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Trial record 16 of 91 for:    CLL [CONDITION] Lenalidomide [TREATMENT]

Study of Bendamustine/Rituxan Induction Chemotherapy With Revlimid Maintenance for Relapsed/Refractory CLL and SLL

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ClinicalTrials.gov Identifier: NCT00974233
Recruitment Status : Completed
First Posted : September 10, 2009
Results First Posted : July 13, 2017
Last Update Posted : July 13, 2017
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
University of Wisconsin, Madison

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions Drug: Bendamustine
Drug: Rituximab
Drug: Lenalidomide
Enrollment 34
Recruitment Details Research subjected from the University of Wisconsin and 7 Wisconsin Oncology Network institutions were enrolled from October 2009 to November 2011. Subjects were enrolled from outpatient hematology clinics at each participating institution.
Pre-assignment Details  
Arm/Group Title Induction Chemoimmunotherapy + Maintenance Lenalidomide
Hide Arm/Group Description Induction therapy: Bendamustine 90 mg/m2 IV on days 1 & 2 + rituximab 375 mg/m2 IV on day 1 (permitted on day 2 of cycle 1) every 28 days for total of 6 treatment cycles. Maintenance therapy: Lenalidomide 5-10 mg orally continuously of each 28-day cycles for total of 12 treatment cycles.
Period Title: Induction Chemoimmunotherapy
Started 34
Completed 19
Not Completed 15
Reason Not Completed
Death             2
Lack of Efficacy             5
Adverse Event             7
Withdrawal by Subject             1
Period Title: Maintenance Lenalidomide
Started 19
Completed 6
Not Completed 13
Reason Not Completed
Lack of Efficacy             5
Adverse Event             8
Arm/Group Title Overall Study Population
Hide Arm/Group Description Patient population with chronic lymphocytic leukemia/small lymphocytic lymphoma with progressive disease in need of therapy after at least 1 prior chemotherapy regimen, but no more than 5 prior unique chemotherapy regimens (retreatment with identical regimen did not count as a unique regimen).
Overall Number of Baseline Participants 34
Hide Baseline Analysis Population Description
Subjects with progressive chronic lymphocytic leukemia/small lymphocytic lymphoma receiving 1-5 prior unique treatment regimens.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 34 participants
67
(48 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Female
10
  29.4%
Male
24
  70.6%
ECOG performance status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
ECOG performance status 0-1 32
ECOG performance status 2 2
[1]
Measure Description: ECOG performance status (PS) evaluated clinically in all patients on a scale from 0-5, with higher ECOG PS indicating worse functional impairment (i.e., ECOG PS of zero = asymptomatic, fully functional patient; ECOG PS of 5 = death).
Disease staging   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Rai stage 1/2 (CLL) 12
Rai stage 3/4 (CLL) 14
Ann Arbor stage 1/2 (SLL) 1
Ann Arbor 3/4 (SLL) 7
[1]
Measure Description:

Rai staging is a clinical evaluation taking into account blood counts and physical exam findings, with staging ranging from 0-4 (more advanced staging corresponding with higher numbers).

Ann Arbor staging is an evaluation of physical exam finding combined with imaging evaluation (usually CT imaging) to determine extent of lymph node enlargement, with staging ranging from 1-4 (more advanced staging corresponding with higher numbers).

Median prior therapies   [1] 
Median (Full Range)
Unit of measure:  Prior therapies
Number Analyzed 34 participants
2
(1 to 4)
[1]
Measure Description: Describes number of unique prior therapies received by subjects, including monoclonal antibody therapy (i.e., single-agent rituximab) or cytotoxic chemotherapy-based therapies. Retreatment with an identical regimen was not counted as a unique therapy. Subjects required at least one cytotoxic chemotherapy-based therapy for eligibility.
Prior therapy with fludarabine  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Prior fludarabine-based therapy 23
No previous fludrarabine exposure 11
Refractory to most recent therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Refractory to most recent therapy 4
Not refractory to most recent therapy 30
Elevated serum lactate dehydrogenase (LDH) level   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Enrollment LDH elevated 20
Enrollment LDH not elevated 14
[1]
Measure Description: Lactate dehydrogenase (LDH) is associated with cell growth and turnover in the body. Higher levels of LDH tend to be associated with more rapid tumor growth and is a marker of higher risk lymphoma/leukemia.
Baseline cytogenetics  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
17p or 11q deletions 11
13q deletion 2
Trisomy 12 8
Normal 3
Unknown 10
Prior therapy with rituximab  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 34 participants
Prior therapy with rituximab 27
No prior therapy with rituximab 7
1.Primary Outcome
Title Progression Free Survival
Hide Description The primary endpoint of this study was progression-free survival (PFS), defined as the number of days from the day of first study drug administration to the day the patient experienced disease progression or death from any cause. Response and progression in cases of small lymphocytic lymphoma(SLL) were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of chronic lymphocytic leukemia (CLL) were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007).
Time Frame 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study was designed to test the null hypothesis that the median PFS with induction BR and maintenance lenalidomide is at most 18 months versus the alternative hypothesis that median PFS is >18 months, at a one-sided significance level of 0.10 with a power of 80%.
Arm/Group Title Induction/Maintenance Chemotherapy
Hide Arm/Group Description:

Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy

Bendamustine: 90 mg/m2/day IV days 1 and 2 every 28 days for 6 cycles

Rituximab: 375 mg/m2 Day 1 every 28 days for 6 cycles

Lenalidomide: 5 mg/day days 1-28 of each 28 day cycle, up to 12 cycles maximum. Dose escalation to 10 mg/day allowed after one cycle as defined in the protocol.

Overall Number of Participants Analyzed 34
Median (95% Confidence Interval)
Unit of Measure: months
18.3
(10.6 to 24.3)
2.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) is defined as the time from the day of first study drug administration until progression of CLL/SLL or death from any cause. PFS is reported as the proportion of participants with PFS up to 42 months.
Time Frame 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Induction/Maintenance Chemotherapy
Hide Arm/Group Description:

Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy

Bendamustine: 90 mg/m2/day IV days 1 and 2 every 28 days for 6 cycles

Rituximab: 375 mg/m2 Day 1 every 28 days for 6 cycles

Lenalidomide: 5 mg/day days 1-28 of each 28 day cycle, up to 12 cycles maximum. Dose escalation to 10 mg/day allowed after one cycle as defined in the protocol.

Overall Number of Participants Analyzed 34
Median (95% Confidence Interval)
Unit of Measure: Proportion of participants
1-year progression-free survival
0.62
(0.47 to 0.80)
2-year progression-free survival
0.35
(0.22 to 0.56)
3-year progression-free survival
0.23
(0.12 to 0.43)
3.Secondary Outcome
Title Objective Response Rate (Complete + Partial Responses)
Hide Description Response and progression in cases of SLL were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of CLL were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). Complete response defined as resolution enlarged lymph nodes, spleen and liver; normalization of blood counts (neutrophils, hemoglobin, platelets); no residual CLL/SLL detectable in the bone marrow. Partial response defined as 50% or more reduction in size of enlarged lymph nodes, liver or spleen; 50% or more improvement of blood counts; 50% or more improvement in the blood lymphocyte count. Progressive disease defined as 50% or more increase in the combined measurements of at least 2 lymph nodes as measured on CT scans or the appearance of new enlarged lymph nodes; 50% of more increase in the size of the spleen or liver; 50% or more increase in blood lymphocyte count.
Time Frame 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Complete Response (CR) Partial Response (PR) Stable Disease Overall Response Rate
Hide Arm/Group Description:
Complete response defined as resolution enlarged lymph nodes, spleen and liver; normalization of blood counts (neutrophils, hemoglobin, platelets); no residual CLL/SLL detectable in the bone marrow.
Partial response defined as 50% or more reduction in size of enlarged lymph nodes, liver or spleen; 50% or more improvement of blood counts; 50% or more improvement in the blood lymphocyte count.
Stable disease includes cases where there has been objective improvement in blood counts and lymph node size, but does not meet criteria for either a complete or partial response.
Includes complete and partial responses.
Overall Number of Participants Analyzed 34 34 34 34
Measure Type: Number
Unit of Measure: participants
7 12 9 19
4.Secondary Outcome
Title Toxicities Observed With Induction Chemotherapy and Maintenance Therapy
Hide Description Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.
Time Frame 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.
Arm/Group Title Induction Chemoimmunotherapy Maintenance
Hide Arm/Group Description:
Bendamustine 90 mg/m2 IV on days 1 & 2 + rituximab 375 mg/m2 IV on day 1 (permitted on day 2 of cycle 1) every 28 days for total of 6 treatment cycles.
Lenalidomide 5-10 mg administered orally daily as continuous therapy for up to 12 treatment cycles (28-day treatment cycles) in patients without disease progression or treatment-related toxicities that would prohibit ongoing treatment.
Overall Number of Participants Analyzed 34 19
Measure Type: Number
Unit of Measure: participants
Grade 3 leukopenia 5 6
Grade 4 leukopenia 5 1
Grade 3 neutropenia 6 7
Grade 4 neutropenia 14 2
Grade 3 anemia 1 0
Grade 3 thrombocytopenia 5 1
Grade 4 thrombocytopenia 2 0
Grade 3 febrile neutropenia 4 1
Grade 3 infection 10 4
Grade 4 infection 1 1
Grade 5 infection 1 0
Grade 3 fatigue 2 0
Grade 4 fatigue 0 1
Grade 3 nausea/emesis 3 0
Grade 3 serum transaminase levels (Gr 3/Gr 4) 4 0
5.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause.
Time Frame 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Overall survival (OS) was measured for all enrolled subjects as the time from the day of first study drug administration until death from any cause.
Arm/Group Title Overall Study Population
Hide Arm/Group Description:
Patient population with chronic lymphocytic leukemia/small lymphocytic lymphoma with progressive disease in need of therapy after at least 1 prior chemotherapy regimen, but no more than 5 prior unique chemotherapy regimens (retreatment with identical regimen did not count as a unique regimen).
Overall Number of Participants Analyzed 34
Median (95% Confidence Interval)
Unit of Measure: months
42.8
(33.7 to 69.5)
Time Frame Adverse event date was captured from the time of study enrollment until at least 30 days following the final dose of study treatment.
Adverse Event Reporting Description Any serious or unexpected adverse event was reported during the entire duration of long-term follow-up.
 
