Clinical Trials /

A Study to Evaluate the Efficacy and Safety of Lenalidomide as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Following Second Line Therapy

NCT00774345

Description:

The purpose of this study is to determine if lenalidomide (Revlimid®) is safe and effective as a maintenance therapy at improving further the quality of the response you achieved with your last therapy and at prolonging the duration of your response. This study will compare the effects (good and bad) of lenalidomide with the dummy drug.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

A Study to Evaluate the Efficacy and Safety of <span class="go-doc-concept go-doc-intervention">Lenalidomide</span> as Maintenance Therapy for Patients With B-Cell <span class="go-doc-concept go-doc-disease">Chronic Lymphocytic Leukemia</span> (<span class="go-doc-concept go-doc-disease">CLL</span>) Following Second Line Therapy

Title

  • Brief Title: A Study to Evaluate the Efficacy and Safety of Lenalidomide as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Following Second Line Therapy
  • Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid) as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia Following Second-Line Therapy (The Continuum Trial)
  • Clinical Trial IDs

    NCT ID: NCT00774345

    ORG ID: CC-5013-CLL-002

    Trial Conditions

    B-cell Chronic Lymphocytic Leukemia

    Trial Interventions

    Drug Synonyms Arms
    Lenalidomide Revlimid 1
    Placebo 2

    Trial Purpose

    The purpose of this study is to determine if lenalidomide (Revlimid) is safe and effective
    as a maintenance therapy at improving further the quality of the response you achieved with
    your last therapy and at prolonging the duration of your response. This study will compare
    the effects (good and bad) of lenalidomide with the dummy drug.

    Detailed Description

    This is a phase 3, randomized (computer assigned by chance to treatment arm), study being
    completed an multiple sites to compare the safety and efficacy (how well a drug works) of
    lenalidomide maintenance therapy to placebo (dummy capsule that contains no lenalidomide or
    active substances) maintenance therapy.

    Patients are assigned by a computer with a 50/50 chance to receive placebo or lenalidomide
    study treatment. Study drug will be taken once each day until the patient discontinues the
    study. Patients will remain on study drug until progression of disease.

    Patients will visit their study doctor every 28 days until disease progression to complete
    safety and efficacy assessments. Quality of life assessments will be completed every other
    month. If a patient who discontinue study drug prior to disease progression (i.e. due to an
    adverse reaction to the study drug), they will continue to visit the study doctor each month
    to complete the efficacy assessments up to progression of disease. Safety assessments may
    include laboratory blood tests, ECG tests and questions about any medical conditions or side
    effects experienced during the study. Efficacy assessments may include laboratory blood
    tests and focused physical exams.

    Computed tomography (CT) scans along with blood tests and bone marrow samples will be
    collected to confirm if a patient has improvement of response while on study.

    After disease progression, patients will be contacted every 12 weeks for survival
    information, next CLL treatments and quality of life questions.

    Trial Arms

    Name Type Description Interventions
    1 Experimental Lenalidomide po qd on days 1-28 of a 28 day cycle Lenalidomide
    2 Placebo Comparator Placebo capsules given orally on days 1-28 of a 28 day cycle Placebo

    Eligibility Criteria

    Inclusion Criteria:

    1. Must understand and voluntarily sign an informed consent form.

    2. Must be greater than or equal to 18 years at the time of signing the informed consent
    form.

    3. Must be able to adhere to the study visit schedule and other protocol requirements.

    4. Must have a documented diagnosis of B-cell CLL (IWCLL guidelines for the diagnosis
    and treatment of chronic lymphocytic leukemia [Hallek, 2008]).

    5. Must have been treated with one of the following in first and/or second line:

    - a purine analog-containing regimen

    - a bendamustine-containing regimen

    - an anti-CD20 antibody-containing regimen

    - a chlorambucil-containing regimen

    - an alemtuzumab-containing regimen (for those subjects with a 17p deletion)

    6. Must have achieved a minimum response of partial response (PR, nPR, CRi, CR, and
    MRD-negative CR) (IWCLL guidelines for the diagnosis and treatment of chronic
    lymphocytic leukemia [Hallek, 2008]) following completion of second-line induction
    therapy prior to randomization (documentation of response status must be available).
    Second-line induction therapy must be documented to have been of sufficient duration.

