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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00812968
First received: December 17, 2008
Last updated: September 30, 2013
Last verified: September 2013
  Purpose

The purpose of this clinical experience study is to determine whether lenalidomide is safe and effective, and the process by which the drug is absorbed, distributed, metabolized, and eliminated by the body (pharmacokinetics) in Japanese patients with low- or intermediate-1-risk MDS associated with a deletion 5(q31-33) abnormality and symptomatic anemia.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Single-arm Study to Assess the Safety, Pharmacokinetics and Efficacy of Lenalidomide in Japanese Patients With Low- or Intermediate-1-risk Myelodysplastic Syndromes Associated With a Deletion 5(q31-33) Abnormality and Symptomatic Anemia

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AE) [ Time Frame: From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study was 155 weeks). ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ 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. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Response was assessed every 28 days through Week 156. ] [ Designated as safety issue: No ]

    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 Frame: From the first dose of study drug through Week 156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the first dose of study drug through Week 156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and from Day1 until the maximum observed value (up to 155 weeks) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Response was assessed every 28 days through Week 156 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Response was assessed every 28 days through Week 156 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Response was assessed every 12 weeks through Week 156 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169). ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169). ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169). ] [ Designated as safety issue: No ]
    Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section.


Enrollment: 11
Study Start Date: August 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide
10 mg of lenalidomide was administered orally once daily on Days 1 to 21 of every 28-day cycle. Treatment continued until disease progression or relapse following an erythroid improvement was documented, any of the criteria for treatment discontinuation was violated, or lenalidomide became commercially available for the treatment of MDS associated with a del (5q) cytogenetic abnormality, for up to 156 weeks (3 years).
Drug: Lenalidomide
Capsules for oral administration
Other Names:
  • CC-5013
  • Revlimid

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 hemoglobin 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 patient 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 (50 x 10^9/L)
    • Serum creatinine > 2.5 mg/dL
    • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3.0 x Upper Limit of Normal (ULN)
  • Chronic myelomonocytic leukemia (CMMoL), defined as a white blood cell (WBC) count of ≥ 12,000/µL (12 × 10^9/L).
  • Prior history of malignancy other than MDS except for basal cell or squamous cell carcinoma, carcinoma in situ of the cervix or breast, or incidental histological finding of prostate cancer (TNM [tumor, node, metastasis] stage of T1a or T1b) unless the patient had been free of disease for ≥ 3 years.
  • Prior history of deep vein thrombosis (DVT) or pulmonary embolus (PE) within the past 3 years of starting study drug.
  • Tuberculous diseases, herpes simplex keratitis, systemic fungal infection, or other active infectious diseases.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00812968

Locations
Japan
Celgene Clinical Site
Shimotsuke, Tochigi, Japan, 329-0498
Celgene Clinical Site
Shibuya-ku, Tokyo, Japan, 150-8935
Celgene Clinical Site
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
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Masaaki Takatoku, MD Celgene Corporation
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00812968     History of Changes
Other Study ID Numbers: CC-5013-MDS-007
Study First Received: December 17, 2008
Results First Received: September 30, 2013
Last Updated: September 30, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
Japan: Ministry of Health, Labor and Welfare

Keywords provided by Celgene Corporation:
Myelodysplastic Syndromes
Lenalidomide

Additional relevant MeSH terms:
Congenital Abnormalities
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014