participants |
| Eastern Cooperative Oncology Group Performance Status 2 = Ambulatory unable to Work) | 50 participants | 23 participants | 27 participants |
| Eastern Cooperative Oncology Group Performance Status 3 = (Limited Self-Care) | 1 participants | 0 participants | 1 participants |
| Eastern Cooperative Oncology Group Performance Status 4 = (Completely Disabled) | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group Performance Status Missing | 6 participants | 3 participants | 3 participants |
| Number of Prior Anti-Myeloma Therapies 1 Prior anti-myeloma therapy | 113 participants | 56 participants | 57 participants |
| Number of Prior Anti-Myeloma Therapies 2 or more prior anti-myeloma therapies | 238 participants | 120 participants | 118 participants |
| Sex: Female, Male Female | 144 Participants | 72 Participants | 72 Participants |
| Sex: Female, Male Male | 207 Participants | 104 Participants | 103 Participants |
| Time from First Pathological Diagnosis | 3.7 years | 3.4 years | 4.0 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 175 / 176 | 173 / 175 |
| serious Total, serious adverse events | 105 / 176 | 79 / 175 |
Outcome results
Primary
Kaplan-Meier Estimate of Time to Tumor Progression (TTP)
Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time frame: From randomization up to cut-off date of 03 August 2005; up to 24 months
Population: Intent to treat included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Kaplan-Meier Estimate of Time to Tumor Progression (TTP) | 52.1 weeks |
| Placebo Plus Dexamethasone | Kaplan-Meier Estimate of Time to Tumor Progression (TTP) | 20.1 weeks |
p-value: <0.00195% CI: [0.24, 0.438]Log Rank
Primary
Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008)
Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time frame: From randomization up to cut-off date of 02 March 2008; up to 51 months
Population: Intent to treat included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008) | 52.4 weeks |
| Placebo Plus Dexamethasone | Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008) | 20.1 weeks |
p-value: <0.00195% CI: [0.27, 0.478]Log Rank
Secondary
Kaplan-Meier Estimate of Overall Survival (OS)
OS was calculated as the time from randomization to death from 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: Randomization to data cut off of 03 August 2005; up to 24 months
Population: Intent to Treat population includes all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Kaplan-Meier Estimate of Overall Survival (OS) | NA weeks |
| Placebo Plus Dexamethasone | Kaplan-Meier Estimate of Overall Survival (OS) | NA weeks |
p-value: 0.10595% CI: [0.498, 1.07]Log Rank
Secondary
Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008)
OS was calculated as the time from randomization to death from 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: Randomization to data cut off of 02 March 2008; up to 51 months
Population: Intent to Treat population includes all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008) | 161.9 weeks |
| Placebo Plus Dexamethasone | Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008) | 133.3 weeks |
p-value: 0.30295% CI: [0.651, 1.143]Log Rank
Secondary
Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008)
Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma.
Time frame: Randomization to data cut-off of 02 Mar 2008; up to 51 months
Population: Intent to Treat Population includes all participants who were randomized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Partial Response (PR) | 42.6 percentage of participants |
| Lenalidomide Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Progressive Disease (PD) | 3.4 percentage of participants |
| Lenalidomide Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Stable Disease (SD) | 28.4 percentage of participants |
| Lenalidomide Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Not Evaluable (NE) those without response data | 8.5 percentage of participants |
| Lenalidomide Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Complete Response (CR) | 17.0 percentage of participants |
| Placebo Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Not Evaluable (NE) those without response data | 5.7 percentage of participants |
| Placebo Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Complete Response (CR) | 4.0 percentage of participants |
| Placebo Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Partial Response (PR) | 19.4 percentage of participants |
| Placebo Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Stable Disease (SD) | 56.6 percentage of participants |
| Placebo Plus Dexamethasone | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) | Progressive Disease (PD) | 14.3 percentage of participants |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Adverse Events (AE)
An AE is any sign, symptom, illness, or diagnosis that appears or worsens during the course of the study. Treatment-emergent AEs (TEAEs) are any AE occurring or worsening on or after the first treatment of the study drug and within 30 days after the last cycle end date of study drug. A serious AE = any AE which results in death; is life-threatening; requires or prolongs existing inpatient hospitalization; results in persistent or significant disability is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE, Version 2.0): 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 through to 30 days after the last dose, until the data cut-off date of 25 June 2013; up to 90 months
Population: The safety population includes all participants who received at least one dose of study drug regimen
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Adverse Event | 176 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥Death within ≤ 30 days of last dose of study drug | 17 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 AE leading to study drug discontinuation | 46 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 1 or Higher Adverse Event | 176 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 AE leading to dose reduction or interruption | 137 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 2 or Higher Adverse Event | 168 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Drug-Related Adverse Event | 160 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 3 or Higher Adverse Event | 146 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Serious Adverse Event | 105 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 4 or Higher Adverse Event | 52 participants |
| Lenalidomide Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Drug-Related Serious Adverse Event | 54 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 4 or Higher Adverse Event | 37 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Adverse Event | 175 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Serious Adverse Event | 79 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 AE leading to dose reduction or interruption | 100 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Drug-Related Adverse Event | 151 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Drug-Related Serious Adverse Event | 30 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥Death within ≤ 30 days of last dose of study drug | 20 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 1 or Higher Adverse Event | 175 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 2 or Higher Adverse Event | 167 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 Grade 3 or Higher Adverse Event | 119 participants |
| Placebo Plus Dexamethasone | Number of Participants With Adverse Events (AE) | ≥ 1 AE leading to study drug discontinuation | 31 participants |
Secondary
Summary of Myeloma Response Rates Based on Best Response Assessment
Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma.
