Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)
The purpose of this study is to determine the safety and efficacy of lenalidomide as a first line therapy in treating patients with B-cell Chronic Lymphocytic Leukemia. This study will compare the effects (good and bad) of lenalidomide with chlorambucil.
B-Cell Chronic Lymphocytic Leukemia (B-CLL)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL, PARALLEL-GROUP STUDY OF THE EFFICACY AND SAFETY OF LENALIDOMIDE (REVLIMID®) VERSUS CHLORAMBUCIL AS FIRST-LINE THERAPY FOR PREVIOUSLY UNTREATED ELDERLY PATIENTS WITH B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA|
- Progression Free Survival (PFS) [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]Number of participants who survive without progressing
- Safety [type, frequency, and severity of adverse events (AEs)] [ Time Frame: Up to 105 months; every 28 days ] [ Designated as safety issue: Yes ]An adverse event (AE) is any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a patient during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairmentof the patient'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 thatmedical condition, this should be considered an AE.
- Overall Survival [ Time Frame: Up to 105 months ] [ Designated as safety issue: No ]Overall Survival is defined as the time between randomization and death
- Number of anti-cancer therapies obtained from randomized participants [ Time Frame: Up to 105 months ] [ Designated as safety issue: No ]Anti-cancer therapies administered to all randomized study participants during the follow up period
- Response, including evaluation of minimal residual disease (MRD) by flow cytometry (Hallek, 2008) [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]Response, including evaluation of minimal residual disease (MRD), will be assessed by IWCLL guidelines for diagnosis and treatment of CLL. The response rate based on the best response during the treatment period and the relative proportions in each response category will be examined.
- Duration of response [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]Duration of response is defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression and is determined
- Time to response [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]Time to response is calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines
- Health-Related Quality of Life (HRQL) by Functional Assessment of Cancer Therapy -Leukemia (FACT-Leu) and EQ-5D [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]FACT-Leukemia is a validated cancer quality of life measure used to evaluate patients receiving cancer treatment.
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Experimental: 1 - Lenalidomide
1 - Lenalidomide
For patients with normal renal function (defined as CrCl ≥ 60 mL/min), 5 mg once daily on Days 1 through 28 of the first 28-day cycle, 10 mg once daily on Days 1 through 28 starting at the second cycle, 15 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.
For patients with moderate renal impairment (defined as CrCl ≥ 30 to < 60 mL/min), 2.5 mg once daily on Days 1 through 28 of the first 28-day cycle, 5 mg once daily on Days 1 through 28 starting at the second cycle, 7.5 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.
Other Name: Revlimid
Active Comparator: 2- Chlorambucil
Patients assigned to the chlorambucil arm will receive oral chlorambucil tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Other Name: Leukeran
After notification from the US Food and Drug Administration (FDA) on 12 July 2013, Celgene agreed to discontinue the lenalidomide treatment for all patients due to an imbalance in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil. No specific causality for this imbalance has been identified to date. Investigators were instructed to immediately discontinue all participants from experimental lenalidomide treatment and inform their patients accordingly. Participants on the Chlorambucil arm may continue up to 12 months (13 cycles) with the last participant completing in March 2014. All randomized participants will continue to be followed for overall survival and secondary primary malignancies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00910910
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|Study Director:||Oliver Kong, MD||Celgene Corporation|