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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 is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
German CLL Study Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00281918
First received: January 24, 2006
Last updated: November 20, 2012
Last verified: November 2012
History of Changes
Results First Received: December 21, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: 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
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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]
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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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  
Number of Participants  
[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 ]
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2.  Secondary:   Event-free Survival (EFS)   [ Time Frame: Median observation time at time of analysis was approximately 21 months ]
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3.  Secondary:   Overall Survival (OS)   [ Time Frame: Median observation time at time of analysis was approximately 21 months ]
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4.  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 ]
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Measure Type Secondary
Measure Title Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).
Measure Description CR is defined by at least 8 weeks of: 1)Absence of lymphadenopathy 2)No hepatomegaly or splenomegaly 3)Absence of B-symptoms 4)Normal blood count 5)Bone marrow aspirate and biopsy 8 weeks after the clinical and laboratory results demonstrated that a CR was achieved. A marrow sample had to be normocellular for age with less than 30% lymphocytes. Lymphoid nodules had to be absent. If marrow was hypocellular,a repeat biopsy was taken 4 weeks later and samples were re-reviewed in conjunction with the prior pathology. DFS was calculated from time of CR relapse or death. Median DFS was not reached.
Time Frame Median observation time at time of analysis was approximately 21 months  
Safety Issue No  

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 ITT population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not. Informed consent was unavailable at the time of analysis for 2 patients in the FC group and 5 patients in the FCR group. ITT population: FC = 407; FCR = 403.

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)  
Number of Participants Analyzed  
[units: participants]
 		  407     403  
Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).  
[units: Days to an event]
 		   
Minimum number of days to an event     84     91  
Maximum number of days to an event     1164     1226  


Statistical Analysis 1 for Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.7882
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] 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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  Serious Adverse Events
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  Other Adverse Events
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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.


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
These results are based on a clinical data cut-off date of 4 July 2007.  


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
phone: 800-821-8590


No publications provided by Hoffmann-La Roche

Publications automatically indexed to this study:


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00281918     History of Changes
Other Study ID Numbers: CDR0000454560, GCLLSG-CLL-8, EU-20560, ML17102
Study First Received: January 24, 2006
Results First Received: December 21, 2009
Last Updated: November 20, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices