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A Randomized, Double-Blind and Placebo-Controlled Study of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela)

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ClinicalTrials.gov Identifier: NCT01569295
Recruitment Status : Active, not recruiting
First Posted : April 3, 2012
Results First Posted : February 27, 2018
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Chronic Lymphocytic Leukemia
Interventions Drug: Idelalisib
Drug: Rituximab
Drug: Bendamustine
Drug: Placebo to match idelalisib
Enrollment 416
Recruitment Details Participants were enrolled at a total of 110 sites in Australia, New Zealand, Europe, Asia and North America. First participant was screened on 15 June 2012 and the last observation for Follow-Up assessment for primary analysis was on 07 October 2015.
Pre-assignment Details A total of 416 participants were analyzed.
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of chronic lymphocytic leukemia (CLL), intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions) Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
Period Title: Overall Study
Started 207 209
Completed 73 [1] 142
Not Completed 134 67
Reason Not Completed
Ongoing in Study             70             23
Adverse Event             27             13
Withdrawal by Subject             20             8
Physician Decision             7             19
Other             4             3
Noncompliance with Study Drug             3             0
Other Anticancer/Experimental Therapy             2             1
Lost to Follow-up             1             0
[1]
Completed = reached primary efficacy endpoint (progressive disease or death)
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab Total
Hide Arm/Group Description Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions) Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions) Total of all reporting groups
Overall Number of Baseline Participants 207 209 416
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) Analysis Set included all participants randomized in the study regardless of whether study drug was administered and with treatment group designated according to initial randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 207 participants 209 participants 416 participants
62  (9.2) 63  (9.8) 62  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 209 participants 416 participants
Female
47
  22.7%
53
  25.4%
100
  24.0%
Male
160
  77.3%
156
  74.6%
316
  76.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 209 participants 416 participants
White
187
  90.3%
190
  90.9%
377
  90.6%
Black or African American
6
   2.9%
4
   1.9%
10
   2.4%
Asian
2
   1.0%
1
   0.5%
3
   0.7%
Other
2
   1.0%
2
   1.0%
4
   1.0%
Not Permitted
10
   4.8%
12
   5.7%
22
   5.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 209 participants 416 participants
Hispanic or Latino
4
   1.9%
5
   2.4%
9
   2.2%
Not Hispanic or Latino
191
  92.3%
188
  90.0%
379
  91.1%
Not Permitted
12
   5.8%
15
   7.2%
27
   6.5%
Missing
0
   0.0%
1
   0.5%
1
   0.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 209 participants 416 participants
Romania
5
   2.4%
6
   2.9%
11
   2.6%
Hungary
24
  11.6%
20
   9.6%
44
  10.6%
United States
37
  17.9%
33
  15.8%
70
  16.8%
Czechia
9
   4.3%
5
   2.4%
14
   3.4%
United Kingdom
27
  13.0%
29
  13.9%
56
  13.5%
Portugal
1
   0.5%
4
   1.9%
5
   1.2%
Russia
22
  10.6%
14
   6.7%
36
   8.7%
Spain
14
   6.8%
18
   8.6%
32
   7.7%
Greece
1
   0.5%
1
   0.5%
2
   0.5%
Canada
0
   0.0%
3
   1.4%
3
   0.7%
Turkey
6
   2.9%
6
   2.9%
12
   2.9%
Belgium
3
   1.4%
7
   3.3%
10
   2.4%
Ireland
1
   0.5%
1
   0.5%
2
   0.5%
Poland
17
   8.2%
22
  10.5%
39
   9.4%
Italy
10
   4.8%
7
   3.3%
17
   4.1%
Australia
8
   3.9%
8
   3.8%
16
   3.8%
France
13
   6.3%
14
   6.7%
27
   6.5%
Croatia
5
   2.4%
9
   4.3%
14
   3.4%
New Zealand
4
   1.9%
2
   1.0%
6
   1.4%
1.Primary Outcome
Title Progression-Free Survival
Hide Description Progression-free survival (PFS) was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. PFS (months) = (minimum (date of disease progression, date of death) - date of randomization + 1)/30.4375
Time Frame Up to 45 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description:
Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions)
Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
Overall Number of Participants Analyzed 207 209
Median (95% Confidence Interval)
Unit of Measure: months
20.8
(16.6 to 26.4)
11.1
(8.9 to 11.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method stratified log-rank test
Comments P-value is adjusted for randomization stratification factors.
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.25 to 0.44
Estimation Comments [Not Specified]
Other Statistical Analysis Hazard Ratio is adjusted for randomization stratification factors.
2.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description

ORR was the percentage of participants who achieved a complete response (CR), CR with incomplete marrow recovery (CRi,) or partial response (PR) and maintained the response for at least 12 weeks. CR was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy.

PR was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors. CRi was defined as all criteria for CR met but with persistent anemia, thrombocytopenia, neutropenia or a hypocellular bone marrow.

Time Frame Up to 45 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description:
Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions)
Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
Overall Number of Participants Analyzed 207 209
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
70.0
(63.3 to 76.2)
45.0
(38.1 to 52.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Odds ratio, 95% Confidence Interval (CI) and p-value were calculated from the CMH Chi-square test stratified by stratification factors in EDC (del17p/TP53, IgHV mutation and disease status).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.09
Confidence Interval (2-Sided) 95%
2.02 to 4.72
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Lymph Node Response Rate
Hide Description Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lesions.
Time Frame Up to 45 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description:
Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions)
Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
Overall Number of Participants Analyzed 207 209
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of particpants
96.9
(93.3 to 98.8)
60.9
(53.7 to 67.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Odds ratio, 95% CI and p-value were calculated from the CMH Chi-square test stratified by stratification factors in EDC (del17p/TP53, IgHV mutation and disease status).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 28.72
Confidence Interval (2-Sided) 95%
10.48 to 78.72
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was defined as the interval from randomization to death from any cause. Overall survival (months) = (date of death - date of randomization + 1)/30.4375.
Time Frame Up to 47 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description:
Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions)
Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
Overall Number of Participants Analyzed 207 209
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
31.6 [1] 
(21.3 to NA)
[1]
Not reached
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0309
Comments [Not Specified]
Method stratified log rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.42 to 0.92
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Complete Response Rate
Hide Description Complete response (CR) rate was defined as the percentage of participants who achieved a CR.
Time Frame Up to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description:
Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions)
Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
Overall Number of Participants Analyzed 207 209
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.4
(0.3 to 4.2)
0
(0 to 1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1223
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame From the date of first dose of study drug until data cut-off 02 May 2016 (approximately 47 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Hide Arm/Group Description Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/mg^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions) Placebo to match idelalisib administered orally twice daily + Rituximab 375 mg/m^2 on Day 1, then 500 mg/ m^2 every 28 days administered intravenously for a total of 6 infusions + Bendamustine 70 mg/m^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions)
All-Cause Mortality
Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   147/207 (71.01%)   94/209 (44.98%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  0/207 (0.00%)  2/209 (0.96%) 
Anaemia  1  6/207 (2.90%)  5/209 (2.39%) 
Autoimmune haemolytic anaemia  1  0/207 (0.00%)  2/209 (0.96%) 
Febrile neutropenia  1  43/207 (20.77%)  10/209 (4.78%) 
Haemolytic anaemia  1  0/207 (0.00%)  1/209 (0.48%) 
Histiocytosis haematophagic  1  0/207 (0.00%)  1/209 (0.48%) 
Immune thrombocytopenic purpura  1  1/207 (0.48%)  1/209 (0.48%) 
Lymphadenopathy  1  0/207 (0.00%)  1/209 (0.48%) 
Neutropenia  1  9/207 (4.35%)  3/209 (1.44%) 
Thrombocytopenia  1  3/207 (1.45%)  0/209 (0.00%) 
Thrombotic thrombocytopenic purpura  1  0/207 (0.00%)  1/209 (0.48%) 
Cardiac disorders     
Acute myocardial infarction  1  0/207 (0.00%)  2/209 (0.96%) 
Atrial fibrillation  1  1/207 (0.48%)  1/209 (0.48%) 
Cardiac arrest  1  0/207 (0.00%)  1/209 (0.48%) 
Cardiac failure  1  0/207 (0.00%)  1/209 (0.48%) 
Cardiac failure congestive  1  1/207 (0.48%)  0/209 (0.00%) 
Left ventricular dysfunction  1  1/207 (0.48%)  0/209 (0.00%) 
Pericardial effusion  1  1/207 (0.48%)  0/209 (0.00%) 
Supraventricular extrasystoles  1  1/207 (0.48%)  0/209 (0.00%) 
Eye disorders     
Retinal detachment  1  1/207 (0.48%)  0/209 (0.00%) 
Vision blurred  1  0/207 (0.00%)  1/209 (0.48%) 
Gastrointestinal disorders     
Abdominal hernia  1  1/207 (0.48%)  0/209 (0.00%) 
Abdominal pain  1  4/207 (1.93%)  2/209 (0.96%) 
Ascites  1  0/207 (0.00%)  2/209 (0.96%) 
Colitis  1  4/207 (1.93%)  1/209 (0.48%) 
Colitis ulcerative  1  1/207 (0.48%)  0/209 (0.00%) 
Constipation  1  1/207 (0.48%)  0/209 (0.00%) 
Diarrhoea  1  12/207 (5.80%)  1/209 (0.48%) 
Diverticular perforation  1  1/207 (0.48%)  0/209 (0.00%) 
Enterovesical fistula  1  1/207 (0.48%)  0/209 (0.00%) 
Gastric haemorrhage  1  1/207 (0.48%)  1/209 (0.48%) 
Gastrointestinal haemorrhage  1  1/207 (0.48%)  0/209 (0.00%) 
