A Randomized, Double-Blind, Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL)
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01539512
Collaborator
(none)
220
72
2
24
3.1
0.1
Study Details
Study Description
Brief Summary
This Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect of idelalisib in combination with rituximab on the onset, magnitude, and duration of tumor control in participants previously treated for chronic lymphocytic leukemia (CLL). Eligible patients will be randomized with a 1:1 ratio into 1 of the 2 treatment arms to receive either idelalisib plus rituximab or placebo plus rituximab. Participants who are tolerating primary study therapy but experience definitive CLL progression are eligible to receive active idelalisib therapy in the extension study, GS-US-312-0117.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
220 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia
Study Start Date
:
Apr 1, 2012
Actual Primary Completion Date
:
Oct 1, 2013
Actual Study Completion Date
:
Apr 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Idelalisib + rituximab Participants will receive idelalisib plus rituximab |
Drug: Idelalisib
Idelalisib 150 mg tablet administered orally twice daily
Other Names:
Drug: Rituximab
Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter
Other Names:
|
| Placebo Comparator: Placebo + rituximab Participants will receive placebo to match idelalisib plus rituximab |
Drug: Rituximab
Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter
Other Names:
Drug: Placebo to match idelalisib
Placebo to match idelalisib administered orally twice daily
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival [Up to 17 months]
Progression-free survival was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL.
Secondary Outcome Measures
- Overall Response Rate [Up to 17 months]
Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response. Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. Partial response 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.
- Lymph Node Response Rate [Up to 17 months]
Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the SPD of index lymph nodes.
- Overall Survival [Up to 17 months]
Overall survival was defined as the interval from randomization to death from any cause.
- Complete Response Rate [Up to 17 months]
Complete response rate was defined as the percentage of participants who achieved a complete response.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion:
-
Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy
-
Require therapy for CLL
-
Have experienced CLL progression < 24 months since the completion of the last prior therapy
-
Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clearview Cancer Institute | Huntsville | Alabama | United States | 35805 |
| 2 | Arizona Oncology Associates | Tucson | Arizona | United States | 85704 |
| 3 | University of California, San Diego- Moores Cancer Center | La Jolla | California | United States | 92093 |
| 4 | Ventura County Hematology Oncology Specialists | Oxnard | California | United States | 93030 |
| 5 | UCLA | Santa Monica | California | United States | 90404 |
| 6 | Stanford Cancer Center | Stanford | California | United States | 94305 |
| 7 | Rocky Mountain Blood and Marrow Transplant Program | Denver | Colorado | United States | 80218 |
| 8 | Rocky Mountain Cancer Center | Denver | Colorado | United States | 80218 |
| 9 | Georgetown University Medical Center Lombardi Cancer Center | Washington | District of Columbia | United States | 20057 |
| 10 | Collaborative Medical Research Corporation | Boynton Beach | Florida | United States | 33435 |
| 11 | Collaborative Research Group LLC | Boynton Beach | Florida | United States | 33435 |
