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
Condition: B-cell Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Lenalidomide; Placebo
Intervention description: Lenalidomide capsules given orally on days 1-28 of a 28 day cycle; Placebo capsules given orally on days 1 - 28 of a 28 day cycle
Intervention MeSH terms: Lenalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 317.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

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/μL (1.0 X 109/L)

               -  Platelet count <50,000/μL (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.