Patients with Chronic Lymphocytic Leukemia Binet A stage.
Conditions
Interventions
Trade Name: Imbruvica
Product Name: Ibrutinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
Other descriptive name: IBRUTINIB
Concentration unit: mg milligram(s)
Concentration type
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion-Criteria: • Confirmed diagnosis of previously untreated CLL according to the updated iwCLL guidelines • Stage Binet A without need for treatment • Age = 18 years • Life expectancy = 6 months • ECOG performance status 0 – 2 • Absolute neutrophil count (ANC = 1 x 109 / L) • Signed written informed consent of patient and treating physician Females of childbearing potential (FCBP)† in the experimental treatment arm (placebo / ibrutinib) must: • Have one negative medically supervised pregnancy test prior to starting the study therapy. • Either commit to continued abstinence from heterosexual intercourse or agree to use, and be able to comply with, two reliable forms of effective contraception simultaneously to achieve a PEARL-Index =65 years) yes F.1.3.1 Number of subjects for this age range 324
Exclusion criteria
Exclusion criteria: Exclusion-Criteria: • Any prior CLL specific therapy • Recent therapeutic interventions including: - All other chemotherapy, radiation therapy within 3 weeks prior to randomization - Any surgery within 4 weeks prior to randomization • Prior treatment with Ibrutinib or BTK inhibitors • Chronic use of steroids in excess of prednisone 20mg/day or its equivalent • Active infections requiring systemic antibiotics • An life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion could compromise the subject’s safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk • Pregnant or lactating females • 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 • Known second malignancy that limits survival to less than two years • Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) and/or active Hepatitis C Virus (HCV) infection. • Any of the following laboratory abnormalities: a. Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 2.5 x upper limit of normal (ULN) b. Serum total bilirubin > 1.5 ULN (with the exception of Gilbert’s Syndrome) c. Creatinine clearance < 30ml/min • Requires anticoagulant with warfarin or phenoprocoumon • Requires anticoagulant with oral direct Xa inhibitors (rivaroxaban, apixaban, edoxaban) • History of stroke or intracranial hemorrhage within 6 months prior to randomization • Requires treatment with strong CYP3A4/5 inhibitors (see section 8.6.3) • Participation in any clinical study for CLL or having taken any investigational therapy which would interfere with the study drug for a disease other than CLL within 28 days prior to initiating treatment. • Prisoners or subjects who are institutionalized by regulatory or court order or persons who are in dependence to the sponsor or an investigator • Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate superiority of ibrutinib over placebo in prolonging EFS for subjects with treatment-naïve CLL stage A and intermediate or (very) high risk of disease progression. All subjects with intermediate, (very) high risk randomized to the experimental treatment arm will be treated up to active progressive disease with treatment indication according to iwCLL-Guidelines with the objective to demonstrate prolongation of EFS for the ibrutinib arm. EFS is defined as the time between randomization until active progressive disease with treatment indication according to the iwCLL-Guidelines with subsequent treatment for CLL or death. ;Secondary Objective: The secondary objectives are: •To demonstrate superiority of ibrutinib over placebo in prolonging overall survival (OS) for subjects with treatment-naïve CLL stage A and intermediate or (very) high risk of disease Progression •To evaluate the safety of ibrutinib versus placebo ;Primary end point(s): Primary study endpoint: •EFS based on an internal medical review according to iwCLL guidelines ;Timepoint(s) of evaluation of this end point: The primary endpoint analysis for EFS will be conducted as soon as 71 EFS events have been documented for patients from the study arms II and III. Based on the current recruitment and observed event pattern this time point will likely be reached at the end of recruitment or closely thereafter (month 52 after FPI or later). Nonetheless, recruitment must be finished at the time of analysis. If the event number will be reached before, the analysis will be shifted to the end of recruitment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints for treatment arms: - OS defined by the time between randomization and death due to any cause - Progression-free survival (PFS) - Treatment-free survival (TFS) - Type, response and duration of response to subsequent treatment for CLL - Safety (excluding second primary malignancies) - Assessment of medication-taking behavior (compliance to study mediacation) Secondary endpoints for all study arms - Overall survival (OS) - Other toxicities - Health quality and health outcome - exploratory endpoints Secondary endpoints for study arm I (watch&wait cohort) - OS defined by the time between completed registration and death due to any cause - Event-free survival - Time to first CLL treatment;Timepoint(s) of evaluation of this end point: The secondary endpoint OS will be analyzed two years after the end of recruitment (approximately month 76) for the first time within one formal interim analysis for assessing both efficacy and futility (including non-binding boundaries). The final OS analysis will be conducted either as soon as 46 OS events have been observed or at the end of the study (90 months after randomization of the first subject). At this time-point, other secondary endpoints will be fully analyzed based on all patients from study arms I, II and III. | — |
Countries
Germany
Contacts
Public ContactGerman CLL Study Group
University Hospital of Cologne
Outcome results
None listed