| 12 | Florida Cancer Specialists | Fort Myers | Florida | United States | 33916 |
| 13 | University of Florida | Gainesville | Florida | United States | 32610 |
| 14 | Florida Cancer Specialists | Saint Petersburg | Florida | United States | 33705 |
| 15 | Winship Cancer Institute at Emory University | Atlanta | Georgia | United States | 30322 |
| 16 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 17 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 18 | Hematology Oncology Associates of Northern New Jersey | Morristown | New Jersey | United States | 07962 |
| 19 | Long Island Jewish Medical Center | New Hyde Park | New York | United States | 11042 |
| 20 | Weill Cornell Medical College | New York | New York | United States | 10021 |
| 21 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 22 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 23 | Willamette Valley Cancer Center | Springfield | Oregon | United States | 97477 |
| 24 | Northwest Cancer Specialists, PC | Tualatin | Oregon | United States | 97062 |
| 25 | Cancer Centers of the Carolinas | Greenville | South Carolina | United States | 29605 |
| 26 | Sarah Cannon Cancer Center | Nashville | Tennessee | United States | 37203 |
| 27 | Texas Oncology, P.A. | Fort Worth | Texas | United States | 76104 |
| 28 | M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 29 | Cancer Care Network of South Texas | San Antonio | Texas | United States | 78217 |
| 30 | Virginia Cancer Specialists, PC | Fairfax | Virginia | United States | 22031 |
| 31 | Oncology and Hematology Associates of Southwest Virginia, Inc | Roanoke | Virginia | United States | 24014 |
| 32 | Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109-1024 |
| 33 | Yakima Valley Memorial Hospital / North Star Lodge | Yakima | Washington | United States | 98902 |
| 34 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 35 | Hôpital Henri Mondor | Creteil | France | 94010 | |
| 36 | Centre Hospitalier Régional Universitaire de Lille (CHRU) | Lille | France | 59045 | |
| 37 | Hôpital Emile Muller | Mulhouse | France | 68100 | |
| 38 | Centre Hospitalier Lyon Sud | Pierre Benite | France | 69495 | |
| 39 | Hôpital Pontchaillou | Rennes | France | 35019 | |
| 40 | Centre Henri Becquerel | Rouen | France | 76038 | |
| 41 | Hopital Purpan | Toulouse | France | 31059 | |
| 42 | Gemeinschaftspraxis Hämatologie-Onkologie | Dresden | Germany | 1307 | |
| 43 | Internistische Gemeinschaftspraxis | Erlangen | Germany | 91052 | |
| 44 | Universitätsklinikum Köln | Köln | Germany | 50937 | |
| 45 | Stauferklinikum Schwäb. Gmünd | Mutlangen | Germany | 73557 | |
| 46 | Hämatologische/Onkologische Gemeinschaftspraxis Dr. Peter Schmidt / Dr. Holger Klaproth | Neunkirchen | Germany | 66538 | |
| 47 | Universitätsklinikum Ulm | Ulm | Germany | 89081 | |
| 48 | Ospedale Oncologico Regionale A. Businco | Cagliari | Italy | 9121 | |
| 49 | Ospedale San Raffaele S.r.l. | Milano | Italy | 20132 | |
| 50 | Azienda Ospedaliera Città della Salute e della Scienza di Torino | Torino | Italy | 10126 | |
| 51 | Royal Bournemouth Hospital | Bournemouth | United Kingdom | BH7 7DW | |
| 52 | Addenbrooke's Hospital | Cambridge | United Kingdom | CB2 0QQ | |
| 53 | University Hospital of Wales | Cardiff | United Kingdom | CF14 4XW | |
| 54 | Castle Hill Hospital | Cottingham | United Kingdom | HU10 6ED | |
| 55 | Dorset County Hospital | Dorchester | United Kingdom | DT1 2JY | |
| 56 | Western General Hospital | Edinburgh | United Kingdom | EH4 2XU | |
| 57 | Northwick Park Hospital | Harrow | United Kingdom | HA1 3UJ | |
| 58 | St James's University Hospital | Leeds | United Kingdom | LS9 7TF | |
| 59 | Royal Liverpool University Hospital | Liverpool | United Kingdom | L7 8XP | |