    7. Must have completed last cycle of second-line induction no less than 8 weeks (56
    days) and no greater than 20 weeks (140 days) prior to randomization.

    8. Must have an ECOG performance status score of less than or equal to 2.

    9. Females of childbearing potential (FCBP) must:

    - Have two negative medically supervised pregnancy tests prior to starting of
    study therapy. She must agree to ongoing pregnancy testing during the course of
    the study, and after end of study therapy. This applies even if the subject
    practices complete and continued sexual abstinence.

    - Either commit to continued abstinence from heterosexual contact (which must be
    reviewed on a monthly basis) or agree to use, and be able to comply with,
    effective contraception without interruption, 28 days prior to starting study
    drug, during the study therapy (including dose interruptions), and for 28 days
    after discontinuation of study therapy.

    10. Male subjects must:

    - Commit to continued abstinence from heterosexual contact or agree to use a
    condom during sexual contact with a FCBP, even if they have had a vasectomy,
    throughout study drug therapy, during any dose interruption and after cessation
    of study therapy.

    - Agree to not donate semen during study drug therapy and for a period after end
    of study drug therapy.

    11. All subjects must:

    - Have an understanding that the study drug could have a potential teratogenic
    risk.

    - Agree to abstain from donating blood while taking study drug therapy and
    following discontinuation of study drug therapy. Agree not to share study
    medication with another person.

    - All subjects must be counseled about pregnancy precautions and risks of fetal
    exposure.

    Exclusion Criteria:

    1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
    would prevent the subject from participating in the study.

    2. Active infections requiring systemic antibiotics.

    3. Systemic infection that has not resolved > 2 months prior to initiating lenalidomide
    treatment in spite of adequate anti-infective therapy

    4. Autologous or allogeneic bone marrow transplant as second-line therapy.

    5. Pregnant or lactating females.

    6. Systemic treatment for B-cell CLL in the interval between completing the last cycle
    of second-line induction therapy and randomization.

    7. Participation in any clinical study or having taken any investigational therapy for a
    disease other than CLL within 28 days prior to initiating maintenance therapy.

    8. Known presence of alcohol and/or drug abuse.

    9. Central nervous system involvement as documented by spinal fluid cytology or imaging.
    Subjects who have signs or symptoms suggestive of leukemic meningitis or a history
    of leukemic meningitis must have a lumbar puncture procedure performed within two
    weeks prior to randomization.

    10. Prior history of malignancies, other than CLL, unless the subject has been free of
    the disease for 5 years. Exceptions include the following:

    - Basal cell carcinoma of the skin

    - Squamous cell carcinoma of the skin

    - Carcinoma in situ of the cervix

    - Carcinoma in situ of the breast

    - Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

    11. History of renal failure requiring dialysis.

    12. Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), and/or
    active Hepatitis C Virus (HCV) infection.

    13. Prior therapy with lenalidomide.

    14. Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be
    enrolled upon correction of electrolyte abnormalities).

    15. Any of the following laboratory abnormalities:

    - Calculated (method of Cockroft-Gault) creatinine clearance <60 mL/min.

    - Absolute neutrophil count (ANC) <1,000/L (1.0 X 109/L)

    - Platelet count <50,000/L (50 X 109/L)

    - Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase
    (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase
    (SGPT) > 3.0 x upper limit of normal (ULN)

    - Serum total bilirubin >2.0 mg/dL (with the exception of Gilbert's Syndrome)

    16. Grade 4 rash due to prior thalidomide treatment

    17. Uncontrolled hyperthyroidism or hypothyroidism

    18. Venous thromboembolism within one year

    19. Greater than or equal to Grade-2 neuropathy

    20. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

    21. Disease transformation (active) (ie, Richter's Syndrome, prolymphocytic leukemia)

    22. Known allergy to allopurinol for subjects assessed with PR following their
    second-line induction therapy.

    23. Prisoners.

    24. More than 2 prior lines of CLL therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Survival

    240 Events For Progression Free Survival

    Secondary Outcome Measures

    The number, type, frequency and severity of adverse events (AEs)

    Tumor Response

    Duration of Response

    Health Related Quality of Life-Fact Leukemia Survey Version 4.0

    Health Related Quality of Life EQ5-D

    Trial Keywords