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A Study to Assess the Effect of Maintenance Treatment With Rituximab Versus No Treatment in Participants With Progressive B-Cell Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT00718549
Recruitment Status : Completed
First Posted : July 18, 2008
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Lymphocytic Leukemia, Chronic
Interventions: Drug: Cladribine
Drug: Cyclophosphamide
Drug: Rituximab

  Participant Flow

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
A total 136 participants were screened, out of which 128 participants were enrolled in this study.

Reporting Groups
  Description
Induction: Rituximab, Cladribine, Cyclophosphamide Participants received rituximab at a dose of 375 milligrams per meter squared (mg/m^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 minutes (min) on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.
Maintenance Arm: Rituximab Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Observation Arm: No Intervention Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.

Participant Flow for 2 periods

Period 1:   Induction Phase
    Induction: Rituximab, Cladribine, Cyclophosphamide   Maintenance Arm: Rituximab   Observation Arm: No Intervention
STARTED   128   0   0 
COMPLETED   66   0   0 
NOT COMPLETED   62   0   0 
Disease Progression                1                0                0 
Eligibility Criteria Violation                2                0                0 
Early Termination - No Additional Info                59                0                0 

Period 2:   Maintenance/ Observation Phase
    Induction: Rituximab, Cladribine, Cyclophosphamide   Maintenance Arm: Rituximab   Observation Arm: No Intervention
STARTED   0   33   33 
COMPLETED   0   5   3 
NOT COMPLETED   0   28   30 
Early Termination - No Additional Info                0                15                8 
Death                0                1                2 
Lost to Follow-up                0                4                4 
Progression                0                5                14 
Relapse                0                3                2 



  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.
All enrolled participants who received at least one dose of study medication.

Reporting Groups
  Description
Induction: Rituximab, Cladribine, Cyclophosphamide Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.

Baseline Measures
   Induction: Rituximab, Cladribine, Cyclophosphamide 
Overall Participants Analyzed 
[Units: Participants]
 128 
Age 
[Units: Years]
Mean (Standard Deviation)
 57.5  (8.3) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      44  34.4% 
Male      84  65.6% 


  Outcome Measures

1.  Primary:   Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)   [ Time Frame: From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years) ]

2.  Primary:   Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL   [ Time Frame: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years) ]

3.  Secondary:   Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL   [ Time Frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129) ]

4.  Secondary:   Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR   [ Time Frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129) ]

5.  Secondary:   PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors   [ Time Frame: From randomization to PD, relapse, or death due to any cause (overall approximately 5 years) ]

6.  Secondary:   Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29   [ Time Frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29) ]

7.  Secondary:   Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129   [ Time Frame: 12 weeks after the end of maintenance treatment or observation phase (Week 129) ]

8.  Secondary:   Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29   [ Time Frame: 8 weeks after the last dose of rituximab during induction treatment (Week 29) ]

9.  Secondary:   Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129   [ Time Frame: 12 weeks after the end of maintenance treatment or observation phase (Week 129) ]


  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
In 2011 the recruitment was stopped due to low enrollment rate, and in 2015 the trial was prematurely discontinued.


  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: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00718549     History of Changes
Other Study ID Numbers: ML21283
2008-001140-39
First Submitted: July 16, 2008
First Posted: July 18, 2008
Results First Submitted: May 31, 2017
Results First Posted: August 20, 2018
Last Update Posted: August 20, 2018