Lenalidomide Safety/Efficacy in Myelodysplastic Syndromes (MDS) Associated With a Deletion (Del)(5q) Cytogenetic Abnormality

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00065156
First received: July 17, 2003
Last updated: October 5, 2011
Last verified: October 2011
  Purpose

This study is a multicenter, single-arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion-dependent subjects with low- or intermediate-1-risk Myelodysplastic Syndromes (MDS) associated with a del (5q31-33) cytogenetic abnormality. Screening procedures will take place within 28 days of the first day of lenalidomide treatment. Subjects will receive lenalidomide in 28-day cycles for up to 6 cycles, or until bone marrow disease progression or progression/relapse following erythroid hematologic improvement is documented. Study visits will occur every cycle (every 28 days) and laboratory monitoring to assess hematological parameters will occur every 14 days. Safety and efficacy assessments to be performed during the study are outlined in the Schedule of Study Assessments.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of Lenalidomide Monotherapy in Red Blood Cell Transfusion-dependent Subjects With Myelodysplastic Syndromes Associated With a Del(5q) Cytogenetic Abnormality.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Number of participants who achieved RBC-transfusion independence, which was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (eg, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin.


Secondary Outcome Measures:
  • Participants With Adverse Experiences [ Time Frame: Up to 2 Years ] [ Designated as safety issue: No ]

    Counts of study participants who had adverse events (AEs) during the study. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator.

    The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE.


  • Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study [ Time Frame: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years) ] [ Designated as safety issue: No ]
    A participant was categorized as having a transfusion reduction response if there was a ≥ 50% decrease from pretreatment transfusion requirements (before the start of the study mediation) compared to any consecutive 56 days during the study (i.e. post treatment).

  • Time to Transfusion Independence [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Time to transfusion independence was defined as the day of the first dose of study drug to the first day of the first 56-day RBC transfusion-free period.

  • Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Participants who relapsed required a transfusion after the period of transfusion independence. Participants who maintained transfusion independence did not require a transfusion during the remainder of the study.

  • Kaplan Meier Estimate for Duration of Transfusion Independence Response [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Duration of response is measured from the first of the consecutive 56 days during which the participant was free of RBC transfusions to the date of the first RBC transfusion after this period. Duration of response was censored at the date of last visit for participants who maintained transfusion independence.

  • Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders [ Time Frame: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years) ] [ Designated as safety issue: No ]
    The change from baseline in hemoglobin for participants who became RBC-transfusion independent. The maximum hemoglobin value obtained during the response period is used in the calculation of change from baseline.

  • Participant Counts of Cytogenetic Response [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

    Participants deemed evaluable by the central cytogenetic review had their cytogenetic response categorized as major or minor. A major cytogenetic response was defined as ≥ 20 metaphases recorded at baseline, and at least

    1 post baseline evaluation with ≥ 20 metaphases analyzed with no abnormal metaphases observed. A minor cytogenetic response was defined as ≥ 20 metaphases analyzed at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with a ≥ 50% reduction in the proportion of hematopoietic cells with cytogenetic abnormalities compared with baseline.


  • Participant Counts of Platelet Response [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

    Major platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3 in all values within 56 days of start of treatment, an absolute increase of ≥30,000/mm^3 sustained for ≥56 consecutive days. In platelet transfusion-dependent participants, a major response was stabilization of platelet counts and platelet transfusion independence.

    Minor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3, a ≥ 50% increase in platelet count with a net increase >10,000/mm^3 for a consecutive 56-day period in the absence of platelet transfusions.


  • Participant Counts of Absolute Neutrophil Count (ANC) Response [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

    Major neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3 in all values obtained within 56 days of start of treatment, a ≥ 100% increase or an absolute increase of

    ≥ 500/mm^3, whichever was greater (at least to be ≥ 500/mm^3), sustained for 56 consecutive days. Minor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3, an increase in ANC concentration of ≥ 100% sustained for 56 consecutive days.


