Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Refractory and Relapsed, Revlimid, CC5013
Brief summary
Randomized subjects will receive CC-5013 plus high-dose dexamethasone or placebo appearing identical to CC-5013 plus high-dose dexamethasone in 4-week cycles. Each subject will participate in a treatment phase and a follow-up phase.
Detailed description
This was a phase 3, multicenter, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of CC-5013 plus oral pulse high-dose dexamethasone and oral pulse high-dose dexamethasone therapy alone in subjects with relapsed or refractory multiple myeloma. Eligible subjects were randomized in a 1:1 ratio to 1 of 2 treatment groups: Subjects in the CC-5013/Dex treatment group took 25 mg of CC-5013 orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28-day cycle; Subjects in the Placebo/Dex treatment group took 1 placebo capsule on Days 1 to 28 of each 28-day cycle. Subjects in both treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy. Beginning with Cycle 5, the dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 for the remaining cycles.
Interventions
DRUGCC-5013
Subjects in the CC-5013/Dex treatment group took 25 mg of lenalidomide orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28-day cycle.
DRUGDexamethasone
Subjects in the CC-5013/Dex and Placebo/Dex treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy. Beginning with Cycle 5, the dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 for the remaining cycles.
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. * No more than 3 previous anti-myeloma regimens * No high-dose dexamethasone (total monthly dose of dexamethasone greater than 200 mg) within 6 months of study randomization. * Measurable levels of myeloma paraprotein in serum or urine (24-hour collection sample).
Exclusion criteria
* Prior development of disease progression during high-dose dexamethasone containing therapy. * Laboratory abnormalities: Absolute neutrophil count less than 1,000 cells/mm cubed * Laboratory abnormalities: Platelet count less than 75,000/mm cubed * Laboratory abnormalities: Serum creatinine greater than 2.5 mg/dL * Laboratory abnormalities: Serum glutamic oxaloacetic transaminase (SGOT, aspartate transaminase \[AST\]) or serum glutamic pyruvic transaminase (SGPT, alanine transaminase \[ALT\])greater than 3.0 x upper limit of normal * Laboratory abnormalities: Serum total bilirubin greater than 2.0 mg/dL * Prior history of malignancies other than multiple myeloma unless the subject has been free of the disease for greater than or equal to 5 years. * Known hypersensitivity to thalidomide or dexamethasone. * Development of a desquamating rash while taking thalidomide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tumor Progression (TTP) | 60 weeks (median Time To Progression of CC-5013/Dex treatment group) | Time to progression (TTP) was calculated as the time from randomization to the first documentation of progressive disease based on the myeloma response determination criteria developed by Bladé et. al., Br J Haematol 1998; 102:1115-1123. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 170 weeks (median overall survival of CC-5013/Dex treatment group) | Overall survival was calculated as the time from randomization to death from any cause. |
| Myeloma Response | Up to Unblinding (07 Jun 2005) | The overall confirmed response that was maintained for ≥6 weeks. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens. |
| Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.) | 30 weeks (mean time to first worsening of ECOG performance status for CC-5013/Dex treatment group) | The time to first worsening on the ECOG Performance Scale was calculated as the time from randomization to the date of the first worsening compared to the last ECOG evaluation obtained prior to randomization. |
Countries
Canada, United States
Participant flow
Recruitment details
Subjects in the Placebo/Dex treatment group did not continue participation beyond the period Up To Unblinding (07 Jun 2005). Only subjects in the CC-5013/Dex treatment group participated in the period Extended Follow-up Cutoff (23 Jul 2008).
Pre-assignment details
Only subjects in the CC-5013/Dex treatment group participated in the period Extended Follow-up Cutoff (23 Jul 2008). Data for the period Extended Follow-up Cutoff (23 Jul 2008) subsumes data for the period Up To Unblinding (07 Jun 2005).