Nausea  1  1/207 (0.48%)  2/209 (0.96%) 
Neutropenic colitis  1  0/207 (0.00%)  1/209 (0.48%) 
Pancreatitis  1  2/207 (0.97%)  0/209 (0.00%) 
Pancreatitis acute  1  1/207 (0.48%)  0/209 (0.00%) 
Vomiting  1  0/207 (0.00%)  2/209 (0.96%) 
General disorders     
Asthenia  1  1/207 (0.48%)  2/209 (0.96%) 
Chest pain  1  0/207 (0.00%)  1/209 (0.48%) 
Chills  1  2/207 (0.97%)  0/209 (0.00%) 
Fatigue  1  2/207 (0.97%)  2/209 (0.96%) 
General physical health deterioration  1  1/207 (0.48%)  1/209 (0.48%) 
Malaise  1  1/207 (0.48%)  0/209 (0.00%) 
Multiple organ dysfunction syndrome  1  1/207 (0.48%)  1/209 (0.48%) 
Necrosis  1  1/207 (0.48%)  0/209 (0.00%) 
Pyrexia  1  25/207 (12.08%)  11/209 (5.26%) 
Hepatobiliary disorders     
Bile duct obstruction  1  0/207 (0.00%)  1/209 (0.48%) 
Biliary fistula  1  1/207 (0.48%)  0/209 (0.00%) 
Cholangitis  1  0/207 (0.00%)  1/209 (0.48%) 
Cholecystitis  1  1/207 (0.48%)  0/209 (0.00%) 
Cholelithiasis  1  1/207 (0.48%)  0/209 (0.00%) 
Hepatic failure  1  0/207 (0.00%)  1/209 (0.48%) 
Hepatitis toxic  1  1/207 (0.48%)  0/209 (0.00%) 
Hepatocellular injury  1  2/207 (0.97%)  0/209 (0.00%) 
Hepatotoxicity  1  0/207 (0.00%)  1/209 (0.48%) 
Immune system disorders     
Drug hypersensitivity  1  1/207 (0.48%)  0/209 (0.00%) 
Hypersensitivity  1  2/207 (0.97%)  0/209 (0.00%) 
Infections and infestations     
Aspergillus infection  1  0/207 (0.00%)  1/209 (0.48%) 
Bacteraemia  1  0/207 (0.00%)  1/209 (0.48%) 
Bacterial sepsis  1  1/207 (0.48%)  0/209 (0.00%) 
Brain abscess  1  0/207 (0.00%)  1/209 (0.48%) 
Bronchitis  1  1/207 (0.48%)  5/209 (2.39%) 
Bronchopulmonary aspergillosis  1  1/207 (0.48%)  0/209 (0.00%) 
Campylobacter gastroenteritis  1  1/207 (0.48%)  0/209 (0.00%) 
Cellulitis  1  4/207 (1.93%)  0/209 (0.00%) 
Clostridium difficile infection  1  0/207 (0.00%)  1/209 (0.48%) 
Conjunctivitis bacterial  1  1/207 (0.48%)  0/209 (0.00%) 
Cystitis  1  1/207 (0.48%)  0/209 (0.00%) 
Cytomegalovirus chorioretinitis  1  1/207 (0.48%)  1/209 (0.48%) 
Cytomegalovirus colitis  1  1/207 (0.48%)  0/209 (0.00%) 
Cytomegalovirus enteritis  1  1/207 (0.48%)  0/209 (0.00%) 
Cytomegalovirus infection  1  2/207 (0.97%)  1/209 (0.48%) 
Cytomegalovirus viraemia  1  1/207 (0.48%)  0/209 (0.00%) 
Device related infection  1  2/207 (0.97%)  1/209 (0.48%) 
Ecthyma  1  1/207 (0.48%)  0/209 (0.00%) 
Escherichia sepsis  1  2/207 (0.97%)  0/209 (0.00%) 
Eye infection toxoplasmal  1  1/207 (0.48%)  0/209 (0.00%) 
Fungal infection  1  0/207 (0.00%)  1/209 (0.48%) 
Gastroenteritis  1  2/207 (0.97%)  0/209 (0.00%) 
Gastroenteritis cryptosporidial  1  1/207 (0.48%)  0/209 (0.00%) 
H1N1 influenza  1  1/207 (0.48%)  0/209 (0.00%) 
Haemophilus infection  1  1/207 (0.48%)  0/209 (0.00%) 
Herpes simplex  1  1/207 (0.48%)  0/209 (0.00%) 
Herpes zoster  1  4/207 (1.93%)  1/209 (0.48%) 
Human herpesvirus 6 infection  1  0/207 (0.00%)  1/209 (0.48%) 
Impetigo  1  0/207 (0.00%)  1/209 (0.48%) 
Influenza  1  2/207 (0.97%)  1/209 (0.48%) 
Lower respiratory tract infection  1  6/207 (2.90%)  5/209 (2.39%) 
Lower respiratory tract infection fungal  1  1/207 (0.48%)  0/209 (0.00%) 
Lung infection  1  0/207 (0.00%)  3/209 (1.44%) 
Meningitis bacterial  1  0/207 (0.00%)  1/209 (0.48%) 
Meningitis enteroviral  1  1/207 (0.48%)  0/209 (0.00%) 
Neutropenic infection  1  1/207 (0.48%)  0/209 (0.00%) 
Neutropenic sepsis  1  3/207 (1.45%)  6/209 (2.87%) 
Ophthalmic herpes zoster  1  2/207 (0.97%)  0/209 (0.00%) 
Oral herpes  1  1/207 (0.48%)  0/209 (0.00%) 
Oropharyngitis fungal  1  1/207 (0.48%)  0/209 (0.00%) 
Otitis externa  1  1/207 (0.48%)  0/209 (0.00%) 
Otitis media  1  0/207 (0.00%)  2/209 (0.96%) 
Perineal infection  1  1/207 (0.48%)  0/209 (0.00%) 
Pharyngeal abscess  1  0/207 (0.00%)  1/209 (0.48%) 
Pneumocystis jirovecii infection  1  1/207 (0.48%)  0/209 (0.00%) 
Pneumocystis jirovecii pneumonia  1  3/207 (1.45%)  0/209 (0.00%) 
Pneumonia  1  36/207 (17.39%)  16/209 (7.66%) 
Pneumonia bacterial  1  0/207 (0.00%)  1/209 (0.48%) 
Pneumonia cytomegaloviral  1  1/207 (0.48%)  1/209 (0.48%) 
Pneumonia pseudomonal  1  2/207 (0.97%)  0/209 (0.00%) 
Pneumonia viral  1  0/207 (0.00%)  1/209 (0.48%) 
Pulmonary mycosis  1  0/207 (0.00%)  1/209 (0.48%) 
Pulmonary sepsis  1  1/207 (0.48%)  0/209 (0.00%) 
Reiter's syndrome  1  1/207 (0.48%)  0/209 (0.00%) 
Respiratory syncytial virus infection  1  1/207 (0.48%)  0/209 (0.00%) 
Respiratory tract infection  1  3/207 (1.45%)  5/209 (2.39%) 
Rhinovirus infection  1  1/207 (0.48%)  0/209 (0.00%) 
Sepsis  1  10/207 (4.83%)  4/209 (1.91%) 
Septic shock  1  5/207 (2.42%)  1/209 (0.48%) 
Sinusitis  1  2/207 (0.97%)  0/209 (0.00%) 
Soft tissue infection  1  1/207 (0.48%)  0/209 (0.00%) 
Tonsillitis  1  1/207 (0.48%)  0/209 (0.00%) 
Tuberculosis  1  1/207 (0.48%)  0/209 (0.00%) 
Upper respiratory tract infection  1  0/207 (0.00%)  4/209 (1.91%) 
Upper respiratory tract infection bacterial  1  1/207 (0.48%)  0/209 (0.00%) 
Urinary tract infection  1  5/207 (2.42%)  3/209 (1.44%) 
Urinary tract infection bacterial  1  0/207 (0.00%)  1/209 (0.48%) 
Urosepsis  1  2/207 (0.97%)  1/209 (0.48%) 
Viral infection  1  0/207 (0.00%)  1/209 (0.48%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/207 (0.48%)  0/209 (0.00%) 
Cervical vertebral fracture  1  1/207 (0.48%)  0/209 (0.00%) 
Eye injury  1  0/207 (0.00%)  1/209 (0.48%) 
Femur fracture  1  1/207 (0.48%)  1/209 (0.48%) 
Infusion related reaction  1  2/207 (0.97%)  3/209 (1.44%) 
Periprosthetic fracture  1  1/207 (0.48%)  0/209 (0.00%) 
Wrist fracture  1  1/207 (0.48%)  0/209 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  1/207 (0.48%)  0/209 (0.00%) 
Aspartate aminotransferase increased  1  1/207 (0.48%)  0/209 (0.00%) 
Blood creatinine increased  1  1/207 (0.48%)  0/209 (0.00%) 
Blood lactate dehydrogenase increased  1  0/207 (0.00%)  1/209 (0.48%) 
International normalised ratio increased  1  1/207 (0.48%)  0/209 (0.00%) 
Neutrophil count decreased  1  1/207 (0.48%)  0/209 (0.00%) 
Polyomavirus test positive  1  1/207 (0.48%)  0/209 (0.00%) 
Transaminases increased  1  1/207 (0.48%)  0/209 (0.00%) 
