History of Changes for Study: NCT01569295

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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Study Record Versions

Version	Submitted Date	Changes
1	March 30, 2012	None (earliest Version on record)
2	May 31, 2012	Recruitment Status, Study Status, Outcome Measures, Contacts/Locations and Oversight
3	June 18, 2012	Study Status
4	July 18, 2012	Study Status and Contacts/Locations
5	August 29, 2012	Study Status and Contacts/Locations
6	September 15, 2012	Study Status and Contacts/Locations
7	November 12, 2012	Contacts/Locations and Study Status
8	November 28, 2012	Contacts/Locations and Study Status
9	January 12, 2013	Arms and Interventions, Contacts/Locations, Study Description, Study Status, Study Identification and Conditions
10	March 11, 2013	Contacts/Locations and Study Status
11	March 18, 2013	Contacts/Locations and Study Status
12	June 24, 2013	Contacts/Locations and Study Status
13	August 20, 2013	Study Status and Contacts/Locations
14	September 20, 2013	Contacts/Locations and Study Status
15	December 23, 2013	Outcome Measures, Study Status, Study Description, Contacts/Locations, Arms and Interventions and Study Identification
16	February 6, 2014	Study Status and Contacts/Locations
17	March 7, 2014	Contacts/Locations and Study Status
18	April 14, 2014	Study Status and Contacts/Locations
19	May 22, 2014	Study Status and Contacts/Locations
20	July 2, 2014	Study Status and Contacts/Locations
21	July 24, 2014	Contacts/Locations and Study Status
22	September 5, 2014	Recruitment Status, Contacts/Locations, Arms and Interventions, Study Status, Outcome Measures and Conditions
23	October 21, 2014	Study Status and Contacts/Locations
24	May 1, 2015	Contacts/Locations and Study Status
25	December 4, 2015	Study Status
26	January 20, 2016	Study Status
27	May 24, 2016	Study Status, Study Design and Eligibility
28	June 9, 2017	Contacts/Locations, Study Status, Oversight, Eligibility and Study Identification
29	October 24, 2017	Study Status
	Results Submission Events
December 18, 2017		Returned after QC review: January 18, 2018
30	January 29, 2018	Study Status, Outcome Measures, More Information, References, Arms and Interventions, Adverse Events, Baseline Characteristics, Participant Flow, Contacts/Locations and Study Description
31	June 25, 2018	Study Status
32	October 9, 2018	Study Status
33	January 7, 2019	Study Status
34	May 6, 2019	Study Status
35	June 26, 2019	Recruitment Status, Study Status and IPDSharing
36	March 2, 2020	Outcome Measures, Adverse Events, Participant Flow, Baseline Characteristics, Study Status, More Information, IPDSharing, Document Section, Eligibility, Arms and Interventions, Conditions, Study Description and Study Identification

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	GS-US-312-0115
Brief Title:	A Randomized, Double-Blind and Placebo-Controlled Study of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela)
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
Secondary IDs:	2011-006292-20 [EudraCT Number]

Study Status


Record Verification:	May 2019
Overall Status:	Active, not recruiting
Study Start:	June 26, 2012
Primary Completion:	October 7, 2015 [Actual]
Study Completion:	May 2019 [Anticipated]

First Submitted:	March 27, 2012
First Submitted that Met QC Criteria:	March 30, 2012
First Posted:	April 3, 2012 [Estimate]

Results First Submitted:	December 18, 2017
Results First Submitted that Met QC Criteria:	January 29, 2018
Results First Posted:	February 27, 2018 [Actual]

Certification/Extension First Submitted:	May 24, 2016
Certification/Extension First Submitted that Met QC Criteria:	May 24, 2016
Certification/Extension First Posted:	June 6, 2016 [Estimate]

Last Update Submitted that Met QC Criteria:	May 6, 2019
Last Update Posted:	May 14, 2019 [Actual]

Sponsor/Collaborators


Sponsor:	Gilead Sciences
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


Brief Summary:	The primary objective of this study is to evaluate the effect of the addition of idelalisib (IDL [GS-1101, Zydelig®]) to bendamustine + rituximab (BR) on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL)
Detailed Description:

Conditions


Conditions:	Chronic Lymphocytic Leukemia
Keywords:	Zydelig CLL CAL 101 CAL-101 GS 1101 GS-1101 PI3K Rituxan Rituximab Bendamustine Leukemia idelalisib

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Triple (Participant, Care Provider, Investigator)
Allocation:	Randomized
Enrollment:	416 [Actual]

Arms and Interventions

Arms

Assigned Interventions

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
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

[See Results Section.]