Participants by arm
| Arm | Count |
|---|---|
| CC-5013/Dex CC-5013 (lenalidomide) plus oral high-dose dexamethasone | 177 |
| Placebo/Dex Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone | 176 |
| Total | 353 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extended Follow-up Cutoff (23 Jul 2008) | Adverse Event | 44 | 0 |
| Extended Follow-up Cutoff (23 Jul 2008) | Death | 5 | 0 |
| Extended Follow-up Cutoff (23 Jul 2008) | Lack of Efficacy | 3 | 0 |
| Extended Follow-up Cutoff (23 Jul 2008) | Other | 21 | 0 |
| Extended Follow-up Cutoff (23 Jul 2008) | Progression of disease | 87 | 0 |
| Extended Follow-up Cutoff (23 Jul 2008) | Withdrawal by Subject | 11 | 0 |
| Final Follow-up | Adverse Event | 1 | 0 |
| Final Follow-up | Transferred into expanded access study. | 3 | 0 |
| Final Follow-up | Transferred into RevAssist Program | 2 | 0 |
| Up to Unblinding (07 Jun 2005) | Adverse Event | 35 | 18 |
| Up to Unblinding (07 Jun 2005) | Death | 2 | 1 |
| Up to Unblinding (07 Jun 2005) | Lack of Efficacy | 3 | 5 |
| Up to Unblinding (07 Jun 2005) | Other | 8 | 7 |
| Up to Unblinding (07 Jun 2005) | Progression of disease | 57 | 124 |
| Up to Unblinding (07 Jun 2005) | Withdrawal by Subject | 8 | 8 |
Baseline characteristics
| Characteristic | CC-5013/Dex | Placebo/Dex | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 83 Participants | 73 Participants | 156 Participants |
| Age, Categorical Between 18 and 65 years | 94 Participants | 103 Participants | 197 Participants |
| Age, Continuous | 63.3 years STANDARD_DEVIATION 9.84 | 62.5 years STANDARD_DEVIATION 9.81 | 62.9 years STANDARD_DEVIATION 9.81 |
| Region of Enrollment Canada | 35 participants | 26 participants | 61 participants |
| Region of Enrollment United States | 142 participants | 150 participants | 292 participants |
| Sex: Female, Male Female | 71 Participants | 72 Participants | 143 Participants |
| Sex: Female, Male Male | 106 Participants | 104 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 177 / 177 | 175 / 175 |
| serious Total, serious adverse events | 111 / 177 | 90 / 175 |
Outcome results
Primary
Time to Tumor Progression (TTP)
Time to progression (TTP) was calculated as the time from randomization to the first documentation of progressive disease based on the myeloma response determination criteria developed by Bladé et. al., Br J Haematol 1998; 102:1115-1123.
Time frame: 60 weeks (median Time To Progression of CC-5013/Dex treatment group)
Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CC-5013/Dex | Time to Tumor Progression (TTP) | 60.1 Weeks |
| Placebo/Dex | Time to Tumor Progression (TTP) | 20.1 Weeks |
Secondary
Myeloma Response
The overall confirmed response that was maintained for ≥6 weeks. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens.
Time frame: Up to Unblinding (07 Jun 2005)
Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized. Results reported (Response) are numbers of subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC-5013/Dex | Myeloma Response | 107 Participants |
| Placebo/Dex | Myeloma Response | 34 Participants |
Secondary
Overall Survival
Overall survival was calculated as the time from randomization to death from any cause.
Time frame: 170 weeks (median overall survival of CC-5013/Dex treatment group)
Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CC-5013/Dex | Overall Survival | 170.1 Weeks |
| Placebo/Dex | Overall Survival | 136.4 Weeks |
Secondary
Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.)
The time to first worsening on the ECOG Performance Scale was calculated as the time from randomization to the date of the first worsening compared to the last ECOG evaluation obtained prior to randomization.
Time frame: 30 weeks (mean time to first worsening of ECOG performance status for CC-5013/Dex treatment group)
Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CC-5013/Dex | Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.) | 29.9 Weeks | Standard Deviation 30.02 |
| Placebo/Dex | Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.) | 15.0 Weeks | Standard Deviation 16.98 |