| 60 | King's College Hospital | London | United Kingdom | SE5 9RS | |
| 61 | Hammersmith Hospital | London | United Kingdom | W12 0NN | |
| 62 | Sarah Cannon Research Institute UK | London | United Kingdom | W1G 6AD | |
| 63 | Freeman Hospital | Newcastle upon Tyne | United Kingdom | NE7 7DN | |
| 64 | Princess Royal University Hospital | Orpington | United Kingdom | BR6 8ND | |
| 65 | Salisbury District Hospital | Salisbury | United Kingdom | SP2 8BJ | |
| 66 | Southampton General Hospital | Southampton | United Kingdom | SO16 6YD | |
| 67 | Royal Marsden Hospital | Sutton | United Kingdom | SM2 5PT | |
| 68 | Great Western Hospital | Swindon | United Kingdom | SN3 6BB | |
| 69 | Torbay District General Hospital | Torquay | United Kingdom | TQ2 7AA | |
| 70 | Royal Cornwall Hospital | Truro | United Kingdom | TR1 3LJ | |
| 71 | New Cross Hospital | Wolverhampton | United Kingdom | WV10 0QP | |
| 72 | Yeovil District Hospital | Yeovil | United Kingdom | BA21 4AT |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Thomas Jahn, MD, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01539512
Other Study ID Numbers:
- GS-US-312-0116
- 2011-005180-24
First Posted:
Feb 27, 2012
Last Update Posted:
May 14, 2019
Last Verified:
Apr 1, 2015
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Gilead Sciences
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at a total of 53 study sites in the United States and Europe. The first participant was screened on 03 April 2012. The last study visit occurred on 20 April 2014. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab |
|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) |
| Period Title: Overall Study | ||
| STARTED | 110 | 110 |
| COMPLETED | 87 | 97 |
| NOT COMPLETED | 23 | 13 |
Baseline Characteristics
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab | Total |
|---|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Total of all reporting groups |
| Overall Participants | 110 | 110 | 220 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
71
(7.7)
|
70
(8.1)
|
71
(7.9)
|
| Age, Customized (participants) [Number] | |||
| < 65 years |
21
19.1%
|
27
24.5%
|
48
21.8%
|
| ≥ 65 years |
89
80.9%
|
83
75.5%
|
172
78.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
34
30.9%
|
42
38.2%
|
76
34.5%
|
| Male |
76
69.1%
|
68
61.8%
|
144
65.5%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Hispanic or Latino |
3
2.7%
|
2
1.8%
|
5
2.3%
|
| Not Hispanic or Latino |
101
91.8%
|
102
92.7%
|
203
92.3%
|
| Not Permitted |
6
5.5%
|
6
5.5%
|
12
5.5%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
100
90.9%
|
98
89.1%
|
198
90%
|
| Black or African American |
3
2.7%
|
3
2.7%
|
6
2.7%
|
| Other |
2
1.8%
|
2
1.8%
|
4
1.8%
|
| Not Permitted |
5
4.5%
|
7
6.4%
|
12
5.5%
|
| Region of Enrollment (participants) [Number] | |||
| France |
3
2.7%
|
3
2.7%
|
6
2.7%
|
| Germany |
7
6.4%
|
5
4.5%
|
12
5.5%
|
| Italy |
2
1.8%
|
5
4.5%
|
7
3.2%
|
| United Kingdom |
18
16.4%
|
14
12.7%
|
32
14.5%
|
| United States |
80
72.7%
|
83
75.5%
|
163
74.1%
|
| Karnofsky Performance Status (participants) [Number] | |||
| 40 |
1
0.9%
|
1
0.9%
|
2
0.9%
|
| 50 |
3
2.7%
|
4
3.6%
|
7
3.2%
|
| 60 |
6
5.5%
|
5
4.5%
|
11
5%
|
| 70 |
20
18.2%
|
13
11.8%
|
33
15%
|
| 80 |
42
38.2%
|
46
41.8%
|
88
40%
|
| 90 |
23
20.9%
|
28
25.5%
|
51
23.2%
|
| 100 |
15
13.6%
|
13
11.8%
|
28
12.7%
|
| Time Since Diagnosis (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
108.3
(62.28)
|
106.4
(52.73)
|
107.4
(57.58)
|
| Rai Stage at Screening (participants) [Number] | |||
| Rai Stage 0 |
0
0%
|
1
0.9%
|
1
0.5%
|
| Rai Stage 1 |
18
16.4%
|
19
17.3%
|
37
16.8%
|
| Rai Stage 2 |
16
14.5%
|
10
9.1%
|
26
11.8%
|
| Rai Stage 3 |
22
20%
|
18
16.4%
|
40
18.2%
|
| Rai Stage 4 |
48
43.6%
|
54
49.1%
