Back to resultsStudy 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.
Primary Purpose
Myelodysplastic Syndromes
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Myelodysplastic Syndromes, Lenalidomide
Eligibility Criteria
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)
Sites / Locations
- Celgene Clinical Site
- Celgene Clinical Site
- Celgene Clinical Site
- Celgene Clinical Site
- Celgene Clinical Site
- Celgene Clinical Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lenalidomide
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
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).
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).
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.
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).
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).
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00812968
Brief Title
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.
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
September 1, 2007 (Actual)
Primary Completion Date
September 1, 2010 (Actual)
Study Completion Date
September 1, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
Myelodysplastic Syndromes, Lenalidomide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lenalidomide
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
CC-5013
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AE)
Description
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.
Time Frame
After the first study dose until 28 days after completion of/discontinuation from the study (maximum time on study was 155 weeks).
Secondary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Lenalidomide
Description
Maximum observed plasma concentration of lenalidomide after a single dose on Day and after multiple doses (Day 4).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Time to Maximum Plasma Concentration (Tmax) of Lenalidomide
Description
Time to maximum observed plasma concentration of lenalidomide after a single dose on Day 1 and multiple doses (Day 4).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Lenalidomide
Description
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).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCτ) of Lenalidomide
Description
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).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose.
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Lenalidomide
Description
Area under the plasma concentration-time curve from time zero to infinity (AUC∞) of lenalidomide after a single dose on Day 1.
Time Frame
Day 1 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose.
Title
Terminal Half-life (T1/2) of Lenalidomide
Description
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).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Apparent Volume of Distribution (VzF) of Lenalidomide
Description
Apparent volume of distribution of lenalidomide after a single dose on Day 1 and multiple doses (Day 4).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Apparent Total Plasma Clearance (CL/F) of Lenalidomide
Description
Apparent total plasma clearance (CL/F) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Apparent Terminal Elimination Rate Constant of Lenalidomide
Description
Apparent terminal elimination rate constant of lenalidomide determined after a single dose on Day 1 and multiple doses (Day 4).
Time Frame
Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
Title
Number of Participants With a Erythroid Response
Description
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.
Time Frame
Response was assessed every 28 days through Week 156.
Title
Time to Erythroid Response
Description
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.
Time Frame
From the first dose of study drug through Week 156
Title
Duration of Erythroid Response
Description
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.
Time Frame
From the first dose of study drug through Week 156
Title
Change From Baseline in Hemoglobin Concentration
Description
Change in hemoglobin concentration from Baseline to the maximum observed value during the major erythroid response period for major erythroid responders.
Time Frame
Baseline and from Day1 until the maximum observed value (up to 155 weeks)
Title
Number of Participants With a Neutrophil Response
Description
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.
Time Frame
Response was assessed every 28 days through Week 156
Title
Number of Participants With a Platelet Response
Description
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.
Time Frame
Response was assessed every 28 days through Week 156
Title
Number of Participants With a Cytogenetic Response
Description
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.
Time Frame
Response was assessed every 12 weeks through Week 156
Title
Change From Baseline in Percentage of Bone Marrow Erythroblasts
Description
Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section.
Time Frame
Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169).
Title
Percentage of Bone Marrow Myeloblasts
Description
Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section.
Time Frame
Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169).
Title
Percentage of Bone Marrow Promyelocytes
Description
Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section.
Time Frame
Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Masaaki Takatoku, MD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Celgene Clinical Site
City
Shimono
State/Province
Tochigi
ZIP/Postal Code
329-0498
Country
Japan
Facility Name
Celgene Clinical Site
City
Shibuya-ku
State/Province
Tokyo
ZIP/Postal Code
150-8935
Country
Japan
Facility Name
Celgene Clinical Site
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Celgene Clinical Site
City
Kyoto
ZIP/Postal Code
601-1495
Country
Japan
Facility Name
Celgene Clinical Site
City
Osaka
ZIP/Postal Code
543-8555
Country
Japan
Facility Name
Celgene Clinical Site
City
Shizuoka
ZIP/Postal Code
420-8527
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
22172461
Citation
Matsuda A, Taniwaki M, Jinnai I, Harada H, Watanabe M, Suzuki K, Yanagita S, Suzuki T, Yoshida Y, Kimura A, Tsudo M, Tohyama K, Takatoku M, Ozawa K. Morphologic analysis in myelodysplastic syndromes with del(5q) treated with lenalidomide. A Japanese multiinstitutional study. Leuk Res. 2012 May;36(5):575-80. doi: 10.1016/j.leukres.2011.11.011. Epub 2011 Dec 15.
Results Reference
background
PubMed Identifier
19705057
Citation
Harada H, Watanabe M, Suzuki K, Yanagita S, Suzuki T, Yoshida Y, Kimura A, Tsudo M, Matsuda A, Tohyama K, Taniwaki M, Takeshita K, Takatoku M, Ozawa K. Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes with a deletion 5q abnormality. Int J Hematol. 2009 Oct;90(3):353-360. doi: 10.1007/s12185-009-0400-8. Epub 2009 Aug 25.
Results Reference
result
Learn more about this trial
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.
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