Relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) who have achieved at least partial response (PR) to second-line therapy. MedDRA version: 21.1 Level: LLT Classification code 10008978 Term: Chronic lymphocytic leukemia refractory System Organ Class: 100000004864
Conditions
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must understand and voluntarily sign an informed consent form. 2. Age = 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 -or 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] Appendix 22.4) 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 Eastern Cooperative Oncology Group (ECOG) performance status score of =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. Abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]. 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. Abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]. • 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 137 F.1.3 Elderly
Exclusion criteria
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 (CNS) 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 of 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. = Grade-2 neuropathy 20. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia 21. Disease transformation (active) (i.e. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of lenalidomide versus placebo maintenance therapy;Secondary Objective: To evaluate the safety of lenalidomide versus placebo maintenance therapy;Primary end point(s): • Overall Survival (OS) ;Timepoint(s) of evaluation of this end point: Overall Survival [ Time Frame: 8 years ] | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Progression Free Survival 2 (PFS2) ;Timepoint(s) of evaluation of this end point: Safety: ongoing PFS: Time frame 6 years | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed