A Study of 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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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.

Official Title
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The Official Title is A Multi-center, 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 plus dexamethasone
* Drug: Dexamethasone plus Placebo


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. 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.

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 plus dexamethasone<br>Arm A: Oral CC-5013 is initiated on Day 1 of Cycle 1 at a dose of 25 mg daily for 21 days every 28 days. Therefore, the subject will take a placebo identical in appearance to the CC-5013 capsule for week 4 of every 28 days. 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 CC-5013 placebo capsules will be administered for 28 days of every cycle. | Drug: CC-5013 plus dexamethasone<br>* 25 mg daily for 21 days every 28 days.<br>* Other names: lenalidomide;|
| Experimental: Dexamethasone plus placebo<br>Arm B: 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. | Drug: Dexamethasone plus Placebo<br>* 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.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From randomization up to cut-off date of 03 August 2005; up to 24 months | 
| 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. | From randomization up to cut-off date of 02 March 2008; up to 51 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Randomization to data cut off of 03 August 2005; up to 24 months | 
| 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. | Randomization to data cut off of 02 March 2008; up to 51 months | 
| 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. | Randomization to 03 August 2005; up to 24 months | 
| 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. | Randomization to data cut-off of 02 Mar 2008; up to 51 months | 
| 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. | 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 | 
| 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). | Up to unblinding data cut off of 03 August 2005; up to 24 months | 
| 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. | Randomization to cut off date of 03 August 2005; up to 24 months | 
| 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. | Randomization to cut off date of 02 March 2008; up to 51 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Celgene, Revlimid, CC-5013