Metabolism and nutrition disorders     
Cachexia  1  1/207 (0.48%)  0/209 (0.00%) 
Decreased appetite  1  1/207 (0.48%)  0/209 (0.00%) 
Dehydration  1  1/207 (0.48%)  1/209 (0.48%) 
Diabetes mellitus inadequate control  1  1/207 (0.48%)  0/209 (0.00%) 
Hypercalcaemia  1  0/207 (0.00%)  1/209 (0.48%) 
Hyperglycaemia  1  1/207 (0.48%)  0/209 (0.00%) 
Hypoalbuminaemia  1  1/207 (0.48%)  0/209 (0.00%) 
Hypokalaemia  1  1/207 (0.48%)  1/209 (0.48%) 
Hyponatraemia  1  2/207 (0.97%)  0/209 (0.00%) 
Malnutrition  1  1/207 (0.48%)  0/209 (0.00%) 
Tumour lysis syndrome  1  3/207 (1.45%)  2/209 (0.96%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/207 (0.48%)  0/209 (0.00%) 
Chondritis  1  1/207 (0.48%)  0/209 (0.00%) 
Chondrocalcinosis  1  1/207 (0.48%)  0/209 (0.00%) 
Myalgia  1  1/207 (0.48%)  0/209 (0.00%) 
Polyarthritis  1  1/207 (0.48%)  0/209 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  0/207 (0.00%)  2/209 (0.96%) 
Basal cell carcinoma  1  3/207 (1.45%)  0/209 (0.00%) 
Bladder cancer  1  1/207 (0.48%)  0/209 (0.00%) 
Bowen's disease  1  1/207 (0.48%)  0/209 (0.00%) 
Chronic lymphocytic leukaemia  1  1/207 (0.48%)  0/209 (0.00%) 
Gastric cancer  1  0/207 (0.00%)  1/209 (0.48%) 
Leiomyosarcoma  1  1/207 (0.48%)  0/209 (0.00%) 
Lip squamous cell carcinoma  1  1/207 (0.48%)  0/209 (0.00%) 
Lung adenocarcinoma  1  1/207 (0.48%)  1/209 (0.48%) 
Lung neoplasm malignant  1  1/207 (0.48%)  0/209 (0.00%) 
Malignant melanoma  1  2/207 (0.97%)  0/209 (0.00%) 
Meningioma  1  1/207 (0.48%)  0/209 (0.00%) 
Myelodysplastic syndrome  1  2/207 (0.97%)  0/209 (0.00%) 
Nasopharyngeal cancer  1  0/207 (0.00%)  1/209 (0.48%) 
Oesophageal carcinoma  1  1/207 (0.48%)  0/209 (0.00%) 
Prostate cancer  1  2/207 (0.97%)  0/209 (0.00%) 
Rectal adenocarcinoma  1  1/207 (0.48%)  0/209 (0.00%) 
Squamous cell carcinoma  1  1/207 (0.48%)  5/209 (2.39%) 
Squamous cell carcinoma of lung  1  1/207 (0.48%)  0/209 (0.00%) 
Squamous cell carcinoma of skin  1  3/207 (1.45%)  2/209 (0.96%) 
T-cell lymphoma  1  0/207 (0.00%)  1/209 (0.48%) 
Transitional cell carcinoma  1  1/207 (0.48%)  0/209 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage  1  1/207 (0.48%)  0/209 (0.00%) 
Dizziness  1  1/207 (0.48%)  0/209 (0.00%) 
Headache  1  0/207 (0.00%)  1/209 (0.48%) 
Ischaemic stroke  1  1/207 (0.48%)  0/209 (0.00%) 
Post herpetic neuralgia  1  0/207 (0.00%)  1/209 (0.48%) 
Seizure  1  1/207 (0.48%)  0/209 (0.00%) 
Syncope  1  1/207 (0.48%)  0/209 (0.00%) 
Psychiatric disorders     
Anxiety  1  0/207 (0.00%)  1/209 (0.48%) 
Confusional state  1  1/207 (0.48%)  0/209 (0.00%) 
Delusion  1  1/207 (0.48%)  0/209 (0.00%) 
Mental status changes  1  0/207 (0.00%)  1/209 (0.48%) 
Mood swings  1  1/207 (0.48%)  0/209 (0.00%) 
Panic attack  1  1/207 (0.48%)  0/209 (0.00%) 
Personality change  1  1/207 (0.48%)  0/209 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/207 (0.48%)  1/209 (0.48%) 
Calculus urinary  1  0/207 (0.00%)  1/209 (0.48%) 
Haematuria  1  1/207 (0.48%)  0/209 (0.00%) 