Primary Outcome Measures:
1.	Progression-Free Survival [ Time Frame: Up to 45 months ] 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
Secondary Outcome Measures:
1.	Overall Response Rate (ORR) [ Time Frame: Up to 45 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.
2.	Lymph Node Response Rate [ Time Frame: Up to 45 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.
3.	Overall Survival [ Time Frame: Up to 47 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.
4.	Complete Response Rate [ Time Frame: Up to 40 months ] Complete response (CR) rate was defined as the percentage of participants who achieved a CR.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	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/Locations


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

IPDSharing


Plan to Share IPD:

References


Citations:	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
	Zelenetz AD, Barrientos JC, Brown JR, Coiffier B, Delgado J, Egyed M, Ghia P, Illes A, Jurczak W, Marlton P, Montillo M, Morschhauser F, Pristupa AS, Robak T, Sharman JP, Simpson D, Smolej L, Tausch E, Adewoye AH, Dreiling LK, Kim Y, Stilgenbauer S, Hillmen P. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017 Mar;18(3):297-311. doi: 10.1016/S1470-2045(16)30671-4. Epub 2017 Jan 28. PubMed 28139405
Links:
Available IPD/Information:

Participant Flow

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

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

Reason Not Completed

Ongoing in Study

Adverse Event

Withdrawal by Subject

Physician Decision

Other

Noncompliance with Study Drug

Other Anticancer/Experimental Therapy

Lost to Follow-up

[1]	Completed = reached primary efficacy endpoint (progressive disease or death)

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 Number of Baseline Participants		207	209	416
Baseline Analysis Population Description
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 22.71%	53 25.36%	100 24.04%
	Male	160 77.29%	156 74.64%	316 75.96%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	207 Participants	209 Participants	416 Participants
White		187 90.34%	190 90.91%	377 90.62%
Black or African American		6 2.9%	4 1.91%	10 2.4%
Asian		2 0.97%	1 0.48%	3 0.72%
Other		2 0.97%	2 0.96%	4 0.96%
Not Permitted		10 4.83%	12 5.74%	22 5.29%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	207 Participants	209 Participants	416 Participants
Hispanic or Latino		4 1.93%	5 2.39%	9 2.16%
Not Hispanic or Latino		191 92.27%	188 89.95%	379 91.11%
Not Permitted		12 5.8%	15 7.18%	27 6.49%
Missing		0 0%	1 0.48%	1 0.24%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	207 Participants	209 Participants	416 Participants
Romania		5 2.42%	6 2.87%	11 2.64%
Hungary		24 11.59%	20 9.57%	44 10.58%
United States		37 17.87%	33 15.79%	70 16.83%
Czechia		9 4.35%	5 2.39%	14 3.37%
United Kingdom		27 13.04%	29 13.88%	56 13.46%
Portugal		1 0.48%	4 1.91%	5 1.2%
Russia		22 10.63%	14 6.7%	36 8.65%
Spain		14 6.76%	18 8.61%	32 7.69%
Greece		1 0.48%	1 0.48%	2 0.48%
Canada		0 0%	3 1.44%	3 0.72%
Turkey		6 2.9%	6 2.87%	12 2.88%
Belgium		3 1.45%	7 3.35%	10 2.4%
Ireland		1 0.48%	1 0.48%	2 0.48%
Poland		17 8.21%	22 10.53%	39 9.38%
Italy		10 4.83%	7 3.35%	17 4.09%
Australia		8 3.86%	8 3.83%	16 3.85%
France		13 6.28%	14 6.7%	27 6.49%
Croatia		5 2.42%	9 4.31%	14 3.37%
New Zealand		4 1.93%	2 0.96%	6 1.44%

Outcome Measures

1. Primary Outcome:

Title

Progression-Free Survival

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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set


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)
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)

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)

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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set


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)
Overall Number of Participants Analyzed	207	209
Number (95% Confidence Interval) Unit of Measure: percentage of participants	70.0(63.3 to 76.2)	45.0(38.1 to 52.0)

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

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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set


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)
Overall Number of Participants Analyzed	207	209
Number (95% Confidence Interval) Unit of Measure: percentage of particpants	96.9(93.3 to 98.8)	60.9(53.7 to 67.8)

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

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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set


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)
Overall Number of Participants Analyzed	207	209
Median (95% Confidence Interval) Unit of Measure: months	NA(NA to NA)^[1]	31.6(21.3 to NA)^[1]

[1]	NA Explanation: Not reached

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

Description

Complete response (CR) rate was defined as the percentage of participants who achieved a CR.

Time Frame

Up to 40 months

Outcome Measure Data

Analysis Population Description

ITT Analysis Set


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)
Overall Number of Participants Analyzed	207	209
Number (95% Confidence Interval) Unit of Measure: percentage of participants	1.4(0.3 to 4.2)	0(0 to 1.7)

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]

Adverse Events


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
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	/	/
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 ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
Anaemia ^{† A}	6 / 207 (2.9%)	5 / 209 (2.39%)
Autoimmune haemolytic anaemia ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
Febrile neutropenia ^{† A}	43 / 207 (20.77%)	10 / 209 (4.78%)
Haemolytic anaemia ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Histiocytosis haematophagic ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Immune thrombocytopenic purpura ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Lymphadenopathy ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Neutropenia ^{† A}	9 / 207 (4.35%)	3 / 209 (1.44%)
Thrombocytopenia ^{† A}	3 / 207 (1.45%)	0 / 209 (0%)
Thrombotic thrombocytopenic purpura ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Cardiac disorders
Acute myocardial infarction ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
Atrial fibrillation ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Cardiac arrest ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Cardiac failure ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Cardiac failure congestive ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Left ventricular dysfunction ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Pericardial effusion ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Supraventricular extrasystoles ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Eye disorders
Retinal detachment ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Vision blurred ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Gastrointestinal disorders
Abdominal hernia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Abdominal pain ^{† A}	4 / 207 (1.93%)	2 / 209 (0.96%)
Ascites ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
Colitis ^{† A}	4 / 207 (1.93%)	1 / 209 (0.48%)
Colitis ulcerative ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Constipation ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Diarrhoea ^{† A}	12 / 207 (5.8%)	1 / 209 (0.48%)
Diverticular perforation ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Enterovesical fistula ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Gastric haemorrhage ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Gastrointestinal haemorrhage ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Nausea ^{† A}	1 / 207 (0.48%)	2 / 209 (0.96%)
Neutropenic colitis ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pancreatitis ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Pancreatitis acute ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Vomiting ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
General disorders
Asthenia ^{† A}	1 / 207 (0.48%)	2 / 209 (0.96%)
Chest pain ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Chills ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Fatigue ^{† A}	2 / 207 (0.97%)	2 / 209 (0.96%)
General physical health deterioration ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Malaise ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Multiple organ dysfunction syndrome ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Necrosis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Pyrexia ^{† A}	25 / 207 (12.08%)	11 / 209 (5.26%)
Hepatobiliary disorders
Bile duct obstruction ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Biliary fistula ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cholangitis ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Cholecystitis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cholelithiasis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hepatic failure ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Hepatitis toxic ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hepatocellular injury ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Hepatotoxicity ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Immune system disorders
Drug hypersensitivity ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hypersensitivity ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Infections and infestations
Aspergillus infection ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Bacteraemia ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Bacterial sepsis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Brain abscess ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Bronchitis ^{† A}	1 / 207 (0.48%)	5 / 209 (2.39%)
Bronchopulmonary aspergillosis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Campylobacter gastroenteritis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cellulitis ^{† A}	4 / 207 (1.93%)	0 / 209 (0%)
Clostridium difficile infection ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Conjunctivitis bacterial ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cystitis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cytomegalovirus chorioretinitis ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Cytomegalovirus colitis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cytomegalovirus enteritis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cytomegalovirus infection ^{† A}	2 / 207 (0.97%)	1 / 209 (0.48%)
Cytomegalovirus viraemia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Device related infection ^{† A}	2 / 207 (0.97%)	1 / 209 (0.48%)
Ecthyma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Escherichia sepsis ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Eye infection toxoplasmal ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Fungal infection ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Gastroenteritis ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Gastroenteritis cryptosporidial ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
H1N1 influenza ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Haemophilus infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Herpes simplex ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Herpes zoster ^{† A}	4 / 207 (1.93%)	1 / 209 (0.48%)
Human herpesvirus 6 infection ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Impetigo ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Influenza ^{† A}	2 / 207 (0.97%)	1 / 209 (0.48%)
Lower respiratory tract infection ^{† A}	6 / 207 (2.9%)	5 / 209 (2.39%)
Lower respiratory tract infection fungal ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Lung infection ^{† A}	0 / 207 (0%)	3 / 209 (1.44%)
Meningitis bacterial ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Meningitis enteroviral ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Neutropenic infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Neutropenic sepsis ^{† A}	3 / 207 (1.45%)	6 / 209 (2.87%)
Ophthalmic herpes zoster ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Oral herpes ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Oropharyngitis fungal ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Otitis externa ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Otitis media ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
Perineal infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Pharyngeal abscess ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pneumocystis jirovecii infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Pneumocystis jirovecii pneumonia ^{† A}	3 / 207 (1.45%)	0 / 209 (0%)
Pneumonia ^{† A}	36 / 207 (17.39%)	16 / 209 (7.66%)
Pneumonia bacterial ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pneumonia cytomegaloviral ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Pneumonia pseudomonal ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Pneumonia viral ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pulmonary mycosis ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pulmonary sepsis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Reiter's syndrome ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Respiratory syncytial virus infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Respiratory tract infection ^{† A}	3 / 207 (1.45%)	5 / 209 (2.39%)
Rhinovirus infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Sepsis ^{† A}	10 / 207 (4.83%)	4 / 209 (1.91%)
Septic shock ^{† A}	5 / 207 (2.42%)	1 / 209 (0.48%)
Sinusitis ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Soft tissue infection ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Tonsillitis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Tuberculosis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Upper respiratory tract infection ^{† A}	0 / 207 (0%)	4 / 209 (1.91%)
Upper respiratory tract infection bacterial ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Urinary tract infection ^{† A}	5 / 207 (2.42%)	3 / 209 (1.44%)
Urinary tract infection bacterial ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Urosepsis ^{† A}	2 / 207 (0.97%)	1 / 209 (0.48%)
Viral infection ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Injury, poisoning and procedural complications
Ankle fracture ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Cervical vertebral fracture ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Eye injury ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Femur fracture ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Infusion related reaction ^{† A}	2 / 207 (0.97%)	3 / 209 (1.44%)
Periprosthetic fracture ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Wrist fracture ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Investigations
Alanine aminotransferase increased ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Aspartate aminotransferase increased ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Blood creatinine increased ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Blood lactate dehydrogenase increased ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
International normalised ratio increased ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Neutrophil count decreased ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Polyomavirus test positive ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Transaminases increased ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Metabolism and nutrition disorders
Cachexia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Decreased appetite ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Dehydration ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Diabetes mellitus inadequate control ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hypercalcaemia ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Hyperglycaemia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hypoalbuminaemia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hypokalaemia ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Hyponatraemia ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Malnutrition ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Tumour lysis syndrome ^{† A}	3 / 207 (1.45%)	2 / 209 (0.96%)
Musculoskeletal and connective tissue disorders
Arthralgia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Chondritis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Chondrocalcinosis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Myalgia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Polyarthritis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon ^{† A}	0 / 207 (0%)	2 / 209 (0.96%)
Basal cell carcinoma ^{† A}	3 / 207 (1.45%)	0 / 209 (0%)
Bladder cancer ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Bowen's disease ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Chronic lymphocytic leukaemia ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Gastric cancer ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Leiomyosarcoma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Lip squamous cell carcinoma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Lung adenocarcinoma ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Lung neoplasm malignant ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Malignant melanoma ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Meningioma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Myelodysplastic syndrome ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Nasopharyngeal cancer ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Oesophageal carcinoma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Prostate cancer ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Rectal adenocarcinoma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Squamous cell carcinoma ^{† A}	1 / 207 (0.48%)	5 / 209 (2.39%)
Squamous cell carcinoma of lung ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Squamous cell carcinoma of skin ^{† A}	3 / 207 (1.45%)	2 / 209 (0.96%)
T-cell lymphoma ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Transitional cell carcinoma ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Nervous system disorders
Cerebral haemorrhage ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Dizziness ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Headache ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Ischaemic stroke ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Post herpetic neuralgia ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Seizure ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Syncope ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Psychiatric disorders
Anxiety ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Confusional state ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Delusion ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Mental status changes ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Mood swings ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Panic attack ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Personality change ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Renal and urinary disorders
Acute kidney injury ^{† A}	1 / 207 (0.48%)	1 / 209 (0.48%)
Calculus urinary ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Haematuria ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Renal colic ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Renal failure ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Urinary incontinence ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Reproductive system and breast disorders
Cervical polyp ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Bronchial hyperreactivity ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Chronic obstructive pulmonary disease ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Cough ^{† A}	4 / 207 (1.93%)	2 / 209 (0.96%)
Dyspnoea ^{† A}	3 / 207 (1.45%)	3 / 209 (1.44%)
Epistaxis ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Hypoxia ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Lung disorder ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pleural effusion ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Pneumonia aspiration ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Pneumonitis ^{† A}	4 / 207 (1.93%)	0 / 209 (0%)
Pneumothorax ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Pulmonary embolism ^{† A}	2 / 207 (0.97%)	5 / 209 (2.39%)
Pulmonary pain ^{† A}	0 / 207 (0%)	1 / 209 (0.48%)
Respiratory distress ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Respiratory failure ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Skin and subcutaneous tissue disorders
Dermatitis atopic ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Dermatitis exfoliative ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Drug reaction with eosinophilia and systemic symptoms ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Rash macular ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Rash maculo-papular ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Stevens-Johnson syndrome ^{† A}	2 / 207 (0.97%)	0 / 209 (0%)
Vascular disorders
Deep vein thrombosis ^{† A}	1 / 207 (0.48%)	0 / 209 (0%)
Hypotension ^{† A}	2 / 207 (0.97%)	2 / 209 (0.96%)
†Indicates events were collected by systematic assessment. ATerm from vocabulary, MedDRA (19.0)
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 ^{† A}	53 / 207 (25.6%)	47 / 209 (22.49%)
Leukopenia ^{† A}	17 / 207 (8.21%)	10 / 209 (4.78%)
Neutropenia ^{† A}	129 / 207 (62.32%)	113 / 209 (54.07%)
Thrombocytopenia ^{† A}	41 / 207 (19.81%)	46 / 209 (22.01%)
Gastrointestinal disorders
Abdominal pain ^{† A}	18 / 207 (8.7%)	12 / 209 (5.74%)
Constipation ^{† A}	32 / 207 (15.46%)	35 / 209 (16.75%)
Diarrhoea ^{† A}	81 / 207 (39.13%)	47 / 209 (22.49%)
Dyspepsia ^{† A}	13 / 207 (6.28%)	8 / 209 (3.83%)
Nausea ^{† A}	56 / 207 (27.05%)	72 / 209 (34.45%)
Vomiting ^{† A}	34 / 207 (16.43%)	31 / 209 (14.83%)
General disorders
Asthenia ^{† A}	22 / 207 (10.63%)	20 / 209 (9.57%)
Chills ^{† A}	21 / 207 (10.14%)	13 / 209 (6.22%)
Fatigue ^{† A}	42 / 207 (20.29%)	52 / 209 (24.88%)
Oedema peripheral ^{† A}	16 / 207 (7.73%)	18 / 209 (8.61%)
Pyrexia ^{† A}	78 / 207 (37.68%)	55 / 209 (26.32%)
Immune system disorders
Hypogammaglobulinaemia ^{† A}	12 / 207 (5.8%)	10 / 209 (4.78%)
Infections and infestations
Bronchitis ^{† A}	15 / 207 (7.25%)	8 / 209 (3.83%)
Lower respiratory tract infection ^{† A}	12 / 207 (5.8%)	10 / 209 (4.78%)
Nasopharyngitis ^{† A}	15 / 207 (7.25%)	11 / 209 (5.26%)
Pneumonia ^{† A}	25 / 207 (12.08%)	12 / 209 (5.74%)
Respiratory tract infection ^{† A}	6 / 207 (2.9%)	11 / 209 (5.26%)
Sinusitis ^{† A}	16 / 207 (7.73%)	13 / 209 (6.22%)
Upper respiratory tract infection ^{† A}	36 / 207 (17.39%)	21 / 209 (10.05%)
Injury, poisoning and procedural complications
Infusion related reaction ^{† A}	29 / 207 (14.01%)	46 / 209 (22.01%)
Investigations
Alanine aminotransferase increased ^{† A}	32 / 207 (15.46%)	3 / 209 (1.44%)
Aspartate aminotransferase increased ^{† A}	19 / 207 (9.18%)	2 / 209 (0.96%)
Weight decreased ^{† A}	21 / 207 (10.14%)	12 / 209 (5.74%)
Metabolism and nutrition disorders
Decreased appetite ^{† A}	22 / 207 (10.63%)	15 / 209 (7.18%)
Hypokalaemia ^{† A}	19 / 207 (9.18%)	16 / 209 (7.66%)
Musculoskeletal and connective tissue disorders
Arthralgia ^{† A}	25 / 207 (12.08%)	16 / 209 (7.66%)
Back pain ^{† A}	15 / 207 (7.25%)	15 / 209 (7.18%)
Nervous system disorders
Headache ^{† A}	20 / 207 (9.66%)	21 / 209 (10.05%)
Psychiatric disorders
Anxiety ^{† A}	6 / 207 (2.9%)	12 / 209 (5.74%)
Insomnia ^{† A}	19 / 207 (9.18%)	13 / 209 (6.22%)
Respiratory, thoracic and mediastinal disorders
Cough ^{† A}	47 / 207 (22.71%)	47 / 209 (22.49%)
Dyspnoea ^{† A}	20 / 207 (9.66%)	26 / 209 (12.44%)
Oropharyngeal pain ^{† A}	10 / 207 (4.83%)	14 / 209 (6.7%)
Productive cough ^{† A}	17 / 207 (8.21%)	12 / 209 (5.74%)
Skin and subcutaneous tissue disorders
Night sweats ^{† A}	17 / 207 (8.21%)	8 / 209 (3.83%)
Pruritus ^{† A}	16 / 207 (7.73%)	12 / 209 (5.74%)
Rash ^{† A}	35 / 207 (16.91%)	28 / 209 (13.4%)
Vascular disorders
Hypertension ^{† A}	11 / 207 (5.31%)	5 / 209 (2.39%)
Hypotension ^{† A}	14 / 207 (6.76%)	12 / 209 (5.74%)
†Indicates events were collected by systematic assessment. ATerm from vocabulary, MedDRA (19.0)

Limitations and Caveats


[Not specified]

More Information


Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study. There IS an agreement between the Principal Investigator 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/Official Title:	Clinical Trial Disclosures
Organization:	Gilead Sciences
Phone:
Email:	ClinicalTrialDisclosures@gilead.com