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
Verified April 2014 by Celgene Corporation
Information provided by (Responsible Party):
First received: October 16, 2008
Last updated: April 23, 2014
Last verified: April 2014
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.
B-cell Chronic Lymphocytic Leukemia
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Efficacy and Safety of Lenalidomide (Revlimid®) as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia Following Second Line Therapy (THE CONTINUUM TRIAL)
Primary Outcome Measures:
- Overall Survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]
- 240 Events For Progression Free Survival [ Time Frame: 6 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Safety [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]
- Tumor Response [ Time Frame: 6 years ] [ Designated as safety issue: No ]
- Duration of Response [ Time Frame: 6 years ] [ Designated as safety issue: No ]
- Health Related Quality of Life [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2018 (Final data collection date for primary outcome measure)
Lenalidomide po qd on days 1-28 of a 28 day cycle
Lenalidomide capsules given orally on days 1-28 of a 28 day cycle
Other Name: Revlimid
Placebo Comparator: 2
Placebo 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
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Must understand and voluntarily sign an informed consent form.
- Must be greater than or equal to 18 years at the time of signing the informed consent form.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Must have a documented diagnosis of B-cell CLL (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008]).
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)
- 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.
- 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.
- Must have an ECOG performance status score of less than or equal to 2.
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.
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.
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.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Active infections requiring systemic antibiotics.
- Systemic infection that has not resolved > 2 months prior to initiating lenalidomide treatment in spite of adequate anti-infective therapy
- Autologous or allogeneic bone marrow transplant as second-line therapy.
- Pregnant or lactating females.
- Systemic treatment for B-cell CLL in the interval between completing the last cycle of second-line induction therapy and randomization.
- 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.
- Known presence of alcohol and/or drug abuse.
- 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.
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)
- History of renal failure requiring dialysis.
- Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), and/or active Hepatitis C Virus (HCV) infection.
- Prior therapy with lenalidomide.
- Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
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)
- Grade 4 rash due to prior thalidomide treatment
- Uncontrolled hyperthyroidism or hypothyroidism
- Venous thromboembolism within one year
- Greather than or equal to Grade-2 neuropathy
- Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
- Disease transformation (active) (ie, Richter's Syndrome, prolymphocytic leukemia)
- Known allergy to allopurinol for subjects assessed with PR following their second-line induction therapy.
- More than 2 prior lines of CLL therapy.
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: NCT00774345
||Oliver Kong, MD
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 16, 2008
||April 23, 2014
||United States: Food and Drug Administration
Canada: Health Canada
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Ministry of Health
South Africa: Medicines Control Council
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 26, 2014
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Immune System Diseases
Physiological Effects of Drugs
Angiogenesis Modulating Agents