Ibrutinib in Previously Untreated Binet Stage A Chronic Lymphocytic Leukemia With Risk of Disease Progression (CLL12)
|ClinicalTrials.gov Identifier: NCT02863718|
Recruitment Status : Active, not recruiting
First Posted : August 11, 2016
Last Update Posted : June 11, 2020
This is a prospective, multicenter, randomized, placebo-controlled, double-blind phase III study that compares the efficacy and safety of oral ibrutinib in previously untreated Binet stage A CLL patients without treatment indication according to iwCLL guidelines but risk of early disease progression.
For event-free survival (EFS), an improvement from 24 months for untreated intermediate or (very) high risk CLL to 48 months for subjects treated with ibrutinib is considered clinically relevant. Ibrutinib / placebo is administered continuously orally until symptomatic disease progression, unacceptable toxicity, or voluntary treatment withdrawal, whichever occurs first.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: Ibrutinib Drug: Placebo||Phase 3|
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.
The secondary objectives are:
- To evaluate the prolongation of overall survival of ibrutinib versus placebo
- To evaluate the safety of ibrutinib versus placebo
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||515 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Placebo-Controlled, Double-Blind, Randomized, Multicenter, Three Arm Phase III Trial to Compare the Efficacy and Safety of Ibrutinib vs. Placebo in Previously Untreated Binet Stage A Chronic Lymphocytic Leukemia Patients With Risk of Early Disease Progression|
|Actual Study Start Date :||April 30, 2014|
|Actual Primary Completion Date :||March 7, 2019|
|Estimated Study Completion Date :||April 2022|
No Intervention: Watch & wait
Watch & wait
Placebo Comparator: Placebo 420 mg/d
Placebo 420mg daily
Active Comparator: Ibrutinib 420mg/d
Bruton's tyrosine kinase Inhibitor Ibrutinib 420mg daily
Other Name: Imbruvica
- Event-free survival (EFS) [ Time Frame: randomization until progression, initiation of subsequent treatment for CLL or death by any cause, whichever occurs first, assessed for at at least 60 months ]EFS is defined as the time between the date of completed registration and time point of symptomatic disease progression with treatment indication, initiation of subsequent treatment for CLL or death by any cause, whichever occurs first. These will be counted as event for EFS.
- Treatment-free survival [ Time Frame: time of randomization until the date of initiation of subsequent treatment for CLL or death by any cause assessed for at at least 60 months ]The primary efficacy parameter is event-free survival (EFS) defined as the time of randomization until symptomatic disease progression with treatment indication, initiation of subsequent treatment for CLL or death by any cause, whichever occurs first
- Progression-free survival (PFS) [ Time Frame: the time of randomization until symptomatic disease progression (as defined by the updated iwCLL-guidelines) or death by any cause, whichever occurs first, assessed for at at least 60 months ]PFS is defined by the time of randomization until symptomatic disease progression (as defined by the updated iwCLL-guidelines) or death by any cause, whichever occurs first. These will be counted as event for PFS. Patients for whom no documented event for PFS is available at the time of analysis will be censored at the time point of last follow-up information they were assessed to be event-free.
- Response rates (Overall response rate (ORR); Complete Remission (CR); Partial Remission (PR) [ Time Frame: Overall response rate (ORR) achieved during treatment or within 6 months of end of treatment, complete response (CR) and partial response (PR) rates will be evaluated for at least 60 months or Progression whichever occurs first ]ORR, CR- and PR- rates are defined by the proportion of patients having achieved a response (CR/CRi and nPR/PR), CR/CRi and nPR/PR as best response respectively based on the respective population.
- rate of Treatment-related adverse events [ Time Frame: randomization until 28 days after the last dose of study drug ]
- Overall survival (OS) [ Time Frame: date of randomization to the date of death for at least 60 months ]
Respectively, for watch & wait- patients (study arm I) the date of completed registration will be used. Additionally, OS will also be calculated for the time period between first diagnosis of CLL and death due to any cause. Subjects who have not yet died at the time of analysis will be censored at the time of last follow-up information they were assessed to be alive.
The exact cause of death will be recorded, with additional differentiation between CLL-related, treatment-related and other causes.
Furthermore overall survival will be analyzed using a multivariate Cox regression model adjusted for risk category, study arm, and baseline prognostic factors
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02863718
|German CLL Study Group|
|Cologne, Germany, 50935|
|Principal Investigator:||Petra Langerbeins, MD||German CLL Study Group|