Study of CC-5013 to Evaluate Safety, Pharmacokinetics and Effectiveness for Japanese Patients With Symptomatic Anemia Associated With Myelodysplastic Syndrome With a Del(5)(q31-33) Abnormality.

Study Overview
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Brief Summary
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The purpose of this clinical experience study is to determine whether CC-5013 is safe and effective (to include studying the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body [pharmacokinetics]) in Japanese subjects with low- or intermediate-1-risk MDS (IPSS risk categories) associated with a deletion 5(q31-33) abnormality and symptomatic anemia.

Official Title
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A Multicenter, Single-arm Study to Assess the Safety, Pharmacokinetics and Efficacy of Lenalidomide in Japanese Subjects With Low- or Intern=Mediate-1-risk Myelodysplastic Syndromes (MDS) Associated With a Deletion 5 (q31-33) Abnormality and Symptomatic Anemia

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must understand and voluntarily sign an informed consent form. Age ≥ 20 years at the time of signing the informed consent form. Must be able to adhere to the study visit schedule and other protocol requirements. Diagnosis of Myelodysplastic Syndrome (MDS) that meets International Prognostic Scoring System (IPSS) criteria for low- or intermediate-1-risk disease associated with a deletion 5(q31-33) abnormality Symptomatic anemia secondary to MDS defined as:Untransfused Hb level < 10.0 g/dL and a Functional Assessment of Cancer Therapy (FACT)-anemia subscale score of ≤ 74 or Transfusion dependent anemia Exclusion Criteria: Pregnant or lactating females. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. Prior therapy with lenalidomide. Patients with any of the following laboratory abnormalities within 14 days of starting study drug: Absolute Neutrophil Count (ANC) < 750 cells/μL (0.75 x 10^9/L) Platelet count < 50,000/μL (50x10^9/L) Serum creatinine > 2.5 mg/dL Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3.0 x Upper Limit of Normal (ULN)

