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.

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

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan, 734-8551
    • Celgene Clinical Site
  • Kyoto, Japan, 601-1495
    • Celgene Clinical Site
  • Osaka, Japan, 543-8555
    • Celgene Clinical Site
  • Shizuoka, Japan, 420-8527
    • Celgene Clinical Site
  • Tochigi
    • Shimono, Tochigi, Japan, 329-0498
      • Celgene Clinical Site
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Celgene Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide; 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; 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).; Other Names: CC-5013

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Masaaki Takatoku, MD, Celgene Corporation

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2007
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 19, 2008
• First Posted (Estimate): December 22, 2008

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Lenalidomide; Myelodysplastic Syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: CC-5013-MDS-007