|
102
46.4%
|
| Missing |
6
5.5%
|
8
7.3%
|
14
6.4%
|
| Binet Stage at Screening (participants) [Number] | |||
| Binet Stage A |
7
6.4%
|
4
3.6%
|
11
5%
|
| Binet Stage B |
29
26.4%
|
32
29.1%
|
61
27.7%
|
| Binet Stage C |
63
57.3%
|
60
54.5%
|
123
55.9%
|
| Missing |
11
10%
|
14
12.7%
|
25
11.4%
|
Outcome Measures
| Title | Progression-Free Survival |
|---|---|
| Description | Progression-free survival was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL. |
| Time Frame | Up to 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Analysis Set: randomized participants with treatment group designated according to initial randomization. |
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab |
|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) |
| Measure Participants | 110 | 110 |
| Median (95% Confidence Interval) [months] |
NA
|
5.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Idelalisib + Rituximab, Placebo + Rituximab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | Log Rank | |
| Comments | P-value is from stratified log-rank test, adjusted for randomization stratification factors. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.18 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 0.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Response Rate |
|---|---|
| Description | Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response. Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. Partial response 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. |
| Time Frame | Up to 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set: randomized participants with treatment group designated according to initial randomization. |
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab |
|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) |
| Measure Participants | 110 | 110 |
| Number (95% Confidence Interval) [percentage of participants] |
74.5
67.7%
|
14.5
13.2%
|
| Title | Lymph Node Response Rate |
|---|---|
| Description | Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the SPD of index lymph nodes. |
| Time Frame | Up to 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set: randomized participants with treatment group designated according to initial randomization |
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab |
|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) |
| Measure Participants | 110 | 110 |
| Number (95% Confidence Interval) [percentage of participants] |
92.2
83.8%
|
5.9
5.4%
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival was defined as the interval from randomization to death from any cause. |
| Time Frame | Up to 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set: randomized participants with treatment group designated according to initial randomization. |
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab |
|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) |
| Measure Participants | 110 | 110 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Idelalisib + Rituximab, Placebo + Rituximab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) 95% 0.11 to 0.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Complete Response Rate |
|---|---|
| Description | Complete response rate was defined as the percentage of participants who achieved a complete response. |
| Time Frame | Up to 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set: randomized participants with treatment group designated according to initial randomization. |
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab |
|---|---|---|
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) |
