CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter, Randomized, Parallel-Group, Double-blind, Placebo-controlled Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: CC-5013
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC-5013/Dex<br>CC-5013 (lenalidomide) plus oral high-dose dexamethasone | Drug: CC-5013<br>* 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.<br>* Other names: Revlimid;Drug: Dexamethasone<br>* 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.<br>* Other names: Decadron;|
| Experimental: Placebo/Dex<br>Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone | Drug: Dexamethasone<br>* 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.<br>* Other names: Decadron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 60 weeks (median Time To Progression of CC-5013/Dex treatment group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was calculated as the time from randomization to death from any cause. | 170 weeks (median overall survival of CC-5013/Dex treatment group) | 
| 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. | Up to Unblinding (07 Jun 2005) | 
| 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. | 30 weeks (mean time to first worsening of ECOG performance status for CC-5013/Dex treatment group) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Refractory and Relapsed, Revlimid, CC5013