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.
Subjects currently on lenalidomide treatment will discontinue lenalidomide treatment
immediately and complete the Treatment Discontinuation assessment. The subjects will then
transition to the survival follow-up period.
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.