| Measure Participants | 110 | 110 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | During study treatment plus 30 days (up to 2 years) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set: randomized participants who received at least 1 dose of study drug, with treatment assignments designated according to the actual treatment received. | |||
| Arm/Group Title | Idelalisib + Rituximab | Placebo + Rituximab | ||
| Arm/Group Description | Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter) | ||
All Cause Mortality |
||||
| Idelalisib + Rituximab | Placebo + Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Idelalisib + Rituximab | Placebo + Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 65/110 (59.1%) | 43/108 (39.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Febrile neutropenia | 5/110 (4.5%) | 6/108 (5.6%) | ||
| Haemolytic anaemia | 1/110 (0.9%) | 0/108 (0%) | ||
| Neutropenia | 3/110 (2.7%) | 0/108 (0%) | ||
| Pancytopenia | 0/110 (0%) | 1/108 (0.9%) | ||
| Splenic infarction | 0/110 (0%) | 1/108 (0.9%) | ||
| Thrombocytopenia | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/110 (0.9%) | 0/108 (0%) | ||
| Cardiac failure | 0/110 (0%) | 1/108 (0.9%) | ||
| Cardiac failure congestive | 1/110 (0.9%) | 0/108 (0%) | ||
| Left ventricular failure | 0/110 (0%) | 1/108 (0.9%) | ||
| Myocardial infarction | 0/110 (0%) | 1/108 (0.9%) | ||
| Right ventricular failure | 1/110 (0.9%) | 0/108 (0%) | ||
| Endocrine disorders | ||||
| Inappropriate antidiuretic hormone secretion | 1/110 (0.9%) | 0/108 (0%) | ||
| Eye disorders | ||||
| Eye pain | 1/110 (0.9%) | 0/108 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Colitis | 4/110 (3.6%) | 0/108 (0%) | ||
| Constipation | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Diarrhoea | 8/110 (7.3%) | 0/108 (0%) | ||
| Gastric mucosa erythema | 1/110 (0.9%) | 0/108 (0%) | ||
| Nausea | 1/110 (0.9%) | 0/108 (0%) | ||
| Oral pain | 1/110 (0.9%) | 0/108 (0%) | ||
| Vomiting | 1/110 (0.9%) | 0/108 (0%) | ||
| General disorders | ||||
| Asthenia | 2/110 (1.8%) | 3/108 (2.8%) | ||
| Chest pain | 1/110 (0.9%) | 0/108 (0%) | ||
| Chills | 0/110 (0%) | 1/108 (0.9%) | ||
| Device dislocation | 1/110 (0.9%) | 0/108 (0%) | ||
| Fatigue | 0/110 (0%) | 1/108 (0.9%) | ||
| General physical health deterioration | 0/110 (0%) | 1/108 (0.9%) | ||
| Multi-organ failure | 0/110 (0%) | 1/108 (0.9%) | ||
| Non-cardiac chest pain | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Oedema peripheral | 0/110 (0%) | 2/108 (1.9%) | ||
| Pyrexia | 10/110 (9.1%) | 3/108 (2.8%) | ||
| Infections and infestations | ||||
| Abscess limb | 0/110 (0%) | 1/108 (0.9%) | ||
| Alpha haemolytic streptococcal infection | 1/110 (0.9%) | 0/108 (0%) | ||
| Bacteraemia | 0/110 (0%) | 1/108 (0.9%) | ||
| Bronchitis | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Bronchopulmonary aspergillosis | 1/110 (0.9%) | 0/108 (0%) | ||
| Cellulitis | 1/110 (0.9%) | 4/108 (3.7%) | ||
| Diverticulitis | 1/110 (0.9%) | 0/108 (0%) | ||
| Epididymitis | 1/110 (0.9%) | 0/108 (0%) | ||
| Fungal oesophagitis | 0/110 (0%) | 1/108 (0.9%) | ||
| Gastroenteritis | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Herpes simplex | 0/110 (0%) | 1/108 (0.9%) | ||
| Herpes zoster disseminated | 1/110 (0.9%) | 0/108 (0%) | ||
| Infection | 1/110 (0.9%) | 0/108 (0%) | ||
| Listeriosis | 0/110 (0%) | 1/108 (0.9%) | ||
| Lower respiratory tract infection | 3/110 (2.7%) | 1/108 (0.9%) | ||
| Lung infection | 3/110 (2.7%) | 1/108 (0.9%) | ||
| Mucosal infection | 0/110 (0%) | 1/108 (0.9%) | ||
| Neutropenic sepsis | 2/110 (1.8%) | 0/108 (0%) | ||
| Oral herpes | 1/110 (0.9%) | 0/108 (0%) | ||
| Pneumocystis jirovecii pneumonia | 4/110 (3.6%) | 1/108 (0.9%) | ||
| Pneumonia | 13/110 (11.8%) | 10/108 (9.3%) | ||
| Pneumonia fungal | 2/110 (1.8%) | 0/108 (0%) | ||
| Pneumonia legionella | 0/110 (0%) | 1/108 (0.9%) | ||
| Pneumonia pseudomonal | 1/110 (0.9%) | 0/108 (0%) | ||
| Respiratory tract infection | 0/110 (0%) | 1/108 (0.9%) | ||
| Sepsis | 7/110 (6.4%) | 3/108 (2.8%) | ||
| Sepsis syndrome | 2/110 (1.8%) | 0/108 (0%) | ||
| Septic shock | 0/110 (0%) | 2/108 (1.9%) | ||
| Soft tissue infection | 0/110 (0%) | 1/108 (0.9%) | ||
| Stenotrophomonas infection | 1/110 (0.9%) | 0/108 (0%) | ||
| Upper respiratory tract infection | 1/110 (0.9%) | 2/108 (1.9%) | ||
| Urinary tract infection | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Urosepsis | 1/110 (0.9%) | 0/108 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Femur fracture | 0/110 (0%) | 1/108 (0.9%) | ||
| Hip fracture | 0/110 (0%) | 1/108 (0.9%) | ||
| Infusion related reaction | 1/110 (0.9%) | 2/108 (1.9%) | ||
| Investigations | ||||
| Blood creatinine increased | 0/110 (0%) | 2/108 (1.9%) | ||
| International normalised ratio increased | 0/110 (0%) | 1/108 (0.9%) | ||
| Neutrophil count decreased | 1/110 (0.9%) | 0/108 (0%) | ||
| Transaminases increased | 1/110 (0.9%) | 0/108 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/110 (2.7%) | 0/108 (0%) | ||
| Hypercalcaemia | 2/110 (1.8%) | 2/108 (1.9%) | ||
| Hyperkalaemia | 0/110 (0%) | 1/108 (0.9%) | ||
| Hypokalaemia | 1/110 (0.9%) | 0/108 (0%) | ||
| Hypomagnesaemia | 1/110 (0.9%) | 0/108 (0%) | ||
| Tumour lysis syndrome | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/110 (0.9%) | 0/108 (0%) | ||
| Joint effusion | 0/110 (0%) | 1/108 (0.9%) | ||
| Myalgia | 0/110 (0%) | 1/108 (0.9%) | ||
| Pain in jaw | 1/110 (0.9%) | 0/108 (0%) | ||
| Pathological fracture | 0/110 (0%) | 1/108 (0.9%) | ||
| Rhabdomyolysis | 1/110 (0.9%) | 0/108 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Bronchial carcinoma | 1/110 (0.9%) | 0/108 (0%) | ||
| Laryngeal squamous cell carcinoma | 0/110 (0%) | 1/108 (0.9%) | ||
| Squamous cell carcinoma | 1/110 (0.9%) | 0/108 (0%) | ||
| Nervous system disorders | ||||
| Amnesia | 1/110 (0.9%) | 0/108 (0%) | ||
| Cerebrovascular accident | 1/110 (0.9%) | 0/108 (0%) | ||
| Convulsion | 1/110 (0.9%) | 0/108 (0%) | ||
| Headache | 0/110 (0%) | 1/108 (0.9%) | ||
| Iiird nerve disorder | 0/110 (0%) | 1/108 (0.9%) | ||
| Lethargy | 1/110 (0.9%) | 0/108 (0%) | ||
| Post herpetic neuralgia | 1/110 (0.9%) | 0/108 (0%) | ||
| Presyncope | 0/110 (0%) | 1/108 (0.9%) | ||
| Syncope | 0/110 (0%) | 1/108 (0.9%) | ||
| Transient ischaemic attack | 2/110 (1.8%) | 0/108 (0%) | ||
| Psychiatric disorders | ||||
| Agitation | 1/110 (0.9%) | 0/108 (0%) | ||
| Anxiety | 1/110 (0.9%) | 0/108 (0%) | ||
| Confusional state | 1/110 (0.9%) | 0/108 (0%) | ||
| Mental status changes | 0/110 (0%) | 1/108 (0.9%) | ||
| Renal and urinary disorders | ||||
| Pollakiuria | 0/110 (0%) | 1/108 (0.9%) | ||
| Renal failure acute | 1/110 (0.9%) | 0/108 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Chronic obstructive pulmonary disease | 1/110 (0.9%) | 1/108 (0.9%) | ||
| Cough | 0/110 (0%) | 1/108 (0.9%) | ||
| Dyspnoea | 2/110 (1.8%) | 3/108 (2.8%) | ||
| Haemoptysis | 1/110 (0.9%) | 0/108 (0%) | ||
| Hypoxia | 2/110 (1.8%) | 1/108 (0.9%) | ||
| Pleural effusion | 2/110 (1.8%) | 1/108 (0.9%) | ||
| Pneumonitis | 4/110 (3.6%) | 1/108 (0.9%) | ||
| Pulmonary embolism | 1/110 (0.9%) | 0/108 (0%) | ||
| Pulmonary mass | 1/110 (0.9%) | 0/108 (0%) | ||
| Pulmonary oedema | 0/110 (0%) | 2/108 (1.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 1/110 (0.9%) | 0/108 (0%) | ||
| Dermatitis exfoliative | 1/110 (0.9%) | 0/108 (0%) | ||
| Rash | 0/110 (0%) | 1/108 (0.9%) | ||
| Rash macular | 0/110 (0%) | 1/108 (0.9%) | ||
| Skin disorder | 1/110 (0.9%) | 0/108 (0%) | ||
| Urticaria | 1/110 (0.9%) | 0/108 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 2/110 (1.8%) | 0/108 (0%) | ||
