A Phase 2 Study of Lenalidomide to Evaluate the Efficacy in Japanese Patients With Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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To determine the efficacy of lenalidomide in combination with low-dose dexamethasone in Japanese subjects with previously untreated multiple myeloma.

Official Title
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A Phase 2, Multicenter, Open-label, Single Arm Study of Lenalidomide (CC-5013) in Combination With Low-dose Dexamethasone in Japanese Patients With Previously Untreated Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide plus dexamethasone<br>Lenalidomide plus low-dose dexamethasone | Drug: Lenalidomide<br>* 25 mg oral lenalidomide once daily on Days 1-21 of each 28-day cycle<br>* Other names: Revlimid;Drug: dexamethasone<br>* 40 mg oral dexamethasone once daily on Days 1, 8, 15 and 22 of each 28-day cycle<br>* Other names: LenaDex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From first dose until the data cut-off date of 15 July 2014. Median time on follow-up was 61.6 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 
| 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. | 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. | 
| 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. | 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. | 
| 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. | 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 | 
| 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lenalidomide, dexamethasone, newly diagnosed multiple myeloma