Renal colic  1  2/207 (0.97%)  0/209 (0.00%) 
Renal failure  1  0/207 (0.00%)  1/209 (0.48%) 
Urinary incontinence  1  1/207 (0.48%)  0/209 (0.00%) 
Reproductive system and breast disorders     
Cervical polyp  1  1/207 (0.48%)  0/209 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/207 (0.00%)  1/209 (0.48%) 
Bronchial hyperreactivity  1  1/207 (0.48%)  0/209 (0.00%) 
Chronic obstructive pulmonary disease  1  0/207 (0.00%)  1/209 (0.48%) 
Cough  1  4/207 (1.93%)  2/209 (0.96%) 
Dyspnoea  1  3/207 (1.45%)  3/209 (1.44%) 
Epistaxis  1  0/207 (0.00%)  1/209 (0.48%) 
Hypoxia  1  2/207 (0.97%)  0/209 (0.00%) 
Lung disorder  1  0/207 (0.00%)  1/209 (0.48%) 
Pleural effusion  1  2/207 (0.97%)  0/209 (0.00%) 
Pneumonia aspiration  1  1/207 (0.48%)  0/209 (0.00%) 
Pneumonitis  1  4/207 (1.93%)  0/209 (0.00%) 
Pneumothorax  1  0/207 (0.00%)  1/209 (0.48%) 
Pulmonary embolism  1  2/207 (0.97%)  5/209 (2.39%) 
Pulmonary pain  1  0/207 (0.00%)  1/209 (0.48%) 
Respiratory distress  1  1/207 (0.48%)  0/209 (0.00%) 
Respiratory failure  1  2/207 (0.97%)  0/209 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis atopic  1  1/207 (0.48%)  0/209 (0.00%) 
Dermatitis exfoliative  1  2/207 (0.97%)  0/209 (0.00%) 
Drug reaction with eosinophilia and systemic symptoms  1  1/207 (0.48%)  0/209 (0.00%) 
Rash macular  1  1/207 (0.48%)  0/209 (0.00%) 
Rash maculo-papular  1  1/207 (0.48%)  0/209 (0.00%) 
Stevens-Johnson syndrome  1  2/207 (0.97%)  0/209 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/207 (0.48%)  0/209 (0.00%) 
Hypotension  1  2/207 (0.97%)  2/209 (0.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Idelalisib + Bendamustine + Rituximab Placebo + Bendamustine + Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   198/207 (95.65%)   196/209 (93.78%) 
Blood and lymphatic system disorders     
Anaemia  1  53/207 (25.60%)  47/209 (22.49%) 
Leukopenia  1  17/207 (8.21%)  10/209 (4.78%) 
Neutropenia  1  129/207 (62.32%)  113/209 (54.07%) 
Thrombocytopenia  1  41/207 (19.81%)  46/209 (22.01%) 
Gastrointestinal disorders     
Abdominal pain  1  18/207 (8.70%)  12/209 (5.74%) 
Constipation  1  32/207 (15.46%)  35/209 (16.75%) 
Diarrhoea  1  81/207 (39.13%)  47/209 (22.49%) 
Dyspepsia  1  13/207 (6.28%)  8/209 (3.83%) 
Nausea  1  56/207 (27.05%)  72/209 (34.45%) 
Vomiting  1  34/207 (16.43%)  31/209 (14.83%) 
General disorders     
Asthenia  1  22/207 (10.63%)  20/209 (9.57%) 
Chills  1  21/207 (10.14%)  13/209 (6.22%) 
Fatigue  1  42/207 (20.29%)  52/209 (24.88%) 
Oedema peripheral  1  16/207 (7.73%)  18/209 (8.61%) 
Pyrexia  1  78/207 (37.68%)  55/209 (26.32%) 
Immune system disorders     
Hypogammaglobulinaemia  1  12/207 (5.80%)  10/209 (4.78%) 
Infections and infestations     
Bronchitis  1  15/207 (7.25%)  8/209 (3.83%) 
Lower respiratory tract infection  1  12/207 (5.80%)  10/209 (4.78%) 
Nasopharyngitis  1  15/207 (7.25%)  11/209 (5.26%) 
Pneumonia  1  25/207 (12.08%)  12/209 (5.74%) 
Respiratory tract infection  1  6/207 (2.90%)  11/209 (5.26%) 
Sinusitis  1  16/207 (7.73%)  13/209 (6.22%) 
