Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01569295

Collaborator

(none)

416

Enrollment

106

Locations

Arms

83.8

Actual Duration (Months)

3.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the effect of the addition of idelalisib (formerly GS-1101) to bendamustine + rituximab (BR) on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL)

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Idelalisib Drug: Rituximab Drug: Bendamustine Drug: Placebo to match idelalisib	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

416 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 Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia

Actual Study Start Date :

Jun 15, 2012

Actual Primary Completion Date :

Jun 10, 2019

Actual Study Completion Date :

Jun 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Idelalisib+bendamustine+rituximab Participants will receive idelalisib plus bendamustine and rituximab	Drug: Idelalisib Idelalisib 150 mg administered orally twice daily Other Names: GS-1101 CAL-101 Zydelig® Drug: Rituximab Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions Other Names: Rituxan® MabThera Drug: Bendamustine Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions Other Names: Ribomustin Treanda®
Placebo Comparator: Placebo to match idelalisib+bendamustine+rituximab Participants will receive placebo to match idelalisib plus bendamustine and rituximab	Drug: Rituximab Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions Other Names: Rituxan® MabThera Drug: Bendamustine Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions Other Names: Ribomustin Treanda® Drug: Placebo to match idelalisib Placebo to match idelalisib administered orally twice daily

Arm

Intervention/Treatment

Experimental: Idelalisib+bendamustine+rituximab

Participants will receive idelalisib plus bendamustine and rituximab

Drug: Idelalisib

Idelalisib 150 mg administered orally twice daily

Other Names:

GS-1101

CAL-101

Zydelig®

Drug: Rituximab

Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions

Other Names:

Rituxan®

MabThera

Drug: Bendamustine

Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions

Other Names:

Ribomustin

Treanda®

Placebo Comparator: Placebo to match idelalisib+bendamustine+rituximab

Participants will receive placebo to match idelalisib plus bendamustine and rituximab

Drug: Rituximab

Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions

Other Names:

Rituxan®

MabThera

Drug: Bendamustine

Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions

Other Names:

Ribomustin

Treanda®

Drug: Placebo to match idelalisib

Placebo to match idelalisib administered orally twice daily

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) [Up to 84 months]
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.

Secondary Outcome Measures

Overall Response Rate (ORR) [Up to 84 months]
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.
Lymph Node Response Rate [Up to 84 months]
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.
Overall Survival [Up to 84 months]
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.
Complete Response Rate [Up to 84 months]
Complete response (CR) rate was defined as the percentage of participants who achieved a CR.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Previously treated recurrent CLL
Measurable lymphadenopathy
Requires therapy for CLL
Has experienced CLL progression < 36 months since the completion of the last prior therapy

Key Exclusion Criteria:

Recent history of a major non-CLL malignancy
Evidence of an ongoing infection
CLL refractory to bendamustine
Concurrent participation in another therapeutic clinical trial

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clearview Cancer Institute	Huntsville	Alabama	United States	35805
2	UCLA Medical Center	Los Angeles	California	United States	90095
3	Stanford Cancer Center	Palo Alto	California	United States	94035
4	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
5	University of Florida	Gainesville	Florida	United States	32603
6	Winship Cancer Institute at Emory University	Atlanta	Georgia	United States	30322
7	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
8	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
9	Summit Medical Group, P.A.	Morristown	New Jersey	United States	07962
10	North Shore University Hospital	Manhasset	New York	United States	11030
11	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11042
12	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
13	Columbia University Medical Center	New York	New York	United States	10032
14	Willamette Valley Cancer Center	Eugene	Oregon	United States	97477
15	Charleston Hematology Oncology	Charleston	South Carolina	United States	29414
16	Texas Oncology	Austin	Texas	United States	78731
17	Texas Oncology PA	Dallas	Texas	United States	75246
18	Texas Oncology	Fort Worth	Texas	United States	76104
19	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
20	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
21	Cancer Care Northwest, US Oncology	Spokane	Washington	United States	99202
22	Virginia Cancer Specialists, PC	Vancouver	Washington	United States	98684
23	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
24	St Vincent's Hospital - Sydney	Darlinghurst	New South Wales	Australia	2010
25	Gosford Hospital	Gosford	New South Wales	Australia	2250
26	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
27	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
28	Monash Medical Centre - Clayton Campus	Clayton	Victoria	Australia	3168
29	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
30	Princess Alexandra Hospital	Woolloongabba		Australia	4102
31	Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg	Antwerpen		Belgium	2060
32	UZ Gent	Gent		Belgium	9000
33	UZ Leuven	Leuven		Belgium	3000
34	Cancer Care Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
35	Clinical Hospital "Dubrava"	Zagreb		Croatia	10000
36	Klinichki Bolnicki Centar-Zagreb	Zagreb		Croatia	10000
37	University Hospital Merkur	Zagreb		Croatia	10000
38	Fakultni nemocnice Brno	Brno		Czechia	625 00
39	Fakultní nemocnice Hradec Králové	Hradec Králové		Czechia	500 05
40	Fakultni nemocnice Ostrava	Ostrava		Czechia	708 52
41	Hopital Henri Mondor	Créteil		France	94010
42	Centre Jean Bernard - Clinique Victor Hugo	Le Mans cedex		France	72015
43	CHRU Lille-Hôpital Claude Huriez	Lille		France	59045
44	Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes	Lyon		France	69373
45	Centre Hospitalier de Mulhouse	Mulhouse		France	68100
46	CHU Hôtel-Dieu-Service Hématologie	Nantes		France	44 093
47	Centre Hospitalier Lyon Sud	Pierre Bénite		France	Pierre Bénite
48	Hopital Purpan	Toulouse		France	31059
49	Hôpitaux de Brabois	Vandoeuvre-lés-Nancy		France	54511
50	G. Genimatas Hospital	Athens		Greece	11527
51	University General Hospital of Patras	Patras		Greece	26500
52	Semmelweis Egyetem	Budapest		Hungary	1083
53	Országos Onkológiai Intézet	Budapest		Hungary	1122
54	Debreceni Egyetem Orvos- és Egészségtudományi Centrum	Debrecen		Hungary	4032
55	Tallian Gyula utca 20-32	Kaposvár		Hungary	7400
56	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ	Szeged		Hungary	6720
57	Mater Misericordiae Hospital	Dublin		Ireland
58	Spedali Civili di Brescia	Brescia		Italy	25123
59	Ospedale Oncologico Regionale A. Businco	Cagliari		Italy	9121
60	IRCCS Ospedale San Raffaele	Milano		Italy	20132
61	Azienda Ospedaliera Universitaria San Giovanni Battista-Molinette	Torino		Italy	10126
62	Szpital Specjalistyczny w Brzozowie	Brzozow		Poland	36-200
63	Malopolskie Centrum Medyczne	Krakow		Poland	30-510
64	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi	Lodz		Poland	93-510
65	Samodzielny Publiczny Szpital Kliniczny Nr 1	Lublin		Poland	20-081
66	Wojewodzki Szpital w Opolu	Opole		Poland	43-372
67	Centralny Szpital Kliniczny MSW w Warszawie	Warszawa		Poland	02-507
68	Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie	Warszawa		Poland	02-781
69	Hospital Santa Maria	Lisboa		Portugal	1649-035
70	"Instituto Portugues de Oncologia do Porto Francisco Gentil (IPOPFG, EPE)	Porto		Portugal	4200-072
71	Emergency County Clinical Hospital Brasov	Brasov		Romania	500152
72	"Colentina" Clinical Hospital	Bucharest		Romania	20125
73	"Fundeni" Clinical Institute	Bucharest		Romania	22328
74	Regional Oncology Institute Iasi	Iasi		Romania	700483
75	Russian Oncology Research Center (N.N. Blokhin)	Moscow		Russian Federation	115478
76	Nizhegorodskaya Regional Clinical Hospital n.a. N.A. Semashko	Nizhniy Novgorod		Russian Federation	603126
77	Novosibirsk State Regional Clinical Hospital	Novosibirsk		Russian Federation
78	Ryazan Regional Clinical Hospital	Ryazan		Russian Federation	390039
79	Saratov State Medical University	Saratov		Russian Federation	410028
80	Research Institute of Hematology and Blood Transfusion	St. Petersburg		Russian Federation	193024
81	State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary #1	Volgograd		Russian Federation	400138
82	Hospital Universitario Germans Trias i Pujol	Badalona	Cataluña	Spain	08916
83	Hospital Clinic de Barcelona	Barcelona	Cataluña	Spain	8036
84	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña	Spain	8041
85	Hospital 12 de Octubre	Madrid	Madrid, Communidad De	Spain	28041
86	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid, Communidad De	Spain	28222
87	Hospital Universitario de La Princesa	Madrid		Spain	28033
88	Gazi University Medical Faculty Gazi Hospital	Ankara		Turkey	06500
89	Ankara University Medical Faculty	Ankara		Turkey	6590
90	Istanbul University Istanbul Medical Faculty	Istanbul		Turkey	34093
91	Ondokuz Mayis University Faculty of Medicine	Samsun		Turkey	55239
92	Birmingham Heartlands Hospital	Birmingham		United Kingdom	B9 5SS
93	Kent and Canterbury Hospital	Canterbury		United Kingdom	CT1 3NG
94	University Hospital of Wales	Cardiff		United Kingdom	CF14 4XW
95	Dorset County Hospital	Dorchester		United Kingdom	DT1 2JY
96	St. James University Hospital	Leeds		United Kingdom	LS9 7TF
97	Royal Liverpool University Hospital	Liverpool		United Kingdom	L7 8XP
98	St Bartholomews Hospital	London		United Kingdom	EC1A 7BE
99	King's College Hospital	London		United Kingdom	SE5 9RS
100	Hammersmith Hospital	London		United Kingdom	W12 0NN
101	University College London	London		United Kingdom	WC1E 6BT
102	Christie Hospital	Manchester		United Kingdom	M20 4BX
103	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom	NG5 1PB
104	Churchill Hospital	Oxford		United Kingdom	OX3 7LE
105	Royal Cornwall Hospital	Truro		United Kingdom	TR1 3LJ
106	New Cross Hospital	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

More Information

Publications

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01569295

Other Study ID Numbers:

GS-US-312-0115
2011-006292-20

First Posted:

Apr 3, 2012

Last Update Posted:

Mar 10, 2020

Last Verified:

Mar 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Gilead Sciences

Additional relevant MeSH terms:

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Rituximab

Bendamustine Hydrochloride

Idelalisib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 110 sites in Australia, New Zealand, Europe, Asia and North America. The first participant was screened on 15 June 2012. The last study visit occurred on 10 June 2019.
Pre-assignment Detail	540 participants were screened.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab
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
Long-Term Follow-up	109	161
COMPLETED	0	0
NOT COMPLETED	207	209

Baseline Characteristics

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab	Total
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 Participants	207	209	416
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (9.2)	63 (9.8)	62 (9.5)
Sex: Female, Male (Count of Participants)
Female	47 22.7%	53 25.4%	100 24%
Male	160 77.3%	156 74.6%	316 76%
Race/Ethnicity, Customized (Count of 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%	1 0.5%	3 0.7%
Other	2 1%	2 1%	4 1%
Not Permitted	10 4.8%	12 5.7%	22 5.3%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	4 1.9%	5 2.4%	9 2.2%
Not Hispanic or Latino	191 92.3%	188 90%	379 91.1%
Not Permitted	12 5.8%	15 7.2%	27 6.5%
Missing	0 0%	1 0.5%	1 0.2%
Region of Enrollment (Count of 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%	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%	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%	6 1.4%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	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 84 months

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) Analysis Set included all participants randomised in the study regardless of whether study drug was administered and with treatment group designated according to initial randomisation.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab
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).
Measure Participants	207	209
Median (95% Confidence Interval) [months]	21.8	11.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Stratified log-rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95% 0.27 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio is estimated using Cox proportional hazard model, adjusted for randomization stratification factors.

2. Secondary Outcome

Title	Overall Response Rate (ORR)
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 84 months

Outcome Measure Data

Analysis Population Description
Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab
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).
Measure Participants	207	209
Number (95% Confidence Interval) [percentage of participants]	70.0 33.8%	45.5 21.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Odds ratio,p-value and 95% Confidence Interval(CI) were calculated from Cochran-Mantel-Haenszel(CMH) Chi-square test stratified by stratification factor in EDC(del17p/TP53,immunoglobulin heavy chain variable region(IgHV) mutation and disease status).
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.02
	Confidence Interval	(2-Sided) 95% 1.98 to 4.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

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 sum of the products of the greatest perpendicular diameters (SPD) of index lesions.
Time Frame	Up to 84 months

Outcome Measure Data

Analysis Population Description
Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab
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).
Measure Participants	192	197
Number (95% Confidence Interval) [percentage of particpants]	96.9	60.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Odds ratio, p-value and 95% CI 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

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	28.81
	Confidence Interval	(2-Sided) 95% 10.50 to 79.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Overall Survival
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 84 months

Outcome Measure Data

Analysis Population Description
Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab
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).
Measure Participants	207	209
Median (95% Confidence Interval) [months]	56.2	42.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	Stratified log-rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95% 0.59 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Complete Response Rate
Description	Complete response (CR) rate was defined as the percentage of participants who achieved a CR.
Time Frame	Up to 84 months

Outcome Measure Data

Analysis Population Description
Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab	Placebo + Bendamustine + Rituximab
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).
Measure Participants	207	209
Number (95% Confidence Interval) [percentage of participants]	4.3 2.1%	0.5 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Idelalisib + Bendamustine + Rituximab, Placebo + Bendamustine + Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments	Odds ratio, 95% CI and p-value are 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

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.55
	Confidence Interval	(2-Sided) 95% 1.19 to 76.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Idelalisib + Bendamustine + Rituximab		Placebo + Bendamustine + Rituximab
Time Frame	First dose up to the last dose date plus 30 days (Up to approximately 67.7 months)
Adverse Event Reporting Description	The Safety Analysis Set included all participants who received >=1 dose of study treatment, with treatment group assignments designated according to the actual treatment received.

Arm/Group Title	Idelalisib + Bendamustine + Rituximab		Placebo + Bendamustine + Rituximab
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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/207 (43%)		106/209 (50.7%)
Serious Adverse Events
	Idelalisib + Bendamustine + Rituximab		Placebo + Bendamustine + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	152/207 (73.4%)		94/209 (45%)
Blood and lymphatic system disorders
Agranulocytosis	0/207 (0%)		2/209 (1%)
Anaemia	8/207 (3.9%)		5/209 (2.4%)
Autoimmune haemolytic anaemia	0/207 (0%)		2/209 (1%)
Febrile neutropenia	45/207 (21.7%)		10/209 (4.8%)
Haemolytic anaemia	0/207 (0%)		1/209 (0.5%)
Immune thrombocytopenic purpura	1/207 (0.5%)		1/209 (0.5%)
Lymphadenopathy	0/207 (0%)		1/209 (0.5%)
Neutropenia	9/207 (4.3%)		3/209 (1.4%)
Pancytopenia	1/207 (0.5%)		0/209 (0%)
Thrombocytopenia	4/207 (1.9%)		0/209 (0%)
Thrombotic thrombocytopenic purpura	0/207 (0%)		1/209 (0.5%)
Cardiac disorders
Acute myocardial infarction	0/207 (0%)		2/209 (1%)
Angina pectoris	1/207 (0.5%)		0/209 (0%)
Atrial fibrillation	1/207 (0.5%)		1/209 (0.5%)
Cardiac arrest	1/207 (0.5%)		1/209 (0.5%)
Cardiac failure	0/207 (0%)		1/209 (0.5%)
Cardiac failure congestive	1/207 (0.5%)		0/209 (0%)
Left ventricular dysfunction	1/207 (0.5%)		0/209 (0%)
Pericardial effusion	1/207 (0.5%)		0/209 (0%)
Supraventricular extrasystoles	1/207 (0.5%)		0/209 (0%)
Eye disorders
Rhegmatogenous retinal detachment	1/207 (0.5%)		0/209 (0%)
Vision blurred	0/207 (0%)		1/209 (0.5%)
Gastrointestinal disorders
Abdominal hernia	1/207 (0.5%)		0/209 (0%)
Abdominal pain	4/207 (1.9%)		2/209 (1%)
Ascites	0/207 (0%)		2/209 (1%)
Colitis	5/207 (2.4%)		1/209 (0.5%)
Colitis microscopic	1/207 (0.5%)		0/209 (0%)
Colitis ulcerative	1/207 (0.5%)		0/209 (0%)
Constipation	1/207 (0.5%)		0/209 (0%)
Diarrhoea	14/207 (6.8%)		1/209 (0.5%)
Enterovesical fistula	1/207 (0.5%)		0/209 (0%)
Gastric haemorrhage	1/207 (0.5%)		1/209 (0.5%)
Gastrointestinal haemorrhage	1/207 (0.5%)		0/209 (0%)
Intestinal perforation	1/207 (0.5%)		0/209 (0%)
Nausea	1/207 (0.5%)		2/209 (1%)
Neutropenic colitis	0/207 (0%)		1/209 (0.5%)
Pancreatitis	2/207 (1%)		0/209 (0%)
Pancreatitis acute	1/207 (0.5%)		0/209 (0%)
Pneumatosis intestinalis	1/207 (0.5%)		0/209 (0%)
Pneumoperitoneum	1/207 (0.5%)		0/209 (0%)
Vomiting	0/207 (0%)		2/209 (1%)
General disorders
Asthenia	1/207 (0.5%)		2/209 (1%)
Chest pain	0/207 (0%)		1/209 (0.5%)
Chills	2/207 (1%)		0/209 (0%)
Fatigue	2/207 (1%)		2/209 (1%)
General physical health deterioration	1/207 (0.5%)		1/209 (0.5%)
Malaise	1/207 (0.5%)		0/209 (0%)
Multiple organ dysfunction syndrome	1/207 (0.5%)		1/209 (0.5%)
Pyrexia	25/207 (12.1%)		11/209 (5.3%)
Hepatobiliary disorders
Bile duct obstruction	0/207 (0%)		1/209 (0.5%)
Biliary fistula	1/207 (0.5%)		0/209 (0%)
Cholangitis	0/207 (0%)		1/209 (0.5%)
Cholecystitis	1/207 (0.5%)		0/209 (0%)
Cholelithiasis	1/207 (0.5%)		0/209 (0%)
Hepatic failure	0/207 (0%)		1/209 (0.5%)
Hepatitis toxic	1/207 (0.5%)		0/209 (0%)
Hepatocellular injury	2/207 (1%)		0/209 (0%)
Hepatotoxicity	0/207 (0%)		1/209 (0.5%)
Immune system disorders
Drug hypersensitivity	1/207 (0.5%)		0/209 (0%)
Haemophagocytic lymphohistiocytosis	0/207 (0%)		1/209 (0.5%)
Hypersensitivity	2/207 (1%)		0/209 (0%)
Infections and infestations
Aspergillus infection	0/207 (0%)		1/209 (0.5%)
Bacteraemia	0/207 (0%)		1/209 (0.5%)
Bacterial sepsis	1/207 (0.5%)		0/209 (0%)
Brain abscess	0/207 (0%)		1/209 (0.5%)
Bronchitis	1/207 (0.5%)		5/209 (2.4%)
Bronchopulmonary aspergillosis	1/207 (0.5%)		0/209 (0%)
Campylobacter gastroenteritis	1/207 (0.5%)		0/209 (0%)
Cellulitis	4/207 (1.9%)		0/209 (0%)
Clostridium difficile infection	0/207 (0%)		1/209 (0.5%)
Conjunctivitis bacterial	1/207 (0.5%)		0/209 (0%)
Cystitis	1/207 (0.5%)		0/209 (0%)
Cytomegalovirus chorioretinitis	1/207 (0.5%)		1/209 (0.5%)
Cytomegalovirus colitis	1/207 (0.5%)		0/209 (0%)
Cytomegalovirus enteritis	1/207 (0.5%)		0/209 (0%)
Cytomegalovirus infection	3/207 (1.4%)		1/209 (0.5%)
Cytomegalovirus viraemia	1/207 (0.5%)		0/209 (0%)
Device related infection	2/207 (1%)		1/209 (0.5%)
Diverticulitis	1/207 (0.5%)		0/209 (0%)
Ecthyma	1/207 (0.5%)		0/209 (0%)
Escherichia bacteraemia	1/207 (0.5%)		0/209 (0%)
Escherichia sepsis	2/207 (1%)		0/209 (0%)
Eye infection toxoplasmal	1/207 (0.5%)		0/209 (0%)
Fungal infection	0/207 (0%)		1/209 (0.5%)
Gastroenteritis	2/207 (1%)		0/209 (0%)
Gastroenteritis cryptosporidial	1/207 (0.5%)		0/209 (0%)
H1n1 influenza	1/207 (0.5%)		0/209 (0%)
Haemophilus infection	1/207 (0.5%)		0/209 (0%)
Herpes simplex	1/207 (0.5%)		0/209 (0%)
Herpes zoster	4/207 (1.9%)		1/209 (0.5%)
Human herpesvirus 6 infection	0/207 (0%)		1/209 (0.5%)
Impetigo	0/207 (0%)		1/209 (0.5%)
Influenza	3/207 (1.4%)		1/209 (0.5%)
Lower respiratory tract infection	7/207 (3.4%)		5/209 (2.4%)
Lower respiratory tract infection fungal	1/207 (0.5%)		0/209 (0%)
Lung infection	0/207 (0%)		3/209 (1.4%)
Meningitis aseptic	1/207 (0.5%)		0/209 (0%)
Meningitis bacterial	0/207 (0%)		1/209 (0.5%)
Meningitis enteroviral	1/207 (0.5%)		0/209 (0%)
Neutropenic infection	1/207 (0.5%)		0/209 (0%)
Neutropenic sepsis	3/207 (1.4%)		6/209 (2.9%)
Ophthalmic herpes zoster	2/207 (1%)		0/209 (0%)
Oral herpes	1/207 (0.5%)		0/209 (0%)
Oropharyngitis fungal	1/207 (0.5%)		0/209 (0%)
Otitis externa	1/207 (0.5%)		0/209 (0%)
Otitis media	0/207 (0%)		2/209 (1%)
Perineal infection	1/207 (0.5%)		0/209 (0%)
Pharyngeal abscess	0/207 (0%)		1/209 (0.5%)
Pneumocystis jirovecii infection	1/207 (0.5%)		0/209 (0%)
Pneumocystis jirovecii pneumonia	3/207 (1.4%)		0/209 (0%)
Pneumonia	38/207 (18.4%)		16/209 (7.7%)
Pneumonia bacterial	0/207 (0%)		1/209 (0.5%)
Pneumonia cytomegaloviral	1/207 (0.5%)		1/209 (0.5%)
Pneumonia pseudomonal	2/207 (1%)		0/209 (0%)
Pneumonia viral	0/207 (0%)		1/209 (0.5%)
Pulmonary mycosis	0/207 (0%)		1/209 (0.5%)
Pulmonary sepsis	1/207 (0.5%)		0/209 (0%)
Respiratory syncytial virus infection	1/207 (0.5%)		0/209 (0%)
Respiratory tract infection	5/207 (2.4%)		5/209 (2.4%)
Rhinovirus infection	1/207 (0.5%)		0/209 (0%)
Sepsis	11/207 (5.3%)		4/209 (1.9%)
Septic shock	5/207 (2.4%)		1/209 (0.5%)
Sinusitis	2/207 (1%)		0/209 (0%)
Skin infection	1/207 (0.5%)		0/209 (0%)
Soft tissue infection	1/207 (0.5%)		0/209 (0%)
Tonsillitis	1/207 (0.5%)		0/209 (0%)
Tuberculosis	1/207 (0.5%)		0/209 (0%)
Upper respiratory tract infection	1/207 (0.5%)		4/209 (1.9%)
Upper respiratory tract infection bacterial	1/207 (0.5%)		0/209 (0%)
Urinary tract infection	7/207 (3.4%)		3/209 (1.4%)
Urinary tract infection bacterial	0/207 (0%)		1/209 (0.5%)
Urosepsis	2/207 (1%)		1/209 (0.5%)
Viral infection	0/207 (0%)		1/209 (0.5%)
Injury, poisoning and procedural complications
Ankle fracture	1/207 (0.5%)		0/209 (0%)
Cervical vertebral fracture	1/207 (0.5%)		0/209 (0%)
Eye injury	0/207 (0%)		1/209 (0.5%)
Femur fracture	1/207 (0.5%)		1/209 (0.5%)
Infusion related reaction	1/207 (0.5%)		3/209 (1.4%)
Periprosthetic fracture	1/207 (0.5%)		0/209 (0%)
Wrist fracture	1/207 (0.5%)		0/209 (0%)
Investigations
Alanine aminotransferase increased	1/207 (0.5%)		0/209 (0%)
Anticoagulation drug level above therapeutic	1/207 (0.5%)		0/209 (0%)
Aspartate aminotransferase increased	1/207 (0.5%)		0/209 (0%)
Bk polyomavirus test positive	1/207 (0.5%)		0/209 (0%)
Blood creatinine increased	1/207 (0.5%)		0/209 (0%)
Blood lactate dehydrogenase increased	0/207 (0%)		1/209 (0.5%)
Neutrophil count decreased	1/207 (0.5%)		0/209 (0%)
Streptococcus test positive	1/207 (0.5%)		0/209 (0%)
Transaminases increased	1/207 (0.5%)		0/209 (0%)
Metabolism and nutrition disorders
Cachexia	1/207 (0.5%)		0/209 (0%)
Decreased appetite	1/207 (0.5%)		0/209 (0%)
Dehydration	1/207 (0.5%)		1/209 (0.5%)
Diabetes mellitus inadequate control	1/207 (0.5%)		0/209 (0%)
Hypercalcaemia	0/207 (0%)		1/209 (0.5%)
Hyperglycaemia	1/207 (0.5%)		0/209 (0%)
Hypoalbuminaemia	1/207 (0.5%)		0/209 (0%)
Hypokalaemia	1/207 (0.5%)		1/209 (0.5%)
Hyponatraemia	2/207 (1%)		0/209 (0%)
Hypovolaemia	1/207 (0.5%)		0/209 (0%)
Malnutrition	1/207 (0.5%)		0/209 (0%)
Tumour lysis syndrome	3/207 (1.4%)		2/209 (1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/207 (0.5%)		0/209 (0%)
Chondritis	1/207 (0.5%)		0/209 (0%)
Chondrocalcinosis	1/207 (0.5%)		0/209 (0%)
Myalgia	1/207 (0.5%)		0/209 (0%)
Polyarthritis	1/207 (0.5%)		0/209 (0%)
Reiter's syndrome	1/207 (0.5%)		0/209 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	1/207 (0.5%)		0/209 (0%)
Adenocarcinoma of colon	0/207 (0%)		2/209 (1%)
Basal cell carcinoma	3/207 (1.4%)		0/209 (0%)
Bladder cancer	1/207 (0.5%)		0/209 (0%)
Bowen's disease	1/207 (0.5%)		0/209 (0%)
Chronic lymphocytic leukaemia	1/207 (0.5%)		0/209 (0%)
Gastric cancer	0/207 (0%)		1/209 (0.5%)
Leiomyosarcoma	1/207 (0.5%)		0/209 (0%)
Lip squamous cell carcinoma	1/207 (0.5%)		0/209 (0%)
Lung adenocarcinoma	1/207 (0.5%)		1/209 (0.5%)
Lung neoplasm malignant	1/207 (0.5%)		0/209 (0%)
Malignant melanoma	2/207 (1%)		0/209 (0%)
Meningioma	1/207 (0.5%)		0/209 (0%)
