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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:
Collaborator:
German CLL Study Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00281918
First received: January 24, 2006
Last updated: September 9, 2013
Last verified: September 2013
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
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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.

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.
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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 
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 ]

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
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Time Frame Adverse Events were recorded until 28 days after completion of study treatment (median time approximately 21 months). Serious Adverse Events reported until 1 year post-treatment or initiation of new CLL treatment (median time approximately 42 months).
Additional Description The safety population included all participants who received at least one dose of study drug.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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.

Other Adverse Events
    Fludarabine+Cyclophosphamide (FC)   Fludarabine+Cyclophosphamide+Rituximab (FCR)
Total, other (not including serious) adverse events     
# participants affected / at risk   122/398 (30.65%)   185/402 (46.02%) 
Blood and lymphatic system disorders     
Neutropenia † 1     
# participants affected / at risk   71/398 (17.84%)   116/402 (28.86%) 
Leukopenia † 1     
# participants affected / at risk   45/398 (11.31%)   88/402 (21.89%) 
Thrombocytopenia † 1     
# participants affected / at risk   35/398 (8.79%)   21/402 (5.22%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (15.0)



  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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