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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00774345
Recruitment Status : Active, not recruiting
First Posted : October 17, 2008
Last Update Posted : December 13, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE October 16, 2008
First Posted Date  ICMJE October 17, 2008
Last Update Posted Date December 13, 2019
Actual Study Start Date  ICMJE January 27, 2009
Estimated Primary Completion Date October 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2014)
  • Overall Survival [ Time Frame: 8 years ]
    Overall survival is defined as the time from randomization to death of any cause
  • 240 Events For Progression Free Survival [ Time Frame: 6 years ]
    Progression free survival (PFS) is defined as the time from randomization to disease progression or death due to any cause during or after the treatment period, whichever comes first
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2008)
  • Overall Survival [ Time Frame: After 340 events have occured ]
  • Progression Free Survival [ Time Frame: After 340 events have occured ]
Change History Complete list of historical versions of study NCT00774345 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2014)
  • The number, type, frequency and severity of adverse events (AEs) [ Time Frame: Up to 8 years; All AEs will be recorded by the Investigator(s) from the time of signing of informed consent ]
    An adverse event (AE) is any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values (as specified by the criteria below), regardless of etiology. Any medical condition that was present prior to study treatment and that remains unchanged or improved should not be recorded as an AE. If there is a worsening of that medical condition, this should be considered an AE.
  • Tumor Response [ Time Frame: 6 years ]
    Tumor response is defined as the patient's best response to treatment as defined by the iwCLL guidelines.
  • Duration of Response [ Time Frame: 6 years ]
    Duration of response is defined as the time from first evaluation of an improved response from the patient's baseline condition until progression of disease.
  • Health Related Quality of Life-Fact Leukemia Survey Version 4.0 [ Time Frame: 6 years ]
    The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease.
  • Health Related Quality of Life EQ5-D [ Time Frame: 6 years ]
    The standardized extended version of EQ-5D was designed for the collection of health state. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
Brief 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.
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE B-cell Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • Drug: Lenalidomide
    Lenalidomide capsules given orally on days 1-28 of a 28 day cycle
    Other Name: Revlimid
  • Drug: Placebo
    Placebo capsules given orally on days 1 - 28 of a 28 day cycle
Study Arms  ICMJE
  • Experimental: 1
    Lenalidomide po qd on days 1-28 of a 28 day cycle
    Intervention: Drug: Lenalidomide
  • Placebo Comparator: 2
    Placebo capsules given orally on days 1-28 of a 28 day cycle
    Intervention: Drug: Placebo
Publications * Chanan-Khan AA, Zaritskey A, Egyed M, Vokurka S, Semochkin S, Schuh A, Kassis J, Simpson D, Zhang J, Purse B, Foà R. Lenalidomide maintenance therapy in previously treated chronic lymphocytic leukaemia (CONTINUUM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2017 Nov;4(11):e534-e543. doi: 10.1016/S2352-3026(17)30168-0. Epub 2017 Sep 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 30, 2015)
317
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2008)
680
Estimated Study Completion Date  ICMJE October 27, 2020
Estimated Primary Completion Date October 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Colombia,   Czechia,   Denmark,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Mexico,   Netherlands,   New Zealand,   Poland,   Portugal,   Romania,   Russian Federation,   South Africa,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00774345
Other Study ID Numbers  ICMJE CC-5013-CLL-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Richard Delarue, MD Celgene Corporation
PRS Account Celgene
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP