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Fludarabine and Cyclophosphamide With or Without Rituximab in Patients With Previously Untreated Chronic B-Cell Lymphocytic Leukemia (CLL-8)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00281918
First Posted: January 25, 2006
Last Update Posted: September 19, 2013
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.
Collaborator:
German CLL Study Group
Information provided by (Responsible Party):
Hoffmann-La Roche
Results First Submitted: December 21, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Leukemia
Interventions: Drug: Rituximab
Drug: Cyclophosphamide
Drug: Fludarabine Phosphate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

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
Fludarabine+Cyclophosphamide (FC) Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
Fludarabine+Cyclophosphamide+Rituximab (FCR) Rituximab intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: 375 mg/m² IV on Day 0; Cycles 2-6: 500 mg/m² IV on Day 1. FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV over 15-30 min on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV over 15-30 min on Days 1, 2, 3 for 6 cycles.

Participant Flow:   Overall Study
    Fludarabine+Cyclophosphamide (FC)   Fludarabine+Cyclophosphamide+Rituximab (FCR)
STARTED   409 [1]   408 [2] 
Safety Population; Received Study Drug   398   402 
COMPLETED   267 [3]   300 [3] 
NOT COMPLETED   142   108 
[1] Informed consent unavailable for 2 patients at time of analysis; intent-to-treat population was 407.
[2] Informed consent unavailable for 5 patients at time of analysis; intent-to-treat population was 403.
[3] Completed all 6 cycles of study medication.



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Fludarabine+Cyclophosphamide (FC) Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
Fludarabine+Cyclophosphamide+Rituximab (FCR) Rituximab intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: 375 mg/m² IV on Day 0; Cycles 2-6: 500 mg/m² IV on Day 1. FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV over 15-30 min on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV over 15-30 min on Days 1, 2, 3 for 6 cycles.
Total Total of all reporting groups

Baseline Measures
   Fludarabine+Cyclophosphamide (FC)   Fludarabine+Cyclophosphamide+Rituximab (FCR)   Total 
Overall Participants Analyzed 
[Units: Participants]
 407   403   810 
Age 
[Units: Years]
Mean (Standard Deviation)
 59.3  (8.55)   59.6  (8.70)   59.5  (8.62) 
Gender 
[Units: Participants]
     
Female   105   105   210 
Male   302   298   600 


  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS)   [ Time Frame: Median observation time at time of analysis was approximately 21 months ]

2.  Primary:   Final Analysis: Time to Progression-free Survival Event   [ Time Frame: Median observation time was approximately 66.4 months ]

3.  Secondary:   Event-free Survival (EFS)   [ Time Frame: Median observation time at time of analysis was approximately 21 months ]

4.  Secondary:   Overall Survival (OS)   [ Time Frame: Median observation time at time of analysis was approximately 21 months ]

5.  Secondary:   Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).   [ Time Frame: Median observation time at time of analysis was approximately 21 months ]

6.  Secondary:   Final Analysis: Time to Overall Survival Event   [ Time Frame: Median observation time was approximately 66.4 months ]

7.  Secondary:   Final Analysis: Time to Event-free Survival Event   [ Time Frame: Median observation time was approximately 66.4 months ]

8.  Secondary:   Final Analysis: Time to Disease-free Survival (DFS) Event in Participants With Complete Response (CR)   [ Time Frame: Median observation time was approximately 66.4 months ]

9.  Secondary:   Final Analysis: Duration of Response   [ Time Frame: Median observation time was approximately 66.4 months ]
  Hide Outcome Measure 9

Measure Type Secondary
Measure Title Final Analysis: Duration of Response
Measure Description Duration of response was defined as the time from the first documented Complete Response, Partial Response to disease progression or death by any cause.
Time Frame Median observation time was approximately 66.4 months  

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.
Participants from the Intent-to-treat population, all randomized participants, with complete response or partial response who experienced an event (disease progression or death due to any cause).

Reporting Groups
  Description
Fludarabine+Cyclophosphamide (FC) Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
Fludarabine+Cyclophosphamide+Rituximab (FCR) Rituximab intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: 375 mg/m² IV on Day 0; Cycles 2-6: 500 mg/m² IV on Day 1. FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV over 15-30 min on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV over 15-30 min on Days 1, 2, 3 for 6 cycles.

Measured Values
   Fludarabine+Cyclophosphamide (FC)   Fludarabine+Cyclophosphamide+Rituximab (FCR) 
Participants Analyzed 
[Units: Participants]
 214   207 
Final Analysis: Duration of Response 
[Units: Days]
Median (95% Confidence Interval)
 1102.0 
 (977 to 1249) 
 1718.0 
 (1618 to 1859) 


Statistical Analysis 1 for Final Analysis: Duration of Response
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] <.0001
Hazard Ratio (HR) [5] 0.58
95% Confidence Interval 0.48 to 0.71
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[5] Other relevant estimation information:
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10.  Secondary:   Final Analysis: Percentage of Participants With Complete Response (CR) and Partial Response   [ Time Frame: Median observation time was approximately 66.4 months ]

11.  Secondary:   Final Analysis: Time to New Treatment for Chronic Lymphocytic Leukemia(CLL)   [ Time Frame: Median observation time was approximately 66.4 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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: Medical Communications
Organization: Hoffmann-LaRoche
phone: 800-821-8590


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00281918     History of Changes
Other Study ID Numbers: CDR0000454560
GCLLSG-CLL-8
EU-20560
ML17102
First Submitted: January 24, 2006
First Posted: January 25, 2006
Results First Submitted: December 21, 2009
Results First Posted: March 29, 2011
Last Update Posted: September 19, 2013