  • Participants With Complete or Partial Bone Marrow Improvement [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Bone marrow aspirates were assessed by a central reviewer. A complete bone marrow improvement required a baseline French-American-British (FAB) classification (see Baseline Characteristics) of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) and a during study assessment of no MDS. A partial bone marrow improvement reflected an improved FAB classification compared to baseline (e.g. RARS to RA) but evidence of MDS continued to exist.

  • Participants With Bone Marrow Progression [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

    Bone marrow aspirate was assessed by a central reviewer. Progression is represented in two categories according to changes from baseline in French-American-British (FAB) classification (see Baseline Characteristics):

    • Baseline classification of refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) to a during treatment (plus 30 days) classification of refractory anemia with excess blasts (RAEB).
    • Any baseline FAB classification to a during treatment (plus 30 days) classification of acute myeloid leukemia (AML).


Enrollment: 148
Study Start Date: June 2003
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide Drug: lenalidomide
10 mg orally once daily for 21 days out of a 28-day cycle (syncopated); subsequently amended (Amendment 1, dated 27 August 2003) to employ a continuous dosage regimen in which 10 mg was taken once daily for 28 day cycles (continuous). Subjects who initially began a syncopated regimen and who did not experience a dose-limiting adverse event were allowed to switch to the continuous regimen.
Other Names:
  • lenalidomide
  • CC-5013

  Eligibility

Ages Eligible for Study:   18 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 18 years or older at the time of signing the informed consent
  • Must be able to adhere to the study visit schedule and other protocol requirements.
  • Diagnosis of low or intermediate-1-risk International Prognostic Scoring System (IPSS) Myelodysplastic Syndromes (MDS) without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.
  • Red blood cell (RBC) transfusion-dependent anemia defined as having received greater than or equal to 2 units of RBCs within 8 weeks of the first day of study drug treatment.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
  • Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug.
  • Sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.
  • WCBP must agree to have pregnancy tests every 4 weeks while on study drug.

Exclusion Criteria:

  • Pregnant or lactating females
  • Prior therapy with lenalidomide.
  • An abnormality of chromosome 5 involving a deletion between bands q31 and q33.
  • Lab Abnormality: Absolute neutrophil count (ANC) <500 cell/mm^3 (0.5*10^9/L)
  • Lab Abnormality: Platelet count <50,000/mm^3 (50*10^9/L)
  • Lab Abnormality: Serum creatinine >2.5 mg/dL (221 mmol/L)
  • Lab Abnormality: Serum total bilirubin >2.0 mg/dL (34 mmol/L)
  • Prior greater than or equal to grade 3 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) allergic reaction/hypersensitivity to thalidomide.
  • Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding
  • If a marrow aspirate is not evaluable for storage iron, transferrin saturation must be > 20% and serum ferritin not less than 50 ng/mL
  • Use of hematopoietic growth factors within 7 days of the first day of study drug treatment.
  • Prior greater than or equal to grade 3 NCI CTC rash or any desquamation (blistering) while taking thalidomide.
  • Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to >10 mg/day of prednisone) within 28 days of the first day of study drug treatment.
  • Use of experimental or standard drugs (i.e. chemotherapeutic, immunosuppressive, and cytoprotective agents) for the treatment of MDS within 28 days of the first day of study drug treatment.
  • Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for greater than or equal to 3 years.
  • Use of any other experimental therapy within 28 days of the first day of study drug treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00065156

  Show 32 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Alan F List, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Publications:
A.F. List, et.al. Results of the MDS-002 and -003 international phase II studies evaluating lenalidomide (CC-5013; Revlimid) in the treatment of transfusion-dependent (TD) patients with myelodysplastic syndrome (MDS). European Hematology Association 10th Conference June 2-5, 2005 Abstract #0772

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00065156     History of Changes
Obsolete Identifiers: NCT00074126
Other Study ID Numbers: CC-5013-MDS-003
Study First Received: July 17, 2003
Results First Received: August 31, 2009
Last Updated: October 5, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
MDS
CC-5013
Revlimid
Celgene

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

ClinicalTrials.gov processed this record on August 20, 2014