Arm/Group Title Induction Chemoimmunotherapy Maintenance
Hide Arm/Group Description Bendamustine 90 mg/m2 IV on days 1 & 2 + rituximab 375 mg/m2 IV on day 1 (permitted on day 2 of cycle 1) every 28 days for total of 6 treatment cycles. Lenalidomide 5-10 mg administered orally daily as continuous therapy for up to 12 treatment cycles (28-day treatment cycles) in patients without disease progression or treatment-related toxicities that would prohibit ongoing treatment.
All-Cause Mortality
Induction Chemoimmunotherapy Maintenance
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Induction Chemoimmunotherapy Maintenance
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/34 (41.18%)      8/19 (42.11%)    
Blood and lymphatic system disorders     
Grade 4 neutropenia  1 [1]  14/34 (41.18%)  14 2/19 (10.53%)  2
Grade 3 neutropenia  1 [2]  6/34 (17.65%)  6 7/19 (36.84%)  7
Grade 4 thrombocytopenia  1 [3]  2/34 (5.88%)  2 0/19 (0.00%)  0
Grade 3 thrombocytopenia  1 [4]  5/34 (14.71%)  5 1/19 (5.26%)  1
Grade 4 leukopenia  1 [5]  5/34 (14.71%)  5 1/19 (5.26%)  1
Grade 3 leukopenia  1 [6]  5/34 (14.71%)  5 6/19 (31.58%)  6
Grade 3 thrombosis  1  0/34 (0.00%)  0 1/19 (5.26%)  1
Cardiac disorders     
Grade 3 prolonged QTc interval  1  0/34 (0.00%)  0 1/19 (5.26%)  1
Grade 5 heart failure  1  1/34 (2.94%)  1 0/19 (0.00%)  0
Infections and infestations     
Grade 4 febrile neutropenia  1  0/34 (0.00%)  0 0/19 (0.00%)  0
Grade 3 febrile neutropenia  1  4/34 (11.76%)  4 1/19 (5.26%)  1
Grade 5 infections  1  1/34 (2.94%)  1 0/19 (0.00%)  0
Grade 4 infections  1  1/34 (2.94%)  1 1/19 (5.26%)  1
Metabolism and nutrition disorders     
Grade 3 tumor lysis syndrome  1  1/34 (2.94%)  1 0/19 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Second primary malignancy  1 [7]  1/34 (2.94%)  1 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
SAEs included any grade 2-3 unexpected event with at least probable attribution, grade 4-5 toxicity regardless of attribution. Number of events includes worst grade toxicity per patient.
[2]
Includes all events of grade 3 neutropenia, regardless of whether or not resulted in hospitalization of other definition of SAE.
[3]
Includes all events of grade 4 thrombocytopenia, as required by definition of SAE per protocol.
[4]
Includes all events of grade 3 thrombocytopenia, regardless of whether or not resulted in hospitalization of other definition of SAE.
[5]
Includes all events of grade 4 leukopenia, as defined by SAE reporting per protocol.
[6]
Includes all events of grade 3 leukopenia, regardless of whether or not resulted in hospitalization of other definition of SAE.
[7]
Includes events that occurred during treatment and during long-term follow-up phase of treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Induction Chemoimmunotherapy Maintenance
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/34 (100.00%)      19/19 (100.00%)    
Gastrointestinal disorders     
Grade 3 emesis  1 [1]  2/34 (5.88%)  2 0/19 (0.00%)  0
Grade 1-2 nausea  1 [1]  0/34 (0.00%)  0 4/19 (21.05%)  4
Grade 3 diarrhea  1 [1]  3/34 (8.82%)  3 0/19 (0.00%)  0
Grade 1-2 emesis  1 [1]  2/34 (5.88%)  2 1/19 (5.26%)  1
Grade 2 stomatitis  1 [1]  2/34 (5.88%)  2 0/19 (0.00%)  0
General disorders     
Grade 3 fatigue  1 [1]  2/34 (5.88%)  2 0/19 (0.00%)  0
Grade 1-2 fatigue  1 [1]  0/34 (0.00%)  0 6/19 (31.58%)  6
Grade 1-2 night sweats  1 [1]  0/34 (0.00%)  0 3/19 (15.79%)  3
Hepatobiliary disorders     
Grade 3 elevated AST/ALT  1 [1]  4/34 (11.76%)  4 0/19 (0.00%)  0
Grade 1-2 AST/ALT  1 [1]  4/34 (11.76%)  4 0/19 (0.00%)  0
Infections and infestations     
Grade 3 Infections  1 [1]  10/34 (29.41%)  10 4/19 (21.05%)  4
Metabolism and nutrition disorders     
Grade 3 hypophosphatemia  1 [1]  2/34 (5.88%)  2 0/19 (0.00%)  0
Grade 1-2 hyperglycemia  1 [1]  0/34 (0.00%)  0 4/19 (21.05%)  4
Musculoskeletal and connective tissue disorders     
Grade 1-2 musculoskeletal pain  1 [1]  0/34 (0.00%)  0 6/19 (31.58%)  6
Grade 3 pain NOS  1 [1]  0/34 (0.00%)  0 2/19 (10.53%)  2
Nervous system disorders     
Grade 1-2 headache  1  0/34 (0.00%)  0 3/19 (15.79%)  3
Respiratory, thoracic and mediastinal disorders     
Grade 1-2 cough  1 [1]  0/34 (0.00%)  0 4/19 (21.05%)  4
Skin and subcutaneous tissue disorders     
Grade 1-2 rash  1 [1]  5/34 (14.71%)  5 5/19 (26.32%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Worst grade toxicity per patient. Includes toxicities that are expected and not meeting other criteria for serious per protocol.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Julie E. Chang, MD
Organization: University of Wisconsin
Phone: 608-262-3970
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00974233     History of Changes
Other Study ID Numbers: HO08405
RV-CLL/SLL-PI-397
First Submitted: September 9, 2009
First Posted: September 10, 2009
Results First Submitted: May 17, 2016
Results First Posted: July 13, 2017
Last Update Posted: July 13, 2017