Time frame: Randomization to 03 August 2005; up to 24 months
Population: Intent to Treat Population includes all participants who were randomized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Partial Response (PR) | 43.8 percentage of participants |
| Lenalidomide Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Progressive Disease (PD) | 2.8 percentage of participants |
| Lenalidomide Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Stable Disease (SD) | 29.0 percentage of participants |
| Lenalidomide Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Not Evaluable (NE) those without response data | 9.1 percentage of participants |
| Lenalidomide Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Complete Response (CR) | 15.3 percentage of participants |
| Placebo Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Not Evaluable (NE) those without response data | 5.7 percentage of participants |
| Placebo Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Complete Response (CR) | 4.0 percentage of participants |
| Placebo Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Partial Response (PR) | 19.4 percentage of participants |
| Placebo Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Stable Disease (SD) | 56.6 percentage of participants |
| Placebo Plus Dexamethasone | Summary of Myeloma Response Rates Based on Best Response Assessment | Progressive Disease (PD) | 14.3 percentage of participants |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone)
Time from randomization to the date of the first occurrence of a symptomatic SRE (clinical need for radiotherapy or surgery to bone).
Time frame: Up to unblinding data cut off of 03 August 2005; up to 24 months
Population: Analysis not performed due to an insufficient number of participants with SRE
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone) | NA participants |
| Placebo Plus Dexamethasone | Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone) | NA participants |
Secondary
Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented.
Time frame: Randomization to cut off date of 03 August 2005; up to 24 months
Population: Intent to Treat includes all participants who were randomized to study drug; a total of six ECOG scores were missing at the time of the Aug 2005 cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale | 10.1 weeks |
| Placebo Plus Dexamethasone | Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale | 12.3 weeks |
p-value: 0.27195% CI: [0.887, 1.532]Log Rank
Secondary
Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008)
The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented.
Time frame: Randomization to cut off date of 02 March 2008; up to 51 months
Population: Intent to Treat includes all participants who were randomized to study drug; six ECOG scores were missing at the March 2008 cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) | 10.1 weeks |
| Placebo Plus Dexamethasone | Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) | 12.3 weeks |
p-value: 0.35995% CI: [0.866, 1.486]Log Rank
Post Hoc
Kaplan-Meier Estimate of Duration of Response
Duration of response was calculated for responders and defined as the time from the first observation of a response (e.g., the first time that the appropriate decrease in M-protein level was observed for confirmed responders) to the first documented progression or relapse. Response duration was censored at the last adequate assessment showing evidence of no progression.
Time frame: Up to data cut off of 03 August 2005; up to 24 months
Population: Intent to Treat population includes all participants who were randomized to study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Kaplan-Meier Estimate of Duration of Response | 67.6 weeks |
| Placebo Plus Dexamethasone | Kaplan-Meier Estimate of Duration of Response | 33.3 weeks |
p-value: 0.02195% CI: [0.338, 0.921]Log Rank
Post Hoc
Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008)
Duration of response was calculated for responders and defined as the time from the first observation of a response (e.g., the first time that the appropriate decrease in M-protein level was observed for confirmed responders) to the first documented progression or relapse. Response duration was censored at the last adequate assessment showing evidence of no progression.
Time frame: Up to data cut off of 03 Mar 2008; up to 51 months
Population: Intent to Treat population includes all participants who were randomized to study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide Plus Dexamethasone | Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008) | 68.1 weeks |
| Placebo Plus Dexamethasone | Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008) | 33.3 weeks |
p-value: 0.03295% CI: [0.398, 0.964]Log Rank