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Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial) (ORIGIN)

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ClinicalTrials.gov Identifier: NCT00910910
Recruitment Status : Active, not recruiting
First Posted : June 1, 2009
Results First Posted : December 21, 2016
Last Update Posted : October 2, 2017
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: B-Cell Chronic Lymphocytic Leukemia
Interventions: Drug: Lenalidomide
Drug: Chlorambucil

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
After notification by the US Food and Drug Administration on 12/Jul/2013, Celgene agreed to stop lenalidomide due to an imbalance in the number of deaths on the lenalidomide arm versus the chlorambucil arm; no causality for the imbalance was identified; the investigators stopped the lenalidomide; patients on chlorambucil could take up to 13 cycles.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Lenalidomide For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil Chlorambucil oral 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).

Participant Flow:   Overall Study
    Lenalidomide   Chlorambucil
STARTED   225   225 
Safety Population   224 [1]   223 [1] 
COMPLETED   0 [2]   1 [2] 
NOT COMPLETED   225   224 
Adverse Event                63                35 
PD without histologic change                27                23 
PD with histologic change                0                2 
Withdrawal by Subject                7                5 
Lost to Follow-up                2                2 
Death                9                3 
Protocol Violation                2                2 
Completed 13 cycles of treatment                0                118 
Other                114                32 
Untreated before cycle 1                1                2 
[1] All randomized participants who received at least 1 dose of the either lenalidomide or chlorambucil
[2] Completed includes participants who are continuing with ongoing treatment



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.

Reporting Groups
  Description
Lenalidomide For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil Chlorambucil oral 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).
Total Total of all reporting groups

Baseline Measures
   Lenalidomide   Chlorambucil   Total 
Overall Participants Analyzed 
[Units: Participants]
 225   225   450 
Age 
[Units: Years]
Mean (Standard Deviation)
 73.0  (5.72)   73.3  (5.72)   73.1  (5.72) 
Sex: Female, Male [1] 
[Units: Participants]
Count of Participants
     
Female      93  41.3%      83  36.9%      176  39.1% 
Male      132  58.7%      142  63.1%      274  60.9% 
[1] The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.


  Outcome Measures

1.  Primary:   Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off of 31 March 2014   [ Time Frame: Data cut-off of 31 March 2014; up to approximately 53 months ]

2.  Primary:   Kaplan-Meier Estimate of Progression Free Survival (PFS)   [ Time Frame: Data cut-off of 18 Feb 2013; up to approximately 39 months ]

3.  Secondary:   Number of Participants With Adverse Events (AEs)   [ Time Frame: From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil ]

4.  Secondary:   Number of Participants With Adverse Events (AEs) With a Later Cut-off of 31 March 2014   [ Time Frame: From randomization to the data cut-off of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil ]

5.  Secondary:   Kaplan-Meier Estimate for Duration of Response With a Later Cut-off of 31 March 2014   [ Time Frame: Up to data cut-off of 31 March 2014; up to approximately 53 months ]

6.  Secondary:   Time to Response for a Later Cut-off of 31 March 2014   [ Time Frame: Up to data cut-off of 31 March 2014; up to approximately 53 months ]

7.  Secondary:   Kaplan Meier Estimate for Overall Survival   [ Time Frame: Up to data cut off of 18 Feb 2013; up to approximately 39 months; ]

8.  Secondary:   Kaplan Meier Estimate of Overall Survival for a Later Cut-off of 31 March 2014   [ Time Frame: Up to data cut off of 31 March 2014; up to approximately 53 months; median follow-up was 18.8 months ]

9.  Secondary:   Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument   [ Time Frame: Day 1 and once every 8 weeks ]

10.  Secondary:   Euro Quality of Life Five Dimension (EQ-5D) Questionnaire   [ Time Frame: Day 1 and once every 8 weeks ]

11.  Secondary:   Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia Guidelines (IWCLL) Guidelines   [ Time Frame: Up to data cut-off of 18 Feb 2013; approximately 39 months ]

12.  Secondary:   Percentage of Participants With Overall Response Based on IWCLL Guidelines With a Later Cut-off of 31 March 2014   [ Time Frame: Up to data cut-off of 31 March 2014; approximately 53 months ]

13.  Secondary:   Kaplan-Meier Estimate for Duration of Response   [ Time Frame: Up to data cut-off of 18 Feb 2013; up to approximately 39 months ]

14.  Secondary:   Time to Response   [ Time Frame: Up to data cut-off of 18 Feb 2013; up to approximately 39 months ]

15.  Secondary:   Number of Participants With Subsequent Anti-cancer Therapies Received Post Treatment   [ Time Frame: Up to data cut-off of 31 March 2014; up to approximately 53 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain, Senior Manager of Clinical Trial Disclosure
Organization: Celgene Corporation
phone: 888-260-1599
e-mail: ClinicalTrialDisclosure@Celgene.com



Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT00910910     History of Changes
Other Study ID Numbers: CC-5013-CLL-008
2008-003079-32 ( EudraCT Number )
First Submitted: May 28, 2009
First Posted: June 1, 2009
Results First Submitted: September 23, 2015
Results First Posted: December 21, 2016
Last Update Posted: October 2, 2017