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<br>Oral 10mg daily on Days 1-21 days every 28 days until disease progression/relapse or CC-5013 is permanently discontinued for any reason for up to 156 weeks (3 years). | Drug: Lenalidomide<br>* Oral 10mg daily on Days 1-21 days every 28 days until disease progression/relapse or CC-5013 is permanently discontinued for any reason for up to 156 weeks (3 years).<br>* Other names: CC-5013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) | An AE that resulted in any of the following outcomes was defined as a serious adverse event (SAE): Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. | After the first study dose until 28 days after completion of/discontinuation from the study (maximum time on study was 155 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Lenalidomide | Maximum observed plasma concentration of lenalidomide after a single dose on Day and after multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Time to Maximum Plasma Concentration (Tmax) of Lenalidomide | Time to maximum observed plasma concentration of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Lenalidomide | Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUCt) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCτ) of Lenalidomide | Area under the plasma concentration-time curve over the dosing interval (AUCτ) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose. | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Lenalidomide | Area under the plasma concentration-time curve from time zero to infinity (AUC∞) of lenalidomide after a single dose on Day 1. | Day 1 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose. | 
| Terminal Half-life (T1/2) of Lenalidomide | The apparent terminal half-life is the time required for plasma concentration to decrease by 50% after pseudo-equilibrium of distribution has been reached, and calculated as the natural logarithm of 2 (0.693) / Apparent terminal rate constant (λz). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Apparent Volume of Distribution (VzF) of Lenalidomide | Apparent volume of distribution of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Apparent Total Plasma Clearance (CL/F) of Lenalidomide | Apparent total plasma clearance (CL/F) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Apparent Terminal Elimination Rate Constant of Lenalidomide | Apparent terminal elimination rate constant of lenalidomide determined after a single dose on Day 1 and multiple doses (Day 4). | Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. | 
| Number of Participants With a Erythroid Response | Erythroid response was determined using the International Working Group (IWG) 2000 criteria, categorized as a major response or minor response. A major response in patients with transfusion-dependent anemia (receiving ≥ 4.5 units of red blood cell (RBC) transfusion during 56 consecutive days at Baseline) is defined as RBC transfusion independence accompanied by a ≥1.0 g/dL increase from Baseline in hemoglobin sustained for 56 days consecutively during the treatment period. In patients with transfusion-independent anemia with hemoglobin < 10 g/dL at Baseline a major response is defined as a > 2.0 g/dL increase from Baseline in hemoglobin sustained for consecutive 56 days. Minor response in patients with transfusion-dependent anemia defined as ≥ 50% decrease from Baseline in transfusion requirements sustained for consecutive 56 days, and in transfusion-independent patients as 1.0 to 2.0 g/dL increase from Baseline in hemoglobin sustained for consecutive 56 days. | Response was assessed every 28 days through Week 156. | 
| Time to Erythroid Response | Time to erythroid response was calculated as the time from the first dose of study drug to the start of the first major or minor erythroid response. Similarly, time to major erythroid response was calculated as the time from the first dose of study drug to the start of the first major erythroid response. | From the first dose of study drug through Week 156 | 
| Duration of Erythroid Response | Duration of erythroid response was calculated as the time from the start of the first major or minor erythroid response to the end of the response. Similarly, duration of major erythroid response was calculated as the time from the start of the first major erythroid response to the end of the response. Response duration was censored at the last adequate assessment for patients who maintained response. | From the first dose of study drug through Week 156 | 
| Change From Baseline in Hemoglobin Concentration | Change in hemoglobin concentration from Baseline to the maximum observed value during the major erythroid response period for major erythroid responders. | Baseline and from Day1 until the maximum observed value (up to 155 weeks) | 
| Number of Participants With a Neutrophil Response | Neutrophil response was determined using the IWG (2000) criteria. A major response for participants with a Baseline neutrophil count < 1,500/mm^3 is defined as a ≥ 100% increase or a ≥ 500/mm^3 increase, whichever is greater, sustained for consecutive 56 days during the treatment period. A minor response for participants with a Baseline neutrophil count < 1,500/mm^3 is defined as a ≥ 100% increase, but an absolute increase < 500/mm^3, sustained for consecutive 56 days during the treatment period. | Response was assessed every 28 days through Week 156 | 
| Number of Participants With a Platelet Response | Platelet response was determined using the IWG (2000) criteria. Major response in patients with Baseline platelet count < 100,000/mm^3 is defined as a ≥ 30,000/mm^3 increase sustained for consecutive 56 days during the treatment period. In platelet-transfusion-dependent patients at Baseline a major response is defined as stabilization of platelet counts and platelet transfusion independence sustained for consecutive 56 days during the treatment period. Minor response in patients with Baseline platelet count < 100,000/mm^3 is defined as a ≥ 50% increase in platelet count with an absolute increase > 10,000/mm^3 and < 30,000/mm^3 sustained for consecutive 56 days during the treatment period. | Response was assessed every 28 days through Week 156 | 
| Number of Participants With a Cytogenetic Response | Cytogenetic (chromosome structure) abnormalities were assessed by a central cytogenetic reviewer based on prints and cytogenetic reports of the bone marrow sample from the central laboratory. Cytogenetic response was determined using the IWG (2000) criteria and categorized as either a major response or minor response. Twenty metaphases were analyzed for the determination of cytogenetic response. A major response was defined as no detectable cytogenetic abnormality, if an abnormality was present at Baseline, sustained for consecutive 56 days during the treatment period. A minor response was defined as ≥ 50% reduction from Baseline in abnormal metaphases sustained for consecutive 56 days during the treatment period. | Response was assessed every 12 weeks through Week 156 | 
| Change From Baseline in Percentage of Bone Marrow Erythroblasts | Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section. | Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169). | 
| Percentage of Bone Marrow Myeloblasts | Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section. | Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169). | 
| Percentage of Bone Marrow Promyelocytes | Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section. | Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, Lenalidomide