Upper respiratory tract infection  1  36/207 (17.39%)  21/209 (10.05%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  29/207 (14.01%)  46/209 (22.01%) 
Investigations     
Alanine aminotransferase increased  1  32/207 (15.46%)  3/209 (1.44%) 
Aspartate aminotransferase increased  1  19/207 (9.18%)  2/209 (0.96%) 
Weight decreased  1  21/207 (10.14%)  12/209 (5.74%) 
Metabolism and nutrition disorders     
Decreased appetite  1  22/207 (10.63%)  15/209 (7.18%) 
Hypokalaemia  1  19/207 (9.18%)  16/209 (7.66%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  25/207 (12.08%)  16/209 (7.66%) 
Back pain  1  15/207 (7.25%)  15/209 (7.18%) 
Nervous system disorders     
Headache  1  20/207 (9.66%)  21/209 (10.05%) 
Psychiatric disorders     
Anxiety  1  6/207 (2.90%)  12/209 (5.74%) 
Insomnia  1  19/207 (9.18%)  13/209 (6.22%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  47/207 (22.71%)  47/209 (22.49%) 
Dyspnoea  1  20/207 (9.66%)  26/209 (12.44%) 
Oropharyngeal pain  1  10/207 (4.83%)  14/209 (6.70%) 
Productive cough  1  17/207 (8.21%)  12/209 (5.74%) 
Skin and subcutaneous tissue disorders     
Night sweats  1  17/207 (8.21%)  8/209 (3.83%) 
Pruritus  1  16/207 (7.73%)  12/209 (5.74%) 
Rash  1  35/207 (16.91%)  28/209 (13.40%) 
Vascular disorders     
Hypertension  1  11/207 (5.31%)  5/209 (2.39%) 
Hypotension  1  14/207 (6.76%)  12/209 (5.74%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
Publications:
Zelenetz AD, Robak T, et al. Idelalisib Plus Bendamustine and Rituximab (BR) Is Superior to BR Alone in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of a Phase 3 Randomized Double-Blind Placebo-Controlled Study. American Society ofHematology (ASH) 57th Annual Meeting & Exposition; 5-8 December 2015; Orlando, FL.
Barrientos JC, Brown JR, et al. Results of a Randomized Double-Blind Placebo-Controlled Phase 3 study Evaluating Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL and Adverse Prognostic Features. American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; 3-7 June 2016; Chicago, IL.
Hillmen, P, Ferra C, et al. Idelalisib in Combination with Bendamustine and Rituximab Improves Overall Survival in Patients with Relapsed/Refractory CLL: Interim Results of a Phase 3 Randomized Double-Blind Placebo-Controlled Study. European Hematology Association (EHA) 21st Annual Meeting; 9-12 June 2016; Copenhagen, Denmark.
Zelenetz AD, Brown JR et al. Updated Analysis of Overall Survival in Randomized Phase III Study of Idelalisib in Combination with Bendamustine and Rituximab in Patients with Relapsed/Refractory CLL. American Society of Hematology (ASH) 58th Annual Meeting & Exposition; 3-6 December 2016; San Diego, CA
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01569295     History of Changes
Other Study ID Numbers: GS-US-312-0115
2011-006292-20 ( EudraCT Number )
First Submitted: March 27, 2012
First Posted: April 3, 2012
Results First Submitted: December 18, 2017
Results First Posted: February 27, 2018
Last Update Posted: January 16, 2019