| Embolism | 0/110 (0%) | 1/108 (0.9%) | ||
| Hypotension | 2/110 (1.8%) | 1/108 (0.9%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Idelalisib + Rituximab | Placebo + Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 103/110 (93.6%) | 102/108 (94.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 13/110 (11.8%) | 11/108 (10.2%) | ||
| Neutropenia | 28/110 (25.5%) | 21/108 (19.4%) | ||
| Thrombocytopenia | 8/110 (7.3%) | 4/108 (3.7%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 2/110 (1.8%) | 6/108 (5.6%) | ||
| Abdominal pain | 9/110 (8.2%) | 11/108 (10.2%) | ||
| Abdominal pain upper | 8/110 (7.3%) | 3/108 (2.8%) | ||
| Colitis | 6/110 (5.5%) | 1/108 (0.9%) | ||
| Constipation | 16/110 (14.5%) | 15/108 (13.9%) | ||
| Diarrhoea | 31/110 (28.2%) | 19/108 (17.6%) | ||
| Gastrooesophageal reflux disease | 11/110 (10%) | 0/108 (0%) | ||
| Nausea | 30/110 (27.3%) | 25/108 (23.1%) | ||
| Stomatitis | 7/110 (6.4%) | 1/108 (0.9%) | ||
| Vomiting | 16/110 (14.5%) | 9/108 (8.3%) | ||
| General disorders | ||||
| Asthenia | 8/110 (7.3%) | 8/108 (7.4%) | ||
| Chills | 27/110 (24.5%) | 16/108 (14.8%) | ||
| Fatigue | 34/110 (30.9%) | 35/108 (32.4%) | ||
| Oedema peripheral | 12/110 (10.9%) | 10/108 (9.3%) | ||
| Pain | 8/110 (7.3%) | 1/108 (0.9%) | ||
| Pyrexia | 40/110 (36.4%) | 18/108 (16.7%) | ||
| Infections and infestations | ||||
| Bronchitis | 7/110 (6.4%) | 4/108 (3.7%) | ||
| Cellulitis | 7/110 (6.4%) | 2/108 (1.9%) | ||
| Pneumonia | 4/110 (3.6%) | 6/108 (5.6%) | ||
| Sinusitis | 9/110 (8.2%) | 6/108 (5.6%) | ||
| Upper respiratory tract infection | 9/110 (8.2%) | 13/108 (12%) | ||
| Urinary tract infection | 8/110 (7.3%) | 4/108 (3.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 21/110 (19.1%) | 33/108 (30.6%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 8/110 (7.3%) | 0/108 (0%) | ||
| Aspartate aminotransferase increased | 8/110 (7.3%) | 0/108 (0%) | ||
| Weight decreased | 11/110 (10%) | 9/108 (8.3%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 18/110 (16.4%) | 12/108 (11.1%) | ||
| Hypokalaemia | 8/110 (7.3%) | 6/108 (5.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 9/110 (8.2%) | 4/108 (3.7%) | ||
| Back pain | 6/110 (5.5%) | 4/108 (3.7%) | ||
| Muscle spasms | 8/110 (7.3%) | 7/108 (6.5%) | ||
| Nervous system disorders | ||||
| Dizziness | 7/110 (6.4%) | 9/108 (8.3%) | ||
| Headache | 11/110 (10%) | 9/108 (8.3%) | ||
| Psychiatric disorders | ||||
| Anxiety | 3/110 (2.7%) | 7/108 (6.5%) | ||
| Insomnia | 10/110 (9.1%) | 7/108 (6.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 27/110 (24.5%) | 34/108 (31.5%) | ||
| Dyspnoea | 17/110 (15.5%) | 22/108 (20.4%) | ||
| Nasal congestion | 6/110 (5.5%) | 4/108 (3.7%) | ||
| Oropharyngeal pain | 6/110 (5.5%) | 6/108 (5.6%) | ||
| Productive cough | 6/110 (5.5%) | 4/108 (3.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Night sweats | 12/110 (10.9%) | 13/108 (12%) | ||
| Pruritus | 6/110 (5.5%) | 5/108 (4.6%) | ||
| Rash | 16/110 (14.5%) | 4/108 (3.7%) | ||
| Skin lesion | 3/110 (2.7%) | 7/108 (6.5%) | ||
| Vascular disorders | ||||
| Hypotension | 4/110 (3.6%) | 7/108 (6.5%) | ||
Limitations/Caveats
Following a recommendation by an independent Data Monitoring Committee (DMC), the study was stopped early due to highly statistically significant results for the primary efficacy endpoint of progression-free survival.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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, Inc. |
| Phone | |
| ClinicalTrialDisclosures@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01539512
Other Study ID Numbers:
- GS-US-312-0116
- 2011-005180-24
First Posted:
Feb 27, 2012
Last Update Posted:
May 14, 2019
Last Verified:
Apr 1, 2015