Metastases to bone	1/207 (0.5%)		0/209 (0%)
Myelodysplastic syndrome	4/207 (1.9%)		0/209 (0%)
Nasopharyngeal cancer	0/207 (0%)		1/209 (0.5%)
Oesophageal carcinoma	1/207 (0.5%)		0/209 (0%)
Prostate cancer	2/207 (1%)		0/209 (0%)
Rectal adenocarcinoma	1/207 (0.5%)		0/209 (0%)
Salivary gland neoplasm	1/207 (0.5%)		0/209 (0%)
Squamous cell carcinoma	1/207 (0.5%)		5/209 (2.4%)
Squamous cell carcinoma of lung	1/207 (0.5%)		0/209 (0%)
Squamous cell carcinoma of skin	3/207 (1.4%)		2/209 (1%)
T-cell lymphoma	0/207 (0%)		1/209 (0.5%)
Transitional cell carcinoma	1/207 (0.5%)		0/209 (0%)
Nervous system disorders
Cerebral haemorrhage	1/207 (0.5%)		0/209 (0%)
Dizziness	1/207 (0.5%)		0/209 (0%)
Headache	0/207 (0%)		1/209 (0.5%)
Ischaemic stroke	1/207 (0.5%)		0/209 (0%)
Post herpetic neuralgia	0/207 (0%)		1/209 (0.5%)
Seizure	1/207 (0.5%)		0/209 (0%)
Syncope	1/207 (0.5%)		0/209 (0%)
Psychiatric disorders
Anxiety	0/207 (0%)		1/209 (0.5%)
Confusional state	1/207 (0.5%)		0/209 (0%)
Delusion	1/207 (0.5%)		0/209 (0%)
Mental status changes	0/207 (0%)		1/209 (0.5%)
Mood swings	1/207 (0.5%)		0/209 (0%)
Panic attack	1/207 (0.5%)		0/209 (0%)
Personality change	1/207 (0.5%)		0/209 (0%)
Renal and urinary disorders
Acute kidney injury	1/207 (0.5%)		1/209 (0.5%)
Calculus urinary	0/207 (0%)		1/209 (0.5%)
Haematuria	1/207 (0.5%)		0/209 (0%)
Renal colic	2/207 (1%)		0/209 (0%)
Renal failure	0/207 (0%)		1/209 (0.5%)
Urinary incontinence	1/207 (0.5%)		0/209 (0%)
Reproductive system and breast disorders
Cervical polyp	1/207 (0.5%)		0/209 (0%)
Perineal necrosis	1/207 (0.5%)		0/209 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/207 (0%)		1/209 (0.5%)
Bronchial hyperreactivity	1/207 (0.5%)		0/209 (0%)
Chronic obstructive pulmonary disease	0/207 (0%)		1/209 (0.5%)
Cough	4/207 (1.9%)		2/209 (1%)
Dyspnoea	4/207 (1.9%)		3/209 (1.4%)
Epistaxis	0/207 (0%)		1/209 (0.5%)
Hypoxia	2/207 (1%)		0/209 (0%)
Lung disorder	0/207 (0%)		1/209 (0.5%)
Pleural effusion	3/207 (1.4%)		0/209 (0%)
Pneumonia aspiration	1/207 (0.5%)		0/209 (0%)
Pneumonitis	4/207 (1.9%)		0/209 (0%)
Pneumothorax	0/207 (0%)		1/209 (0.5%)
Pulmonary embolism	2/207 (1%)		5/209 (2.4%)
Pulmonary pain	0/207 (0%)		1/209 (0.5%)
Respiratory distress	1/207 (0.5%)		0/209 (0%)
Respiratory failure	2/207 (1%)		0/209 (0%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	1/207 (0.5%)		0/209 (0%)
Dermatitis exfoliative	1/207 (0.5%)		0/209 (0%)
Dermatitis exfoliative generalised	1/207 (0.5%)		0/209 (0%)
Drug reaction with eosinophilia and systemic symptoms	1/207 (0.5%)		0/209 (0%)
Rash macular	1/207 (0.5%)		0/209 (0%)
Rash maculo-papular	1/207 (0.5%)		0/209 (0%)
Stevens-Johnson syndrome	2/207 (1%)		0/209 (0%)
Vascular disorders
Deep vein thrombosis	1/207 (0.5%)		0/209 (0%)
Hypotension	2/207 (1%)		2/209 (1%)
Other (Not Including Serious) Adverse Events
	Idelalisib + Bendamustine + Rituximab		Placebo + Bendamustine + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	199/207 (96.1%)		196/209 (93.8%)
Blood and lymphatic system disorders
Anaemia	54/207 (26.1%)		48/209 (23%)
Leukopenia	17/207 (8.2%)		10/209 (4.8%)
Neutropenia	129/207 (62.3%)		113/209 (54.1%)
Thrombocytopenia	41/207 (19.8%)		46/209 (22%)
Gastrointestinal disorders
Abdominal pain	21/207 (10.1%)		13/209 (6.2%)
Constipation	32/207 (15.5%)		35/209 (16.7%)
Diarrhoea	89/207 (43%)		47/209 (22.5%)
Dyspepsia	15/207 (7.2%)		8/209 (3.8%)
Nausea	60/207 (29%)		72/209 (34.4%)
Vomiting	35/207 (16.9%)		31/209 (14.8%)
General disorders
Asthenia	24/207 (11.6%)		20/209 (9.6%)
Chills	22/207 (10.6%)		13/209 (6.2%)
Fatigue	45/207 (21.7%)		52/209 (24.9%)
Oedema peripheral	17/207 (8.2%)		18/209 (8.6%)
Pyrexia	78/207 (37.7%)		55/209 (26.3%)
Immune system disorders
Hypogammaglobulinaemia	12/207 (5.8%)		10/209 (4.8%)
Infections and infestations
Bronchitis	20/207 (9.7%)		8/209 (3.8%)
Herpes zoster	11/207 (5.3%)		6/209 (2.9%)
Lower respiratory tract infection	13/207 (6.3%)		10/209 (4.8%)
Nasopharyngitis	16/207 (7.7%)		11/209 (5.3%)
Pneumonia	25/207 (12.1%)		13/209 (6.2%)
Respiratory tract infection	7/207 (3.4%)		11/209 (5.3%)
Sinusitis	19/207 (9.2%)		13/209 (6.2%)
Upper respiratory tract infection	37/207 (17.9%)		21/209 (10%)
Injury, poisoning and procedural complications
Infusion related reaction	29/207 (14%)		45/209 (21.5%)
Investigations
Alanine aminotransferase increased	32/207 (15.5%)		2/209 (1%)
Aspartate aminotransferase increased	19/207 (9.2%)		2/209 (1%)
Weight decreased	25/207 (12.1%)		12/209 (5.7%)
Metabolism and nutrition disorders
Decreased appetite	24/207 (11.6%)		15/209 (7.2%)
Hypokalaemia	21/207 (10.1%)		16/209 (7.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	27/207 (13%)		16/209 (7.7%)
Back pain	17/207 (8.2%)		15/209 (7.2%)
Nervous system disorders
Headache	20/207 (9.7%)		21/209 (10%)
Psychiatric disorders
Anxiety	6/207 (2.9%)		12/209 (5.7%)
Insomnia	19/207 (9.2%)		13/209 (6.2%)
Respiratory, thoracic and mediastinal disorders
Cough	52/207 (25.1%)		47/209 (22.5%)
Dyspnoea	20/207 (9.7%)		26/209 (12.4%)
Oropharyngeal pain	10/207 (4.8%)		14/209 (6.7%)
Productive cough	17/207 (8.2%)		12/209 (5.7%)
Skin and subcutaneous tissue disorders
Night sweats	18/207 (8.7%)		8/209 (3.8%)
Pruritus	17/207 (8.2%)		12/209 (5.7%)
Rash	36/207 (17.4%)		28/209 (13.4%)
Vascular disorders
Hypertension	13/207 (6.3%)		5/209 (2.4%)
Hypotension	14/207 (6.8%)		13/209 (6.2%)

Limitations/Caveats

[Not Specified]

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	Gilead Clinical Study Information Center
Organization	Gilead Sciences
Phone	1-833-445-3230 (GILEAD-0)
Email	ClinicalTrialDisclosures@gilead.com

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01569295

Other Study ID Numbers:

GS-US-312-0115
2011-006292-20

First Posted:

Apr 3, 2012

Last Update Posted:

Mar 10, 2020

Last Verified:

Mar 1, 2020

Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Key Inclusion Criteria:

Key Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact